Bio

Bio


Michelle Odden, PhD, is an Associate Professor of Epidemiology in the Department of Health Research and Policy. Her research aims to improve our understanding of the optimal preventive strategies for chronic disease in older adults, particularly those who have been underrepresented in research including the very old, frail, and racial/ethnic minorities. Her work has focused on prevention of cardiovascular and kidney outcomes, as well as preservation of physical and cognitive function in older adults. She is also strongly interested in epidemiological and statistical methods to reduce biases in observational studies. Dr. Odden came to Stanford from Oregon State University, where she helped build the new College of Public Health and Human Sciences. She completed her Ph.D. in Epidemiology from the University of California, Berkeley (2009), a postdoctoral fellowship at the University of California, San Francisco in Primary Care Research (2011).

Academic Appointments


Professional Education


  • MS, University of California, Berkeley, Epidemiology (2006)
  • PhD, University of California, Berkeley, Epidemiology (2009)
  • Postdoctoral Fellowship, University of California, San Francisco, Primary Care Research (2011)

Teaching

2018-19 Courses


Stanford Advisees


Publications

All Publications


  • Validation of the REGARDS Severe Sepsis Risk Score. Journal of clinical medicine Wang, H. E., Donnelly, J. P., Yende, S., Levitan, E. B., Shapiro, N. I., Dai, Y., Zhao, H., Heiss, G., Odden, M., Newman, A., Safford, M. 2018; 7 (12)

    Abstract

    There are no validated systems for characterizing long-term risk of severe sepsis in community-dwelling adults. We tested the ability of the REasons for Geographic and Racial Differences in Stroke-Severe Sepsis Risk Score (REGARDS-SSRS) to predict 10-year severe sepsis risk in separate cohorts of community-dwelling adults. We internally tested the REGARDS-SSRS on the REGARDS-Medicare subcohort. We then externally validated the REGARDS-SSRS using (1) the Cardiovascular Health Study (CHS) and (2) the Atherosclerosis Risk in Communities (ARIC) cohorts. Participants included community-dwelling adults: REGARDS-Medicare, age ?65 years, n = 9522; CHS, age ?65 years, n = 5888; ARIC, age 45?64 years, n = 11,584. The primary exposure was 10-year severe sepsis risk, predicted by the REGARDS-SSRS from participant sociodemographics, health behaviors, chronic medical conditions and select biomarkers. The primary outcome was first severe sepsis hospitalizations, defined as the concurrent presence of ICD-9 discharge diagnoses for a serious infection and organ dysfunction. Median SSRS in the cohorts were: REGARDS-Medicare 11 points (IQR 7?16), CHS 10 (IQR 6?15), ARIC 7 (IQR 5?10). Severe sepsis incidence rates were: REGARDS-Medicare 30.7 per 1000 person-years (95% CI: 29.2?32.2); CHS 11.9 (10.9?12.9); ARIC 6.8 (6.3?7.3). SSRS discrimination for first severe sepsis events were: REGARDS-Medicare C-statistic 0.704 (95% CI: 0.691?0.718), CHS 0.696 (0.675?0.716), ARIC 0.697 (0.677?0.716). The REGARDS-SRSS may potentially play a role in identifying community-dwelling adults at high severe sepsis risk.

    View details for PubMedID 30544923

  • Potential Cardiovascular Disease Events Prevented with Adoption of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline. Circulation Bress, A. P., Colantonio, L. D., Cooper, R., Kramer, H., Booth Iii, J. N., Odden, M. C., Bibbins-Domingo, K., Shimbo, D., Whelton, P. K., Levitan, E. B., Howard, G., Bellows, B. K., Kleindorfer, D., Safford, M. M., Muntner, P., Moran, A. E. 2018

    Abstract

    BACKGROUND: Over 10 years, achieving and maintaining 2017 ACC/AHA guideline goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), and 1.4 million (UR, 0.6-2.0 million) cardiovascular disease (CVD) events compared with maintaining current blood pressure (BP) levels, achieving 2003 Seventh Joint National Committee Report goals, and achieving 2014 Eighth Joint National Committee goals, respectively. We estimated the number of cardiovascular disease events prevented and treatment-related serious adverse events incurred over 10 years among US adults with hypertension by achieving 2017 ACC/AHA guideline-recommended BP goals compared with (1) current BP levels, (2) achieving 2003 Seventh Joint National Committee Report BP goals, and (3) achieving 2014 Eighth Joint National Committee panel member report BP goals.METHODS: US adults aged ?45 years with an indication for BP treatment were grouped according to recommendations for antihypertensive drug therapy in the 2017 ACC/AHA guideline, 2003 Seventh Joint National Committee Report, and 2014 Eighth Joint National Committee. Population sizes were estimated from the 2011 to 2014 National Health and Nutrition Examination Surveys. Rates for fatal and nonfatal CVD events (stroke, coronary heart disease, or heart failure) were estimated from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, weighted to the US population. CVD risk reductions with treatment to BP goals and risk for serious adverse events were obtained from meta-analyses of BP-lowering trials. CVD events prevented and treatment-related nonfatal serious adverse events over 10 years were calculated. Uncertainty surrounding main data inputs was expressed in uncertainty ranges (UR).RESULTS: Over ten years, achieving and maintaining 2017 ACC/AHA guideline goals compared with current BP levels, achieving 2003 Seventh Joint National Committee Report goals, or achieving 2014 Eighth Joint National Committee goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), or 1.4 million (UR, 0.6-2.0 million) CVD events, respectively. Compared with current BP levels, achieving and maintaining 2017 goals could prevent 71.9 (UR, 26.6-122.3) CVD events per 1000 treated. Achieving 2017 guideline BP goals compared with current BP levels could also lead to nearly 3.3 million more serious adverse events over 10 years (UR, 2.2-4.4 million).CONCLUSIONS: Achieving and maintaining 2017 ACC/AHA BP goals could prevent a greater number of CVD events than achieving 2003 Seventh Joint National Committee Report or 2014 Eighth Joint National Committee BP goals but could also lead to more serious adverse events.

    View details for PubMedID 30586736

  • Trajectories of Nonagenarian Health: Gender, Age, and Period Effects. American journal of epidemiology Odden, M. C., Koh, W. J., Arnold, A. M., Rawlings, A. M., Psaty, B. M., Newman, A. B. 2018

    Abstract

    The US population aged 90 years and older is growing rapidly and there are limited data on their health. The Cardiovascular Health Study is a prospective study of black and white adults ?65 years recruited in two waves (1989-90 and 1992-93) from Medicare eligibility lists in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. We created a synthetic cohort of the 1,889 participants who had reached age 90 at baseline or during follow-up through July 16th, 2015. Participants entered the cohort at 90 years and we evaluated their changes in health after age 90 (median [IQR] follow-up: 3 [1.3-5] years). Measures of health included cardiovascular events, cognitive function, depressive symptoms, prescription medications, self-rated health, and measures of functional status. The mortality rate was high: 19.0 (95% CI: 17.8, 20.3) per 100 person-years in women and 20.9 (95% CI: 19.2, 22.8) in men. Cognitive function and all measures of functional status declined with age; these changes were similar by gender. When we isolated period effects, we found that medications use increased over time. These estimates can help inform future research and health care systems to meet the needs of this growing population.

    View details for PubMedID 30407481

  • Formulating and Answering High-Impact Causal Questions in Physiologic Childbirth Science: Concepts and Assumptions JOURNAL OF MIDWIFERY & WOMENS HEALTH Snowden, J. M., Tilden, E. L., Odden, M. C. 2018; 63 (6): 721?30

    Abstract

    In this article, we conclude our 3-part series by focusing on several concepts that have proven useful for formulating causal questions and inferring causal effects. The process of causal inference is of key importance for physiologic childbirth science, so each concept is grounded in content related to women at low risk for perinatal complications. A prerequisite to causal inference is determining that the question of interest is causal rather than descriptive or predictive. Another critical step in defining a high-impact causal question is assessing the state of existing research for evidence of causality. We introduce 2 causal frameworks that are useful for this undertaking, Hill's causal considerations and the sufficient-component cause model. We then provide 3 steps to aid perinatal researchers in inferring causal effects in a given study. First, the researcher should formulate a rigorous and clear causal question. We introduce an example of epidural analgesia and labor progression to demonstrate this process, including the central role of temporality. Next, the researcher should assess the suitability of the given data set to answer this causal question. In randomized controlled trials, data are collected with the express purpose of answering the causal question. Investigators using observational data should also ensure that their chosen causal question is answerable with the available data. Finally, investigators should design an analysis plan that targets the causal question of interest. Some data structures (eg, time-dependent confounding by labor progress when estimating the effect of epidural analgesia on postpartum hemorrhage) require specific analytical tools to control for bias and estimate causal effects. The assumptions of consistency, exchangeability, and positivity may be especially useful in carrying out these steps. Drawing on appropriate causal concepts and considering relevant assumptions strengthens our confidence that research has reduced the likelihood of alternative explanations (eg bias, chance) and estimated a causal effect.

    View details for DOI 10.1111/jmwh.12868

    View details for Web of Science ID 000450030100011

    View details for PubMedID 29883521

  • Serial circulating omega 3 polyunsaturated fatty acids and healthy ageing among older adults in the Cardiovascular Health Study: prospective cohort study BMJ-BRITISH MEDICAL JOURNAL Lai, H. M., Otto, M., Lemaitre, R. N., McKnight, B., Song, X., King, I. B., Chaves, P. M., Odden, M. C., Newman, A. B., Siscovick, D. S., Mozaffarian, D. 2018; 363: k4067

    Abstract

    To determine the longitudinal association between serial biomarker measures of circulating omega 3 polyunsaturated fatty acid (n3-PUFA) levels and healthy ageing.Prospective cohort study.Four communities in the United States (Cardiovascular Health Study) from 1992 to 2015.2622 adults with a mean (SD) age of 74.4 (4.8) and with successful healthy ageing at baseline in 1992-93.Cumulative levels of plasma phospholipid n3-PUFAs were measured using gas chromatography in 1992-93, 1998-99, and 2005-06, expressed as percentage of total fatty acids, including ?-linolenic acid from plants and eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid from seafoood.Healthy ageing defined as survival without chronic diseases (ie, cardiovascular disease, cancer, lung disease, and severe chronic kidney disease), the absence of cognitive and physical dysfunction, or death from other causes not part of the healthy ageing outcome after age 65. Events were centrally adjudicated or determined from medical records and diagnostic tests.Higher levels of long chain n3-PUFAs were associated with an 18% lower risk (95% confidence interval 7% to 28%) of unhealthy ageing per interquintile range after multivariable adjustments with time-varying exposure and covariates. Individually, higher eicosapentaenoic acid and docosapentaenoic acid (but not docosahexaenoic acid) levels were associated with a lower risk: 15% (6% to 23%) and 16% (6% to 25%), respectively. ?-linolenic acid from plants was not noticeably associated with unhealthy ageing (hazard ratio 0.92, 95% confidence interval 0.83 to 1.02).In older adults, a higher cumulative level of serially measured circulating n3-PUFAs from seafood (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid), eicosapentaenoic acid, and docosapentaenoic acid (but not docosahexaenoic acid from seafood or ?-linolenic acid from plants) was associated with a higher likelihood of healthy ageing. These findings support guidelines for increased dietary consumption of n3-PUFAs in older adults.

    View details for PubMedID 30333104

  • Development, Construct Validity, and Predictive Validity of a Continuous Frailty Scale: Results From 2 Large US Cohorts AMERICAN JOURNAL OF EPIDEMIOLOGY Wu, C., Geldhof, G., Xue, Q., Kim, D. H., Newman, A. B., Odden, M. C. 2018; 187 (8): 1752?62

    Abstract

    Frailty is an age-related clinical syndrome of decreased resilience to stressors. Among numerous assessments of frailty, the frailty phenotype (FP) scale, proposed by Fried and colleagues has been the most widely used one. We aimed to develop a continuous frailty scale that may overcome limitations facing the categorical FP scale and to evaluate its construct validity, predictive validity, and measurement properties. Data were from the Cardiovascular Health Study (N = 4243) and Health and Retirement Study (N = 7600). Frailty was conceptualized as a continuous construct, measured by five measures used in FP scale: gait speed, grip strength, exhaustion, physical activity, and weight loss. We used confirmatory factor analysis to investigate the relationship between five indicators and the latent frailty construct. We examined the association of the continuous frailty scale with mortality and disability. The unidimensional model fit the data satisfactorily; similar factor structure was observed across two cohorts. Gait speed and weight loss were the strongest and weakest indicators, respectively; grip strength, exhaustion, and physical activity had similar strength in measuring frailty. In each cohort, the continuous frailty scale was strongly associated with mortality and disability and persisted to be associated with outcomes among robust and prefrail persons classified by the FP scale.

    View details for PubMedID 29688247

  • Index of Healthy Aging in Chinese Older Adults: China Health and Retirement Longitudinal Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Wu, C., Newman, A. B., Dong, B., Odden, M. C. 2018; 66 (7): 1303?10

    Abstract

    To characterize the distribution of an index of healthy aging-the Chinese Healthy Aging Index (CHAI)-in Chinese adults aged 60 and older according to sociodemographic characteristics and geographic region and to examine the association between the CHAI and mortality, disability, and functional limitation over 4 years.Nationally representative cohort study.China Health and Retirement Longitudinal Study.Chinese adults aged 60 and older (N=3,740).Six CHAI components (systolic blood pressure, peak expiratory flow, Telephone Interview for Cognitive Status, estimated glomerular filtration rate, fasting glucose, C-reactive protein) were scored 0 (healthiest), 1, and 2 (unhealthiest) according to sex-specific tertiles or clinically relevant cut-points and summed to construct the CHAI (range 0-12).Mean CHAI score was 5.6; 5.7% had a score of 0 to 2 (healthiest), 23.0% a score of 3 or 4, 37.5% a score of 5 or 6, and 33.8% a score of 7 to 12 (unhealthiest). Participants who were younger, more educated, and married were much more likely to have an ideal CHAI profile (score 0-2). Age-adjusted prevalence of an ideal CHAI profile ranged from 1.7% in the south to 8.1% in the north. After multivariable adjustment, persons with a CHAI score of 3 to 12 had substantially higher odds of mortality, disability, and functional limitation than those with a score of 0 to 2. The CHAI further stratified outcomes for persons with no clinically recognizable comorbidities.Substantial variation exists in the CHAI according to sociodemographic characteristics and geographic regions. The CHAI could identify Chinese elderly adults with low risk of adverse outcomes and provide incremental value for risk prediction beyond clinically diagnosed comorbidities.

    View details for PubMedID 29684252

  • Racial/ethnic heterogeneity in associations of blood pressure and incident cardiovascular disease by functional status in a prospective cohort: the Multi-Ethnic Study of Atherosclerosis BMJ OPEN Kaiser, P., Peralta, C. A., Kronmal, R., Shlipak, M. G., Psaty, B. M., Odden, M. C. 2018; 8 (2): e017746

    Abstract

    Research has demonstrated that the association between high blood pressure and outcomes is attenuated among older adults with functional limitations, compared with healthier elders. However, it is not known whether these patterns vary by racial/ethnic group. We evaluated race/ethnicity-specific patterns of effect modification in the association between blood pressure and incident cardiovascular disease (CVD) by functional status.We used data from the Multi-Ethnic Study of Atherosclerosis (2002-2004, with an average of 8.8 years of follow-up for incident CVD). We assessed effect modification of systolic blood pressure and cardiovascular outcomes by self-reported physical limitations and by age.The study included 6117 participants (aged 46 to 87; 40% white, 27% black, 22% Hispanic and 12% Chinese) who did not have CVD at the second study examination (when self-reported physical limitations were assessed).Incident CVD was defined as an incident myocardial infarction, coronary revascularisation, resuscitated cardiac arrest, angina, stroke (fatal or non-fatal) or death from CVD.We observed weaker associations between systolic blood pressure (SBP) and CVD among white adults with physical limitations (incident rate ratio (IRR) per 10?mm Hg higher SBP: 1.09 (95% CI 0.99 to 1.20)) than those without physical limitations (IRR 1.29 (1.19, 1.40); P value for interaction <0.01). We found a similar pattern among black adults. Poor precision among the estimates for Hispanic or Chinese participants limited the findings in these groups. The attenuated associations were consistent across both multiplicative and additive scales, though physical limitations showed clearer patterns than age on an additive scale.Attenuated associations between high blood pressure and incident CVD were observed for blacks and whites with poor function, though small sample sizes remain a limitation for identifying differences among Hispanic or Chinese participants. Identifying the characteristics that distinguish those in whom higher SBP is associated with less risk of morbidity or mortality may inform our understanding of the consequences of hypertension among older adults.

    View details for PubMedID 29476026

  • Longitudinal Blood Pressure Changes and Kidney Function Decline in Persons Without Chronic Kidney Disease: Findings From the MESA Study AMERICAN JOURNAL OF HYPERTENSION Judson, G. L., Rubinsky, A. D., Shlipak, M. G., Katz, R., Kramer, H., Jacobs, D. R., Odden, M. C., Peralta, C. A. 2018; 31 (5): 600?608

    Abstract

    While changes in blood pressure (BP) are independently associated with cardiovascular events, less is known about the association between changes in BP and subsequent changes in renal function in adults with an estimated glomerular filtration rate (eGFR) of >60 ml/min/1.73 m2.The present study included 3,920 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study who had ?2 BP measurements during the first 5 years of MESA and had eGFR measurements at both year 5 and 10. Change in BP was estimated as the annualized slope of BP between year 0 and 5 based on linear mixed models (mean number of measurements = 4.0). Participants were then grouped into 1 of 3 categories based on the distribution of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) change (top 20%, middle 21-79%, bottom 20%). We calculated eGFR from cystatin C (ml/min/1.73 m2), estimated annual change in eGFR (ml/min/1.73 m2/year), and defined rapid kidney function decline as a >30% decrease in eGFR from year 5 to 10. We used multivariable logistic regression adjusting for year 0 demographic and clinical characteristics, including eGFR and BP, to determine associations of BP change with rapid kidney function decline.Median age was 59 [interquartile range (IQR): 52, 67] and median eGFR at year 0 was 95.5 (IQR: 81.7, 105.9) ml/min/1.73 m2. Median SBP at year 0 was 111, 121, and 147 mm Hg for increasing, stable, and decreasing SBP change, respectively. Increasing SBP and widening PP change were each associated with higher odds of rapid kidney function decline compared with stable SBP and PP groups, respectively [odds ratio, OR 1.7 (95% confidence interval, CI 1.3, 2.4) for SBP; OR 1.4 (95% CI 1.1, 1.9) for PP]. Decreasing SBP was associated with rapid kidney function decline after adjusting for all covariates except for year 0 BP [OR 1.4 (95% CI 1.0, 1.8)], but this association was no longer statistically significant after adjustment for year 0 BP. There were no significant associations between DBP change and rapid decline in the fully adjusted models. Similar findings were seen with annual change in eGFR.Increasing SBP and widening PP over time were associated with greater risk for accelerated kidney function decline even at BP levels below established hypertension thresholds.

    View details for PubMedID 29036269

  • Comparing methods to address bias in observational data: statin use and cardiovascular events in a US cohort INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Kaiser, P., Arnold, A. M., Benkeser, D., Al Hazzouri, A., Hirsch, C. H., Psaty, B. M., Odden, M. C. 2018; 47 (1): 246?54

    Abstract

    The theoretical conditions under which causal estimates can be derived from observational data are challenging to achieve in the real world. Applied examples can help elucidate the practical limitations of methods to estimate randomized-controlled trial effects from observational data.We used six methods with varying design and analytic features to compare the 5-year risk of incident myocardial infarction among statin users and non-users, and used non-cardiovascular mortality as a negative control outcome. Design features included restriction to a statin-eligible population and new users only; analytic features included multivariable adjustment and propensity score matching.We used data from 5294 participants in the Cardiovascular Health Study from 1989 to 2004. For non-cardiovascular mortality, most methods produced protective estimates with confidence intervals that crossed the null. The hazard ratio (HR) was 0.92, 95% confidence interval: 0.58, 1.46 using propensity score matching among eligible new users. For myocardial infarction, all estimates were strongly protective; the propensity score-matched analysis among eligible new users resulted in a HR of 0.55 (0.29, 1.05)-a much stronger association than observed in randomized controlled trials.In designs that compare active treatment with non-treated participants to evaluate effectiveness, methods to address bias in observational data may be limited in real-world settings by residual bias.

    View details for PubMedID 29024975

  • Age, Race, and Gender Factors in Incident Disability JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Jacob, M. E., Marron, M. M., Boudreau, R. M., Odden, M. C., Arnold, A. M., Newman, A. B. 2018; 73 (2): 194?97

    Abstract

    Incident disability rates enable the comparison of risk across populations. Understanding these by age, sex, and race is important for planning for the care of older adults and targeting prevention.We calculated incident disability rates among older adults in the Cardiovascular Health Study, a study of 5,888 older adults aged ? 65 years over 6 years of follow-up. Disability was defined in the following two ways: (i) self-report of disability (severe difficulty or inability) in any of six Activities of Daily Living (ADL), and (ii) mobility difficulty (any difficulty walking half a mile or climbing 10 steps). Incident disability rates were calculated as events per 100 person years for age, gender, and race groups.The incidence of ADL disability, and mobility difficulty were 2.7 (2.5-2.8), and 9.8 (9.4-10.3) events per 100 person years. Women, older participants, and blacks had higher rates in both domains.Incidence rates are considerably different based on the domain examined as well as age, race, and gender composition of the population. Prevention efforts should focus on high risk populations and attempt to ameliorate factors that increase risk in these groups.

    View details for PubMedID 29045556

  • Outdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study. Environment international Wong, J. Y., Margolis, H. G., Machiela, M., Zhou, W., Odden, M. C., Psaty, B. M., Robbins, J., Jones, R. R., Rotter, J. I., Chanock, S. J., Rothman, N., Lan, Q., Lee, J. S. 2018; 116: 239?47

    Abstract

    Mosaic loss of chromosome Y (mLOY) can occur in a fraction of cells as men age, which is potentially linked to increased mortality risk. Smoking is related to mLOY; however, the contribution of air pollution is unclear.We investigated whether exposure to outdoor air pollution, age, and smoking were associated with mLOY.We analyzed baseline (1989-1993) blood samples from 933 men ?65?years of age from the prospective Cardiovascular Health Study. Particulate matter ?10??m (PM10), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone data were obtained from the U.S. EPA Aerometric Information Retrieval System for the year prior to baseline. Inverse-distance weighted air monitor data were used to estimate each participants' monthly residential exposure. mLOY was detected with standard methods using signal intensity (median log-R ratio (mLRR)) of the male-specific chromosome Y regions from Illumina array data. Linear regression models were used to evaluate relations between mean exposure in the prior year, age, smoking and continuous mLRR.Increased PM10 was associated with mLOY, namely decreased mLRR (p-trend?=?0.03). Compared with the lowest tertile (?28.5??g/m3), the middle (28.5-31.0??g/m3; ??=?-0.0044, p?=?0.09) and highest (?31??g/m3; ??=?-0.0054, p?=?0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (??=?-0.00035, p?=?0.06) and smoking pack-years (??=?-0.00011, p?=?1.4E-3) were associated with decreased mLRR, adjusted for each other and race/cohort. No significant associations were found for other pollutants.PM10 may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.

    View details for PubMedID 29698900

  • Prevalence and Correlates of Frailty Among Community-Dwelling Chinese Older Adults: The China Health and Retirement Longitudinal Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Wu, C., Smit, E., Xue, Q., Odden, M. C. 2018; 73 (1): 102?8

    Abstract

    Frailty is an age-related clinical syndrome of decreased resilience to stressors and is associated with numerous adverse outcomes. Although there is preponderance of literature on frailty in developed countries, limited investigations have been conducted in less developed regions including China-a country that has the world's largest aging population. We examined frailty prevalence in China by sociodemographics and geographic region, and investigated correlates of frailty.Participants were 5,301 adults aged ?60 years from the China Health and Retirement Longitudinal Study. Frailty was identified by the validated physical frailty phenotype (PFP) scale. We estimated frailty prevalence in the overall sample and by sociodemographics. We identified age-adjusted frailty prevalence by geographical region. Bivariate associations of frailty with health and function measures were evaluated by chi-squared test and analysis of variance.We found 7.0% of adults aged 60 years or older were frail. Frailty is more prevalent at advanced ages, among women, and persons with low education. Age-adjusted frailty prevalence ranged from 3.3% in the Southeast and the Northeast to 9.1% in the Northwest, and was more than 1.5 times higher in rural versus urban areas. Frail versus nonfrail persons had higher prevalence of comorbidities, falls, disability, and functional limitation.We demonstrated the utility of the PFP scale in identifying frail Chinese elders, and found substantial sociodemographic and regional disparities in frailty prevalence. The PFP scale may be incorporated into clinical practice in China to identify the most vulnerable elders to reduce morbidity, prevent disability, and enable more efficient use of health care resources.

    View details for PubMedID 28525586

  • Limited access to special education services for school-aged children with developmental delay RESEARCH IN DEVELOPMENTAL DISABILITIES Twardzik, E., Smit, E., Hatfield, B., Odden, M. C., Dixon-Ibarra, A., MacDonald, M. 2018; 72: 257?64

    Abstract

    Current policy in Oregon limits eligibility of children diagnosed with developmental delay for school-based services. Due to eligibility definitions, children with developmental delay may face additional barriers transitioning from early intervention/early childhood special education into school-based special education services.Examine the relationship between enrollment in school-based special education programs given a change in primary disability diagnosis.Logistic regression models were fit for children who enrolled in early intervention/early childhood special education services with a primary disability diagnosis of developmental delay and changed primary disability diagnosis before third grade (n=5076).Odds of enrollment in future special education were greater in children with a change in primary disability diagnosis after the age of five in comparison to children that had a change in primary disability diagnosis before the age of five, while adjusting for demographic characteristics (adjusted odds ratio: 2.37, 95% CI 1.92, 2.92).Results suggest that children who are diagnosed with a developmental delay and exit early childhood special education due to maximum age of eligibility are more likely to enroll in special education compared to children without a gap in service access.Gaps in service access during early development are associated with the need for supportive services later on in life.

    View details for PubMedID 29227958

  • Patterns of blood pressure response during intensive BP lowering and clinical events: results from the secondary prevention of small subcortical strokes trial BLOOD PRESSURE Ku, E., Scherzer, R., Odden, M. C., Shlipak, M., White, C. L., Field, T. S., Benavente, O., Pergola, P. E., Peralta, C. A. 2018; 27 (2): 73?81

    Abstract

    We applied cluster analysis to identify discrete patterns of concomitant responses of systolic (SBP), diastolic (DBP) and pulse pressure (PP) during intensive BP lowering; and to evaluate their clinical relevance and association with risk of mortality, major vascular events (MVEs), and stroke.We used an unsupervised cluster procedure to identify distinct patterns of BP change during the first 9 months of anti-hypertensive therapy intensification among 1,331 participants in the Secondary Prevention of Small Subcortical Strokes Trial who were previously randomized to lower BP target (SBP?

    View details for PubMedID 28952798

  • Association Between More Intensive vs Less Intensive Blood Pressure Lowering and Risk of Mortality in Chronic Kidney Disease Stages 3 to 5 A Systematic Review and Meta-analysis JAMA INTERNAL MEDICINE Malhotra, R., Hoang Anh Nguyen, Benavente, O., Mete, M., Howard, B. V., Mant, J., Odden, M. C., Peralta, C. A., Cheung, A. K., Nadkarni, G. N., Coleman, R. L., Holman, R. R., Zanchetti, A., Peters, R., Beckett, N., Staessen, J. A., Ix, J. H. 2017; 177 (10): 1498?1505

    Abstract

    Trials in patients with hypertension have demonstrated that intensive blood pressure (BP) lowering reduces the risk of cardiovascular disease and all-cause mortality but may increase the risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown.To conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to investigate if more intensive compared with less intensive BP control is associated with reduced mortality risk in persons with CKD stages 3 to 5.Ovid MEDLINE, Cochrane Library, EMBASE, PubMed, Science Citation Index, Google Scholar, and clinicaltrials.gov electronic databases.All RCTs were included that compared 2 defined BP targets (either active BP treatment vs placebo or no treatment, or intensive vs less intensive BP control) and enrolled adults (?18 years) with CKD stages 3 to 5 (estimated glomerular filtration rate <60 mL/min/1.73 m2) exclusively or that included a CKD subgroup between January 1, 1950, and June 1, 2016.Two of us independently evaluated study quality and extracted characteristics and mortality events among persons with CKD within the intervention phase for each trial. When outcomes within the CKD group had not previously been published, trial investigators were contacted to request data within the CKD subset of their original trials.All-cause mortality during the active treatment phase of each trial.This study identified 30 RCTs that potentially met the inclusion criteria. The CKD subset mortality data were extracted in 18 trials, among which there were 1293 deaths in 15?924 participants with CKD. The mean (SD) baseline systolic BP (SBP) was 148 (16) mm Hg in both the more intensive and less intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the more intensive arm and by 8 mm Hg to 140 mm Hg in the less intensive arm. More intensive vs less intensive BP control resulted in 14.0% lower risk of all-cause mortality (odds ratio, 0.86; 95% CI, 0.76-0.97; P?=?.01), a finding that was without significant heterogeneity and appeared consistent across multiple subgroups.Randomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm.

    View details for PubMedID 28873137

  • A Modified Healthy Aging Index and Its Association with Mortality: The National Health and Nutrition Examination Survey, 1999-2002 JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Wu, C., Smit, E., Sanders, J. L., Newman, A. B., Odden, M. C. 2017; 72 (10): 1437?44

    Abstract

    Comorbidity indices that are based on clinically recognized disease do not capture the full spectrum of health. The Healthy Aging Index (HAI) was recently developed to describe a wider range of health and disease across multiple organ systems. We characterized the distribution of a modified HAI (mHAI) by sociodemographics in a representative sample of the U.S. population. We also examined the association of the mHAI with mortality across individuals with different levels of clinically recognizable comorbidities.Data are from the National Health and Nutrition Examination Survey (1999-2000, 2001-2002) on 2,451 adults aged 60 years or older. Five mHAI components (systolic blood pressure, Digit Symbol Substitution Test, cystatin C, glucose, and respiratory problems) were scored 0 (healthiest), 1, or 2 (unhealthiest) by sex-specific tertiles or clinically relevant cutoffs and summed to construct the mHAI.The mean mHAI score was 4.3; 20.6% had a score of 0-2. 33.2% had a score of 3-4, 31.0% had a score of 5-6, and 15.2% had a score of 7-10. Mean mHAI scores were lower in adults who were younger, non-Hispanic whites, more educated, and married/living with partner. After multivariate adjustment, per unit higher of the mHAI was associated with higher all-cause mortality (HR = 1.19, 95% CI = 1.11-1.27) and higher cardiovascular mortality (HR = 1.23, 95% CI = 1.11-1.35). Within each comorbidity category (0, 1, 2, 3, 4+), the mHAI was still widely distributed and further stratified mortality.Substantial variation exists in the mHAI across sociodemographic subgroups. The mHAI could provide incremental value for mortality risk prediction beyond clinically diagnosed chronic diseases among elders.

    View details for PubMedID 28329253

  • Evaluating the Impact and Cost-Effectiveness of Statin Use Guidelines for Primary Prevention of Coronary Heart Disease and Stroke CIRCULATION Heller, D. J., Coxson, P. G., Penko, J., Pletcher, M. J., Goldman, L., Odden, M. C., Kazi, D. S., Bibbins-Domingo, K. 2017; 136 (12): 1087-+

    Abstract

    Statins are effective in the primary prevention of atherosclerotic cardiovascular disease. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline expands recommended statin use, but its cost-effectiveness has not been compared with other guidelines.We used the Cardiovascular Disease Policy Model to estimate the cost-effectiveness of the ACC/AHA guideline relative to current use, Adult Treatment Panel III guidelines, and universal statin use in all men 45 to 74 years of age and women 55 to 74 years of age over a 10-year horizon from 2016 to 2025. Sensitivity analyses varied costs, risks, and benefits. Main outcomes were incremental cost-effectiveness ratios and numbers needed to treat for 10 years per quality-adjusted life-year gained.Each approach produces substantial benefits and net cost savings relative to the status quo. Full adherence to the Adult Treatment Panel III guideline would result in 8.8 million more statin users than the status quo, at a number needed to treat for 10 years per quality-adjusted life-year gained of 35. The ACC/AHA guideline would potentially result in up to 12.3 million more statin users than the Adult Treatment Panel III guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 68. Moderate-intensity statin use in all men 45 to 74 years of age and women 55 to 74 years of age would result in 28.9 million more statin users than the ACC/AHA guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 108. In all cases, benefits would be greater in men than women. Results vary moderately with different risk thresholds for instituting statins and statin toxicity estimates but depend greatly on the disutility caused by daily medication use (pill burden).At a population level, the ACC/AHA guideline for expanded statin use for primary prevention is projected to treat more people, to save more lives, and to cost less compared with Adult Treatment Panel III in both men and women. Whether individuals benefit from long-term statin use for primary prevention depends more on the disutility associated with pill burden than their degree of cardiovascular risk.

    View details for PubMedID 28687710

  • Functional Status Modifies the Association of Blood Pressure with Death in Elders: Health and Retirement Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Wu, C., Smit, E., Peralta, C. A., Sarathy, H., Odden, M. C. 2017; 65 (7): 1482?89

    Abstract

    To examine whether grip strength, gait speed, and the combination of the two physical functioning measures modified the association of systolic BP (SBP) and diastolic BP (DBP) with mortality.Nationally representative cohort study.Health and Retirement Study.7,492 U.S. adults aged ?65 years.Grip strength was measured by a hand dynamometer and classified as normal (?16 kg for female; ?26 kg for male) and weak. Gait speed was assessed over a 98.5-inch walk and classified as non-slow (?0.60 m/s for female; ?0.52 m/s for male) and slow.Over an average follow-up time of 6.0 years, 1,870 (25.0%) participants died. After adjustment for socio-demographic, behavioral, and clinical measures, elevated SBP (?150 mmHg) and DBP (?90 mmHg) was associated with a 24% (95% CI, 7-43%) and 25% (95% CI, 5-49%) higher mortality among participants with normal grip strength. In contrast, elevated SBP and DBP was associated with a 6% (95% CI, 31 to -27%) and a 16% (95% CI, 46 to -26%) lower mortality among those with weak grip strength (P-values of interactions: both=.07). The inverse relations between BP with death were most pronounced among slow walkers with weak grip strength. The HRs of elevated SBP and DBP for death was 0.85 (95% CI, 0.56-1.29) and 0.53 (95% CI, 0.30-0.96), respectively, and was substantially different from non-slow walkers with normal grip strength (HR = 1.24 and 1.15, respectively; P-values of interactions: both <.001). Therefore, associations of BP with death varied modestly by gait speed.Grip strength modified the association of BP with death. Combination of grip strength and gait speed has incremental value for modifying the association of BP with death.

    View details for PubMedID 28306145

  • Factors Associated With Ischemic Stroke Survival and Recovery in Older Adults STROKE Winovich, D., Longstreth, W. T., Arnold, A. M., Varadhan, R., Al Hazzouri, A., Cushman, M., Newman, A. B., Odden, M. C. 2017; 48 (7): 1818-+

    Abstract

    Little is known about factors that predispose older adults to poor recovery after a stroke. In this study, we sought to evaluate prestroke measures of frailty and related factors as markers of vulnerability to poor outcomes after ischemic stroke.In participants aged 65 to 99 years with incident ischemic strokes from the Cardiovascular Health Study, we evaluated the association of several risk factors (frailty, frailty components, C-reactive protein, interleukin-6, and cystatin C) assessed before stroke with stroke outcomes of survival, cognitive decline (?5 points on Modified Mini-Mental State Examination), and activities of daily living decline (increase in limitations).Among 717 participants with incident ischemic stroke with survival data, slow walking speed, low grip strength, and cystatin C were independently associated with shorter survival. Among participants <80 years of age, frailty and interleukin-6 were also associated with shorter survival. Among 509 participants with recovery data, slow walking speed, and low grip strength were associated with both cognitive and activities of daily living decline poststroke. C-reactive protein and interleukin-6 were associated with poststroke cognitive decline among men only. Frailty status was associated with activities of daily living decline among women only.Markers of physical function-walking speed and grip strength-were consistently associated with survival and recovery after ischemic stroke. Inflammation, kidney function, and frailty also seemed to be determinants of survival and recovery after an ischemic stroke. These markers of vulnerability may identify targets for differing pre and poststroke medical management and rehabilitation among older adults at risk of poor stroke outcomes.

    View details for PubMedID 28526765

  • Association of Blood Pressure Trajectory With Mortality, Incident Cardiovascular Disease, and Heart Failure in the Cardiovascular Health Study AMERICAN JOURNAL OF HYPERTENSION Smitson, C. C., Scherzer, R., Shlipak, M. G., Psaty, B. M., Newman, A. B., Sarnak, M. J., Odden, M. C., Peralta, C. A. 2017; 30 (6): 587?93

    Abstract

    Common blood pressure (BP) trajectories are not well established in elderly persons, and their association with clinical outcomes is uncertain.We used hierarchical cluster analysis to identify discrete BP trajectories among 4,067 participants in the Cardiovascular Health Study using repeated BP measures from years 0 to 7. We then evaluated associations of each BP trajectory cluster with all-cause mortality, incident cardiovascular disease (CVD, defined as stroke or myocardial infarction) (N = 2,837), and incident congestive heart failure (HF) (N = 3,633) using Cox proportional hazard models.Median age was 77 years at year 7. Over a median 9.3 years of follow-up, there were 2,475 deaths, 659 CVD events, and 1,049 HF events. The cluster analysis identified 3 distinct trajectory groups. Participants in cluster 1 (N = 1,838) had increases in both systolic (SBP) and diastolic (DBP) BPs, whereas persons in cluster 2 (N = 1,109) had little change in SBP but declines in DBP. Persons in cluster 3 (N = 1,120) experienced declines in both SBP and DBP. After multivariable adjustment, clusters 2 and 3 were associated with increased mortality risk relative to cluster 1 (hazard ratio = 1.21, 95% confidence interval: 1.06-1.37 and hazard ratio = 1.20, 95% confidence interval: 1.05-1.36, respectively). Compared to cluster 1, cluster 3 had higher rates of incident CVD but associations were not statistically significant in demographic-adjusted models (hazard ratio = 1.16, 95% confidence interval: 0.96-1.39). Findings were similar when stratified by use of antihypertensive therapy.Among community-dwelling elders, distinct BP trajectories were identified by integrating both SBP and DBP. These clusters were found to have differential associations with outcomes.

    View details for PubMedID 28338937

  • Perceived Walking Speed, Measured Tandem Walk, Incident Stroke, and Mortality in Older Latino Adults: A Prospective Cohort Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Al Hazzouri, A., Mayeda, E., Elfassy, T., Lee, A., Odden, M. C., Thekkethala, D., Wright, C. B., Glymour, M. M., Haan, M. N. 2017; 72 (5): 676?82

    Abstract

    Walking speed is associated with functional status and all-cause mortality. Yet the relationship between walking speed and stroke, also a leading cause of disability, remains poorly understood, especially in older Latino adults who suffer from a significant burden of stroke.A total of 1,486 stroke-free participants from the Sacramento Area Latino Study on Aging, aged 60 and older at baseline in 1998-1999, were followed annually through 2010. Participants reported their usual walking speed outdoors which was classified into slow, medium, or fast. We also assessed timed tandem walk ability (unable or eight or more errors vs less than eight errors). We ascertained three incident stroke endpoints: total stroke, nonfatal stroke, and fatal stroke. Using Cox proportional hazards models, we estimated hazard ratios (HRs) for stroke at different walking speed and timed tandem walk categories.Over an average of 6 years of follow-up (SD = 2.8), the incidence rate of total strokes was 23.2/1,000 person-years for slow walkers compared to 15.6/1,000 person-years for medium walkers, and 7.6/1,000 person-years for fast walkers. In Cox models adjusted for sociodemographics, cardiovascular risk, cognition and functional status, and self-rated health, the hazard of total stroke was 31% lower for medium walkers (HR: 0.69, 95% confidence interval [CI]: 0.47, 1.02) and 56% lower for fast walkers (HR: 0.44, 95% CI: 0.24, 0.82) compared with slow walkers. We found similar associations with timed tandem walk ability (fully adjusted HR: 0.66, 95% CI: 0.45, 0.98).Our findings suggest perceived walking speed captures more than self-rated health alone and is a strong risk factor for stroke risk in Latino older adults.

    View details for PubMedID 27549992

  • Effect of Intensive Blood Pressure Control on Gait Speed and Mobility Limitation in Adults 75 Years or Older A Randomized Clinical Trial JAMA INTERNAL MEDICINE Odden, M. C., Peralta, C. A., Berlowitz, D. R., Johnson, K. C., Whittle, J., Kitzman, D. W., Beddhu, S., Nord, J. W., Papademetriou, V., Williamson, J. D., Pajewski, N. M., Systolic Blood Pressure 2017; 177 (4): 500?507

    Abstract

    Intensive blood pressure (BP) control confers a benefit on cardiovascular morbidity and mortality; whether it affects physical function outcomes is unknown.To examine the effect of intensive BP control on changes in gait speed and mobility status.This randomized, clinical trial included 2636 individuals 75 years or older with hypertension and no history of type 2 diabetes or stroke who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Data were collected from November 8, 2010, to December 1, 2015. Analysis was based on intention to treat.Participants were randomized to intensive treatment with a systolic BP target of less than 120 mm Hg (n?=?1317) vs standard treatment with a BP target of less than 140 mm Hg (n?=?1319).Gait speed was measured using a 4-m walk test. Self-reported information concerning mobility was obtained from items on the Veterans RAND 12-Item Health Survey and the EQ-5D. Mobility limitation was defined as a gait speed less than 0.6 meters per second (m/s) or self-reported limitations in walking and climbing stairs.Among the 2629 participants in whom mobility status could be defined (996 women [37.9%]; 1633 men [62.1%]; mean [SD] age, 79.9 [4.0] years), median (interquartile range) follow-up was 3 (2-3) years. No difference in mean gait speed decline was noted between the intensive- and standard-treatment groups (mean difference,?0.0004 m/s per year; 95% CI, -0.005 to 0.005; P?=?.88). No evidence of any treatment group differences in subgroups defined by age, sex, race or ethnicity, baseline systolic BP, chronic kidney disease, or a history of cardiovascular disease were found. A modest interaction was found for the Veterans RAND 12-Item Health Survey Physical Component Summary score, although the effect did not reach statistical significance in either subgroup, with mean differences of 0.004 (95% CI, -0.002 to 0.010) m/s per year among those with scores of at least 40 and -0.008 (95% CI, -0.016 to 0.001) m/s per year among those with scores less than 40 (P?=?.03 for interaction). Multistate models allowing for the competing risk of death demonstrated no effect of intensive treatment on transitions to mobility limitation (hazard ratio, 1.06; 95% CI, 0.92-1.22).Among adults 75 years or older in SPRINT, treating to a systolic BP target of less than 120 mm Hg compared with a target of less than 140 mm Hg had no effect on changes in gait speed and was not associated with changes in mobility limitation.clinicaltrials.gov Identifier: NCT01206062.

    View details for PubMedID 28166324

  • Absolute Rates of Heart Failure, Coronary Heart Disease, and Stroke in Chronic Kidney Disease An Analysis of 3 Community-Based Cohort Studies JAMA CARDIOLOGY Bansal, N., Katz, R., Robinson-Cohen, C., Odden, M. C., Dalrymple, L., Shlipak, M. G., Sarnak, M. J., Siscovick, D. S., Zelnick, L., Psaty, B. M., Kestenbaum, B., Correa, A., Afkarian, M., Young, B., de Boer, I. H. 2017; 2 (3): 314?18

    Abstract

    Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Understanding the relative contributions of cardiovascular disease event types to the excess burden of cardiovascular disease is important for developing effective strategies to improve outcomes.To determine absolute rates and risk differences of incident heart failure (HF), coronary heart disease (CHD), and stroke in participants with vs without CKD.We pooled participants without prevalent cardiovascular disease from 3 community-based cohort studies: the Jackson Heart Study, Cardiovascular Health Study, and Multi-Ethnic Study of Atherosclerosis. The Jackson Heart Study was conducted between 2000 and 2010, the Cardiovascular Health Study was conducted between 1989 and 2003, and the Multi-Ethnic Study of Atherosclerosis was conducted between 2000 and 2012.Chronic kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2, calculated using the combined creatinine-cystatin C CKD-Epidemiology Collaboration Equation.Poisson regression was used to calculate incidence rates (IRs) and risk differences of adjudicated incident HF, CHD, and stroke, comparing participants with vs without CKD.Among 14?462 participants, the mean (SD) age was 63 (12) years, 59% (n?=?8533) were women, and 44% (n?=?6363) were African American. Overall, 1461 (10%) had CKD (mean [SD] estimated glomerular filtration rate, 49 [10] mL/min/1.73 m2). Unadjusted IRs for participants with and without CKD, respectively, were 22.0 (95% CI, 19.3-24.8) and 6.2 (95% CI, 5.8-6.7) per 1000 person-years for HF; 24.5 (95% CI, 21.6-27.5) and 8.4 (95% CI, 7.9-9.0) per 1000 person-years for CHD; and 13.4 (95% CI, 11.3-15.5) and 4.8 (95% CI, 4.4-5.3) for stroke. Adjusting for demographics, cohort, hypertension, diabetes, hyperlipidemia, and tobacco use, risk differences comparing participants with vs without CKD (per 1000 person-years) were 2.3 (95% CI, 1.2-3.3) for HF, 2.3 (95% CI, 1.2-3.4) for CHD, and 0.8 (95% CI, 0.09-1.5) for stroke. Among African American and Hispanic participants, adjusted risk differences comparing participants with vs without CKD for HF were 3.5 (95% CI, 1.5-5.5) and 7.8 (95% CI, 2.2-13.3) per 1000 person-years, respectively.Among 3 diverse community-based cohorts, CKD was associated with an increased risk of HF that was similar in magnitude to CHD and greater than stroke. The excess risk of HF associated with CKD was particularly large among African American and Hispanic individuals. Efforts to improve health outcomes for patients with CKD should prioritize HF in addition to CHD prevention.

    View details for PubMedID 28002548

  • Visit-to-Visit Blood Pressure Variability and Mortality and Cardiovascular Outcomes Among Older Adults: The Health, Aging, and Body Composition Study AMERICAN JOURNAL OF HYPERTENSION Wu, C., Shlipak, M. G., Stawski, R. S., Peralta, C. A., Psaty, B. M., Harris, T. B., Satterfield, S., Shiroma, E. J., Newman, A. B., Odden, M. C., Hlth ABC Study 2017; 30 (2): 151?58

    Abstract

    Level of blood pressure (BP) is strongly associated with cardiovascular (CV) events and mortality. However, it is questionable whether mean BP can fully capture BP-related vascular risk. Increasing attention has been given to the value of visit-to-visit BP variability.We examined the association of visit-to-visit BP variability with mortality, incident myocardial infarction (MI), and incident stroke among 1,877 well-functioning elders in the Health, Aging, and Body Composition Study. We defined visit-to-visit diastolic BP (DBP) and systolic BP (SBP) variability as the root-mean-square error of person-specific linear regression of BP as a function of time. Alternatively, we counted the number of considerable BP increases and decreases (separately; 10mm Hg for DBP and 20mm Hg for SBP) between consecutive visits for each individual.Over an average follow-up of 8.5 years, 623 deaths (207 from CV disease), 153 MIs, and 156 strokes occurred. The median visit-to-visit DBP and SBP variability was 4.96 mmHg and 8.53 mmHg, respectively. After multivariable adjustment, visit-to-visit DBP variability was related to higher all-cause (hazard ratio (HR) = 1.18 per 1 SD, 95% confidence interval (CI) = 1.01-1.37) and CV mortality (HR = 1.35, 95% CI = 1.05-1.73). Additionally, individuals having more considerable decreases of DBP (?10mm Hg between 2 consecutive visits) had higher risk of all-cause (HR = 1.13, 95% CI = 0.99-1.28) and CV mortality (HR = 1.30, 95% CI = 1.05-1.61); considerable increases of SBP (?20mm Hg) were associated with higher risk of all-cause (HR = 1.18, 95% CI = 1.03-1.36) and CV mortality (HR = 1.37, 95% CI = 1.08-1.74).Visit-to-visit DBP variability and considerable changes in DBP and SBP were risk factors for mortality in the elderly.

    View details for PubMedID 27600581

  • Blood Pressure Trajectory, Gait Speed, and Outcomes: The Health, Aging, and Body Composition Study (vol 71, pg 1688, 2016) JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Odden, M. C., Wu, C., Shlipak, M. G., Psaty, B. M., Katz, R., Applegate, W. B., Harris, T., Newman, A. B., Peralta, C. A., Hlth ABC Study 2016; 71 (12): E1

    View details for PubMedID 27838648

  • Blood Pressure Trajectory, Gait Speed, and Outcomes: The Health, Aging, and Body Composition Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Odden, M. C., Wu, C., Shlipak, M. G., Psaty, B. M., Katz, R., Applegate, W. B., Harris, T., Newman, A. B., Peralta, C. A., Hlth ABC Study 2016; 71 (12): 1688?94

    Abstract

    The present study aimed to (i) evaluate previous observations that the association of blood pressure (BP) with outcomes varies by gait speed and (ii) evaluate the association of subsequent changes in BP and cardiovascular risk.Participants included 2,669 adults aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) study. Gait speed was dichotomized at ?1.0 m/s over a 20-m test at baseline. BP was measured at baseline, and changes in BP over 5 years were evaluated using (i) population-based trajectory models and (ii) intraindividual mean and slope.Over a mean of 10 years, there were 1,366 deaths, 336 first myocardial infarctions, and 295 first strokes. There was a differential pattern of association between baseline systolic BP and diastolic BP and outcomes among brisk and moderate speed walkers. For example, the association between higher diastolic BP and mortality was in the protective direction for moderate speed walkers (hazard ratio = 0.75; 95% confidence interval: 0.63, 0.91) per 10 mmHg higher, whereas it was null in brisk walkers (hazard ratio = 1.05; 95% confidence interval: 0.98, 1.11), p value for interaction .01. The 5-year population-based trajectories did not add important information beyond baseline BP. Individual slopes in both systolic BP and diastolic BP did not appear to have important associations with the outcomes.In this study, we found that the overall level of BP was associated with myocardial infarction, stroke, and death, and this association differed by baseline gait speed, whereas changes in BP were not associated with these outcomes.

    View details for PubMedID 27142696

  • Effectiveness of a Scaled-Up Arthritis Self-Management Program in Oregon: Walk With Ease AMERICAN JOURNAL OF PUBLIC HEALTH Conte, K. P., Odden, M. C., Linton, N. M., Harvey, S. 2016; 106 (12): 2227?30

    Abstract

    To evaluate the effectiveness of Walk With Ease (WWE), an evidence-based arthritis self-management program that was scaled up in Oregon in 2012 to 2014.Guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework, we collected participant surveys and attendance records and conducted observations. Preprogram and postprogram, participants self-reported pain and fatigue (scale: 0-10 points; high scores indicate more pain and fatigue) and estimated episodes of physical activity per week in the last month.Recruitment successfully reached the targeted population-sedentary adults with arthritis (n?=?598). Participants reported significant reduction in pain (-0.47 points; P?=?.006) and fatigue (-0.58 points; P?=?.021) and increased physical activity (0.86 days/week; P?

    View details for PubMedID 27736216

  • Projected Impact of Mexico's Sugar-Sweetened Beverage Tax Policy on Diabetes and Cardiovascular Disease: A Modeling Study PLOS MEDICINE Maria Sanchez-Romero, L., Penko, J., Coxson, P. G., Fernandez, A., Mason, A., Moran, A. E., Avila-Burgos, L., Odden, M., Barquera, S., Bibbins-Domingo, K. 2016; 13 (11): e1002158

    Abstract

    Rates of diabetes in Mexico are among the highest worldwide. In 2014, Mexico instituted a nationwide tax on sugar-sweetened beverages (SSBs) in order to reduce the high level of SSB consumption, a preventable cause of diabetes and cardiovascular disease (CVD). We used an established computer simulation model of CVD and country-specific data on demographics, epidemiology, SSB consumption, and short-term changes in consumption following the SSB tax in order to project potential long-range health and economic impacts of SSB taxation in Mexico.We used the Cardiovascular Disease Policy Model-Mexico, a state transition model of Mexican adults aged 35-94 y, to project the potential future effects of reduced SSB intake on diabetes incidence, CVD events, direct diabetes healthcare costs, and mortality over 10 y. Model inputs included short-term changes in SSB consumption in response to taxation (price elasticity) and data from government and market research surveys and public healthcare institutions. Two main scenarios were modeled: a 10% reduction in SSB consumption (corresponding to the reduction observed after tax implementation) and a 20% reduction in SSB consumption (possible with increases in taxation levels and/or additional measures to curb consumption). Given uncertainty about the degree to which Mexicans will replace calories from SSBs with calories from other sources, we evaluated a range of values for calorie compensation. We projected that a 10% reduction in SSB consumption with 39% calorie compensation among Mexican adults would result in about 189,300 (95% uncertainty interval [UI] 155,400-218,100) fewer incident type 2 diabetes cases, 20,400 fewer incident strokes and myocardial infarctions, and 18,900 fewer deaths occurring from 2013 to 2022. This scenario predicts that the SSB tax could save Mexico 983 million international dollars (95% UI $769 million-$1,173 million). The largest relative and absolute reductions in diabetes and CVD events occurred in the youngest age group modeled (35-44 y). This study's strengths include the use of an established mathematical model of CVD and use of contemporary Mexican vital statistics, data from health surveys, healthcare costs, and SSB price elasticity estimates as well as probabilistic and deterministic sensitivity analyses to account for uncertainty. The limitations of the study include reliance on US-based studies for certain inputs where Mexico-specific data were lacking (specifically the associations between risk factors and CVD outcomes [from the Framingham Heart Study] and SSB calorie compensation assumptions), limited data on healthcare costs other than those related to diabetes, and lack of information on long-term SSB price elasticity that is specific to geographic and economic subgroups.Mexico's high diabetes prevalence represents a public health crisis. While the long-term impact of Mexico's SSB tax is not yet known, these projections, based on observed consumption reductions, suggest that Mexico's SSB tax may substantially decrease morbidity and mortality from diabetes and CVD while reducing healthcare costs.

    View details for PubMedID 27802278

  • Association of retirement age with mortality: a population-based longitudinal study among older adults in the USA JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH Wu, C., Odden, M. C., Fisher, G. G., Stawski, R. S. 2016; 70 (9): 917?23

    Abstract

    Retirement is an important transitional process in later life. Despite a large body of research examining the impacts of health on retirement, questions still remain regarding the association of retirement age with survival. We aimed to examine the association between retirement age and mortality among healthy and unhealthy retirees and to investigate whether sociodemographic factors modified this association.On the basis of the Health and Retirement Study, 2956 participants who were working at baseline (1992) and completely retired during the follow-up period from 1992 to 2010 were included. Healthy retirees (n=1934) were defined as individuals who self-reported health was not an important reason to retire. The association of retirement age with all-cause mortality was analysed using the Cox model. Sociodemographic effect modifiers of the relation were examined.Over the study period, 234 healthy and 262 unhealthy retirees died. Among healthy retirees, a 1-year older age at retirement was associated with an 11% lower risk of all-cause mortality (95% CI 8% to 15%), independent of a wide range of sociodemographic, lifestyle and health confounders. Similarly, unhealthy retirees (n=1022) had a lower all-cause mortality risk when retiring later (HR 0.91, 95% CI 0.88 to 0.94). None of the sociodemographic factors were found to modify the association of retirement age with all-cause mortality.Early retirement may be a risk factor for mortality and prolonged working life may provide survival benefits among US adults.

    View details for PubMedID 27001669

  • Gender Differences in the Combined Effects of Cardiovascular Disease and Osteoarthritis on Progression to Functional Impairment in Older Mexican Americans JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Haan, M. N., Lee, A., Odden, M. C., Aiello, A. E., To, T., Neuhaus, J. M. 2016; 71 (8): 1089?95

    Abstract

    Comorbidity (COM) is an important issue in aging. Cardiovascular disease (CVD) and osteoarthritis separately and together may modify the trajectories of functional decline. This analysis examines whether specific and unrelated COMs influence functional change differently and vary by gender.A cohort study of 1,789 (aged 60 years and older) Mexican Americans was followed annually for up to 10 years. We created four groups of COM (CVD alone, lower body osteoarthritis alone [OA], neither, or both). We employed mixed effects Poisson models with Instrumental Activities of Daily Living (IADL) as the outcome. We tested whether the association between COM and decline in functional status differed by gender.IADL impairments in those with CVD, OA, or both were significantly higher at baseline and increased more rapidly over time compared to those with neither condition. Compared to women with no COM, the number of IADL impairments in women with CVD alone were 1.36 times greater, with OA were 1.35 times greater, and both conditions were 1.26 times greater. Compared to men with no COM, IADL impairments in men with CVD alone were 1.15 times greater, OA alone were 1.12 times greater, and both were 1.26 times greater.Over time, the influence of COM on functional decline differs by specific combinations of COM and by gender. Aggregate COM scales obscure the biological and temporal heterogeneity in the effects of COM. Time-dependent-specific COMs better assess the development of impairment. Women experience a higher burden of functional impairment due to COM than men.

    View details for PubMedID 26893469

  • Trajectories of function and biomarkers with age: the CHS All Stars Study INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Newman, A. B., Sanders, J. L., Kizer, J. R., Boudreau, R. M., Odden, M. C., Al Hazzouri, A., Arnold, A. M. 2016; 45 (4): 1135?45

    Abstract

    Multimorbidity is a major driver of physical and cognitive impairment, but rates of decline are also related to ageing. We sought to determine trajectories of decline in a large cohort by disease status, and examined their correspondence with biomarkers of ageing processes including growth hormone, sex steroid, inflammation, visceral adiposity and kidney function pathways.We have followed the 5888 participants in the Cardiovascular Health Study (CHS) for healthy ageing and longevity since 1989-90. Gait speed, grip strength, modified mini-mental status examination (3MSE) and the digit symbol substitution test (DSST) were assessed annually to 1998-99 and again in 2005-06. Insulin-like growth hormone (IGF-1), dehydroepiandrosterone sulphate (DHEAS), interleukin-6 (IL-6), adiponectin and cystatin-C were assessed 3-5 times from stored samples. Health status was updated annually and dichotomized as healthy vs not healthy. Trajectories for each function measure and biomarker were estimated using generalized estimating equations as a function of age and health status using standardized values.Trajectories of functional decline showed strong age acceleration late in life in healthy older men and women as well as in chronically ill older adults. Adiponectin, IL-6 and cystatin-C tracked with functional decline in all domains; cystatin-C was consistently associated with functional declines independent of other biomarkers. DHEAS was independently associated with grip strength and IL-6 with grip strength and gait speed trajectories.Functional decline in late life appears to mark a fundamental ageing process in that it occurred and was accelerated in late life regardless of health status. Cystatin C was most consistently associated with these functional declines.

    View details for PubMedID 27272182

  • Response by Peralta et al to Letter Regarding Article, "Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke: A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial" CIRCULATION Peralta, C. A., McClure, L. A., Scherzer, R., Odden, M. C., White, C. L., Shlipak, M., Benavente, O., Pergola, P. E. 2016; 134 (4): E26?E27

    View details for PubMedID 27462061

  • Responses to Financial Loss During the Great Recession: An Examination of Sense of Control in Late Midlife JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Mejia, S. T., Settersten, R. A., Odden, M. C., Hooker, K. 2016; 71 (4): 734?44

    Abstract

    The "Great Recession" shocked the primary institutions that help individuals and families meet their needs and plan for the future. This study examines middle-aged adults' experiences of financial loss and considers how socioeconomic and interpersonal resources facilitate or hinder maintaining a sense of control in the face of economic uncertainty.Using the 2006 and 2010 waves of the Health and Retirement Study, change in income and wealth, giving help to and receiving help from others, household complexity, and sense of control were measured among middle-aged adults (n = 3,850; age = 51-60 years).Socioeconomic resources predicted both the level of and change in the engagement of interpersonal resources prior to and during the Great Recession. Experiences of financial loss were associated with increased engagement of interpersonal resources and decreased sense of control. The effect of financial loss was dampened by education. Sense of control increased with giving help and decreased with household complexity.Findings suggest that, across socioeconomic strata, proportional loss in financial resources resulted in a loss in sense of control. However, responses to financial loss differed by socioeconomic status, which differentiated the ability to maintain a sense of control following financial loss.

    View details for PubMedID 26307482

  • Functional Status and Antihypertensive Therapy in Older Adults: A New Perspective on Old Data AMERICAN JOURNAL OF HYPERTENSION Charlesworth, C. J., Peralta, C. A., Odden, M. C. 2016; 29 (6): 690?95

    Abstract

    Functional status may be useful for identifying older adults who benefit from lower blood pressure. We examined whether functional status modifies the effect of antihypertensive treatment among older adults.Post hoc analyses of the Systolic Hypertension in the Elderly Program (SHEP), a randomized trial of antihypertensive therapy vs. placebo (1985-1991) in 4,736 adults aged 60 years or older with isolated systolic hypertension. Outcomes were all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, falls, and symptoms of hypotension. The effect modifier of interest was functional status, assessed by self-reported physical ability limitation (PAL).Among persons with no PAL, those receiving treatment had a lower rate of death, CV death, and MI compared with placebo (4.0, 2.9, and 4.2 per 1,000 person-years lower, respectively). In contrast, among persons with a PAL, those receiving treatment had a higher rate of death, CV death, and MI compared with placebo (8.6, 5.3, and 2.7 per 1,000 person-years higher, respectively). These patterns persisted in Cox models, although interaction terms did not reach statistical significance. Treatment remained protective for stroke regardless of functional status. The rate of falls associated with treatment differed by functional status; incidence-rate ratio = 0.81, 95% confidence interval (CI) = (0.66, 0.99), and 1.32, 95% CI = (0.87, 2.00) in participants without and with a PAL, respectively, in models adjusted for demographics and baseline blood pressure (P-value for interaction, 0.04).Functional status may modify the effect of antihypertensive treatment on MI, mortality, and falls, but not stroke, in older adults. Functional status should be examined in other trial settings.

    View details for PubMedID 26541570

  • Gait Speed as a Guide for Blood Pressure Targets in Older Adults: A Modeling Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Odden, M. C., Moran, A. E., Coxson, P. G., Peralta, C. A., Goldman, L., Bibbins-Domingo, K. 2016; 64 (5): 1015?23

    Abstract

    To evaluate the potential for gait speed to inform decisions regarding optimal systolic blood pressure targets in older adults.Forecasting study from 2014 to 2023 using the Cardiovascular Disease Policy Model, a Markov model.National Health and Nutrition Examination Survey.U.S. adults aged 60-94 stratified into fast walking, slow walking, and poor functioning (noncompleters) based on measured gait speed.Lowering SBP to a target of 140 or 150 mmHg was modeled in persons with (secondary prevention) and without (primary prevention) a history of coronary heart disease or stroke. Based on clinical trials and observational studies, it was projected that slow-walking and poor-functioning participants would have greater noncardiovascular mortality. Myocardial infarctions (MIs), strokes, deaths, cost, and disability-adjusted life years (DALYs) were measured.Regardless of gait speed, it was projected that secondary prevention to a systolic blood pressure (SBP) of 140 mmHg would prevent more events and save more money than secondary prevention to 150 mmHg. Similarly, primary prevention to 140 mmHg in fast-walking adults was projected to prevent events and save money. In slow-walking adults, primary prevention to 150 mmHg was projected to prevent MIs and strokes and save DALYs but was cost saving only in men; intensification to 140 mmHg is of uncertain benefit in slow-walking individuals. Primary prevention in poor-functioning adults to a target of 140 or 150 mmHg SBP is projected to decrease DALYs.The most cost-effective SBP target varies according to history of cardiovascular disease and gait speed in persons aged 60-94. These projections highlight the need for better estimates of the benefits and harms of antihypertensive medications in a diverse group of older adults, because the net benefit is sensitive to the characteristics of the population treated.

    View details for PubMedID 27225357

  • Incident Atrial Fibrillation and Disability-Free Survival in the Cardiovascular Health Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Wallace, E. R., Siscovick, D. S., Sitlani, C. M., Dublin, S., Mitchell, P. H., Odden, M. C., Hirsch, C. H., Thielke, S., Heckbert, S. R. 2016; 64 (4): 838?43

    Abstract

    To assess the associations between incident atrial fibrillation (AF) and disability-free survival and risk of disability.Prospective cohort study.Cardiovascular Health Study.Individuals aged 65 and older and enrolled in fee-for-service Medicare followed between 1991 and 2009 (MN = 4,046). Individuals with prevalent AF, activity of daily living (ADL) disability, or a history of stroke or heart failure at baseline were excluded.Incident AF was identified according to annual study electrocardiogram, hospital discharge diagnosis, or Medicare claims. Disability-free survival was defined as survival free of ADL disability (any difficulty or inability in bathing, dressing, eating, using the toilet, walking around the home, or getting out of a bed or chair). ADLs were assessed at annual study visits or in a telephone interview. Association between incident AF and disability-free survival or risk of disability was estimated using Cox proportional hazards models.Over an average of 7.0 years of follow-up, 660 individuals (16.3%) developed incident AF, and 3,112 (77%) became disabled or died. Incident AF was associated with shorter disability-free survival (hazard ratio (HR) for death or ADL disability = 1.71, 95% confidence interval (CI) = 1.55-1.90) and a higher risk of ADL disability (HR = 1.36, 95% CI = 1.18-1.58) than in individuals with no history of AF. This association persisted after adjustment for interim stroke and heart failure.These results suggest that AF is a risk factor for shorter functional longevity in older adults, independent of other risk factors and comorbid conditions.

    View details for PubMedID 26926559

  • Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial CIRCULATION Peralta, C. A., McClure, L. A., Scherzer, R., Odden, M. C., White, C. L., Shlipak, M., Benavente, O., Pergola, P. 2016; 133 (6): 584?91

    Abstract

    The effect of intensive blood pressure (BP) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established.Among 2610 participants randomized to a lower (<130 mm Hg) versus higher (130-149 mm Hg) systolic BP target with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events, and the composite of stroke, death, major vascular events, or myocardial infarction using multivariable Cox regression, separately and jointly including a test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11 years; 949 participants (36%) were diabetic; and mean eGFR was 80±19 mL·min(-1)·1.73 m(-2). At 9 months, achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group, and differences were maintained throughout follow-up (mean, 3.2 years). Compared with the higher target, the lower BP target had a -0.50-mL·min(-1)·1.73 m(-2) per year (95% confidence interval [CI], -0.79 to -0.21) faster eGFR decline. Differences were most pronounced during the first year (-2.1 mL·min(-1)·1.73 m(-2); 95% CI, -0.97 to -3.2), whereas rates of eGFR decline did not differ after year 1 (-0.095; 95% CI, -0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1-1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1-1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73-1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15-3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50-1.75; all P for interaction <0.06).In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering.URL: http://www.clinicalTrials.gov. Unique identifier: NCT00059306.

    View details for PubMedID 26762524

  • Achieved Blood Pressure and Outcomes in the Secondary Prevention of Small Subcortical Strokes Trial HYPERTENSION Odden, M. C., McClure, L. A., Sawaya, B., White, C. L., Peralta, C. A., Field, T. S., Hart, R. G., Benavente, O. R., Pergola, P. E. 2016; 67 (1): 63?69

    Abstract

    Studies suggest a J-shaped association between blood pressure and cardiovascular events in the setting of intensive systolic blood pressure control; whether there is a similar association with stroke remains less well established. The Secondary Prevention of Small Subcortical Strokes was a randomized trial to evaluate higher (130-149 mm Hg) versus lower (<130 mm Hg) systolic blood pressure targets in participants with recent lacunar infarcts. We evaluated the association of mean achieved blood pressure, 6 months after randomization, and recurrent stroke, major vascular events, and all-cause mortality. After a mean follow up of 3.7 years, there was a J-shaped association between achieved blood pressure and outcomes; the lowest risk was at ?124 and 67 mm Hg systolic and diastolic blood pressure, respectively. For example, above a systolic blood pressure of 124 mm Hg, 1 standard deviation higher (11.1 mm Hg) was associated with increased mortality (adjusted hazard ratio: 1.9; 95% confidence interval: 1.4, 2.7), whereas below this level, this relationship was inverted (0.29; 0.10, 0.79), P<0.001 for interaction. Above a diastolic blood pressure of 67 mm Hg, a 1 standard deviation higher (8.2 mm Hg) was associated with an increased risk of stroke (2.2; 1.4, 3.6), whereas below this level, the association was in the opposite direction (0.34; 0.13, 0.89), P=0.02 for interaction. The lowest risk of all events occurred at a nadir of ?120 to 128 mm Hg systolic blood pressure and 65 to 70 mm Hg diastolic blood pressure. Future studies should evaluate the impact of excessive blood pressure reduction, especially in older populations with preexisting vascular disease.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

    View details for PubMedID 26553236

  • Microvascular and Macrovascular Abnormalities and Cognitive and Physical Function in Older Adults: Cardiovascular Health Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Kim, D., Grodstein, F., Newman, A. B., Chaves, P. M., Odden, M. C., Klein, R., Sarnak, M. J., Lipsitz, L. A. 2015; 63 (9): 1886?93

    Abstract

    To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical functionCross-sectional analysis of the Cardiovascular Health Study (1998-1999).Community.Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5).Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test (TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand)Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = -0.30, 95% confidence interval (CI) = -0.37 to -0.24) and physical (mean score difference = -0.32, 95% CI = -0.38 to -0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: -0.16, 95% CI = -0.24 to -0.08 vs -0.13, 95% CI = -0.20 to -0.06; physical function: -0.15, 95% CI = -0.22 to -0.08 vs -0.12, 95% CI = -0.18 to -0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function.Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication.

    View details for PubMedID 26338279

  • Polypharmacy Among Adults Aged 65 Years and Older in the United States: 1988-2010 JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Charlesworth, C. J., Smit, E., Lee, D. H., Alramadhan, F., Odden, M. C. 2015; 70 (8): 989?95

    Abstract

    Older adults frequently have several chronic health conditions which require multiple medications. We illustrated trends in prescription medication use over 20 years in the United States, and described characteristics of older adults using multiple medications in 2009-2010.Participants included 13,869 adults aged 65 years and older in the National Health & Nutrition Examination Survey (1988-2010). Prescription medication use was verified by medication containers. Potentially inappropriate medications were defined by the 2003 Beers Criteria.Between 1988 and 2010 the median number of prescription medications used among adults aged 65 and older doubled from 2 to 4, and the proportion taking ?5 medications tripled from 12.8% (95% confidence interval: 11.1, 14.8) to 39.0% (35.8, 42.3).These increases were driven, in part, by rising use of cardioprotective and antidepressant medications. Use of potentially inappropriate medications decreased from 28.2% (25.5, 31.0) to 15.1% (13.2, 17.3) between 1988 and 2010. Higher medication use was associated with higher prevalence of functional limitation, activities of daily living limitation, and confusion/memory problems in 2009-2010, although these associations did not remain after adjustment for covariates. In multivariable models, older age, number of chronic conditions, and annual health care visits were associated with increased odds of using both 1-4 and ?5 medications. Additionally, body mass index, higher income-poverty ratio, former smoking, and non-black non-white race were associated with use of ?5 medications.Prescription medication use increased dramatically among older adults between 1988 and 2010. Contemporary older adults on multiple medications have worse health status compared with those on less medications, and appear to be a vulnerable population.

    View details for PubMedID 25733718

  • Blood Pressure in Older Adults: the Importance of Frailty CURRENT HYPERTENSION REPORTS Odden, M. C., Beilby, P. R., Peralta, C. A. 2015; 17 (7): 55

    Abstract

    The importance of high blood pressure (BP) and the effect of BP lowering in older adults remain controversial due to the mixed evidence in this population. Frailty status may resolve the apparently conflicting findings and identify subpopulations who share common risk. Emerging evidence demonstrates that low BP is associated with poor outcomes in older frail adults or those with poor functional status. In contrast, in non-frail older adults, low BP appears beneficial. Frail older adults may be at increased risk of hypotension, serious fall injuries, and polypharmacy. Additionally, peripheral BP may not be the best prognostic measure in this population. The majority of clinical practice guidelines give little recommendation for frail older adults, which is likely due to their systematic underrepresentation in randomized controlled trials. Future studies need to consider modifications to safely include frail older adults, and guidelines should consider inclusion of evidence beyond randomized controlled trials.

    View details for PubMedID 26068656

  • Cost-Effectiveness of Hypertension Therapy According to 2014 Guidelines NEW ENGLAND JOURNAL OF MEDICINE Moran, A. E., Odden, M. C., Thanataveerat, A., Tzong, K. Y., Rasmussen, P. W., Guzman, D., Williams, L., Bibbins-Domingo, K., Coxson, P. G., Goldman, L. 2015; 372 (17): 1677

    View details for Web of Science ID 000353294000028

    View details for PubMedID 25901443

  • Cost-Effectiveness and Population Impact of Statins for Primary Prevention in Adults Aged 75 Years or Older in the United States ANNALS OF INTERNAL MEDICINE Odden, M. C., Pletcher, M. J., Coxson, P. G., Thekkethala, D., Guzman, D., Heller, D., Goldman, L., Bibbins-Domingo, K. 2015; 162 (8): 533-+

    Abstract

    Evidence to guide primary prevention in adults aged 75 years or older is limited.To project the population impact and cost-effectiveness of statin therapy in adults aged 75 years or older.Forecasting study using the Cardiovascular Disease Policy Model, a Markov model.Trial, cohort, and nationally representative data sources.U.S. adults aged 75 to 94 years.10 years.Health care system.Statins for primary prevention based on low-density lipoprotein cholesterol threshold of 4.91 mmol/L (190 mg/dL), 4.14 mmol/L (160 mg/dL), or 3.36 mmol/L (130 mg/dL); presence of diabetes; or 10-year risk score of at least 7.5%.Myocardial infarction (MI), coronary heart disease (CHD) death, disability-adjusted life-years, and costs.All adults aged 75 years or older in the National Health and Nutrition Examination Survey have a 10-year risk score greater than 7.5%. If statins had no effect on functional limitation or cognitive impairment, all primary prevention strategies would prevent MIs and CHD deaths and be cost-effective. Treatment of all adults aged 75 to 94 years would result in 8 million additional users and prevent 105 000 (4.3%) incident MIs and 68 000 (2.3%) CHD deaths at an incremental cost per disability-adjusted life-year of $25 200.An increased relative risk for functional limitation or mild cognitive impairment of 1.10 to 1.29 could offset the cardiovascular benefits.Limited trial evidence targeting primary prevention in adults aged 75 years or older.At effectiveness similar to that in trials, statins are projected to be cost-effective for primary prevention; however, even a small increase in geriatric-specific adverse effects could offset the cardiovascular benefit. Improved data on the potential benefits and harms of statins are needed to inform decision making.American Heart Association Western States Affiliate, National Institute on Aging, and the National Institute for Diabetes on Digestive and Kidney Diseases.

    View details for DOI 10.7326/M14-1430

    View details for Web of Science ID 000353244300013

    View details for PubMedID 25894023

    View details for PubMedCentralID PMC4476404

  • Years of Able Life in Older Persons-The Role of Cardiovascular Imaging and Biomarkers: The Cardiovascular Health Study JOURNAL OF THE AMERICAN HEART ASSOCIATION Alshawabkeh, L. I., Yee, L. M., Gardin, J. M., Gottdiener, J. S., Odden, M. C., Bartz, T. M., Arnold, A. M., Mukamal, K. J., Wallace, R. B. 2015; 4 (4)

    Abstract

    As the U.S. population grows older, there is greater need to examine physical independence. Previous studies have assessed risk factors in relation to either disability or mortality, but an outcome that combines both is still needed.The Cardiovascular Health Study is a population-based, prospective study where participants underwent baseline echocardiogram, measurement of carotid intima-media thickness (IMT), and various biomarkers, then followed for up to 18 years. Years of able life (YAL) constituted the number of years the participant was able to perform all activities of daily living. Linear regression was used to model the relationship between selected measures and outcomes, adjusted for confounding variables. Among 4902 participants, mean age was 72.6 ± 5.4 years, median YAL for males was 8.8 (interquartile range [IQR], 4.3 to 13.8) and 10.3 (IQR, 5.8 to 15.8) for females. Reductions in YAL in the fully adjusted model for females and males, respectively, were: -1.34 (95% confidence interval [CI], -2.18, -0.49) and -1.41 (95% CI, -2.03, -0.8) for abnormal left ventricular (LV) ejection fraction, -0.5 (95% CI, -0.78, -0.22) and -0.62 (95% CI, -0.87, -0.36) per SD increase in LV mass, -0.5 (95% CI, -0.7, -0.29) and -0.79 (95% CI, -0.99, -0.58) for IMT, -0.5 (95% CI, -0.64, -0.37) and -0.79 (95% CI, -0.94, -0.65) for N-terminal pro-brain natriuretic peptide, -1.08 (95% CI, -1.34, -0.83) and -0.73 (95% CI, -0.97, -0.5) for high-sensitivity troponin-T, and -0.26 (95% CI, -0.42, -0.09) and -0.23 (95% CI, -0.41, -0.05) for procollagen-III N-terminal propeptide. Most tested variables remained significant even after adjusting for incident cardiovascular (CV) disease.In this population-based cohort, variables obtained by CV imaging and biomarkers of inflammation, coagulation, atherosclerosis, myocardial injury and stress, and cardiac collagen turnover were associated with YAL, an important outcome that integrates physical ability and longevity in older persons.

    View details for PubMedID 25907126

  • Cost-Effectiveness of Hypertension Therapy According to 2014 Guidelines NEW ENGLAND JOURNAL OF MEDICINE Moran, A. E., Odden, M. C., Thanataveerat, A., Tzong, K. Y., Rasmussen, P. W., Guzman, D., Williams, L., Bibbins-Domingo, K., Coxson, P. G., Goldman, L. 2015; 372 (5): 447?55

    Abstract

    On the basis of the 2014 guidelines for hypertension therapy in the United States, many eligible adults remain untreated. We projected the cost-effectiveness of treating hypertension in U.S. adults according to the 2014 guidelines.We used the Cardiovascular Disease Policy Model to simulate drug-treatment and monitoring costs, costs averted for the treatment of cardiovascular disease, and quality-adjusted life-years (QALYs) gained by treating previously untreated adults between the ages of 35 and 74 years from 2014 through 2024. We assessed cost-effectiveness according to age, hypertension level, and the presence or absence of chronic kidney disease or diabetes.The full implementation of the new hypertension guidelines would result in approximately 56,000 fewer cardiovascular events and 13,000 fewer deaths from cardiovascular causes annually, which would result in overall cost savings. The projections showed that the treatment of patients with existing cardiovascular disease or stage 2 hypertension would save lives and costs for men between the ages of 35 and 74 years and for women between the ages of 45 and 74 years. The treatment of men or women with existing cardiovascular disease or men with stage 2 hypertension but without cardiovascular disease would remain cost-saving even if strategies to increase medication adherence doubled treatment costs. The treatment of stage 1 hypertension was cost-effective (defined as <$50,000 per QALY) for all men and for women between the ages of 45 and 74 years, whereas treating women between the ages of 35 and 44 years with stage 1 hypertension but without cardiovascular disease had intermediate or low cost-effectiveness.The implementation of the 2014 hypertension guidelines for U.S. adults between the ages of 35 and 74 years could potentially prevent about 56,000 cardiovascular events and 13,000 deaths annually, while saving costs. Controlling hypertension in all patients with cardiovascular disease or stage 2 hypertension could be effective and cost-saving. (Funded by the National Heart, Lung, and Blood Institute and others.).

    View details for PubMedID 25629742

  • Prognostic Implications of Microvascular and Macrovascular Abnormalities in Older Adults: Cardiovascular Health Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Kim, D., Grodstein, F., Newman, A. B., Chaves, P. M., Odden, M. C., Klein, R., Sarnak, M. J., Patel, K. V., Lipsitz, L. A. 2014; 69 (12): 1495?1502

    Abstract

    Microvascular and macrovascular abnormalities are frequently found on noninvasive tests performed in older adults. Their prognostic implications on disability and life expectancy have not been collectively assessed.This prospective study included 2,452 adults (mean age: 79.5 years) with available measures of microvascular (brain, retina, kidney) and macrovascular abnormalities (brain, carotid, coronary, peripheral artery) in the Cardiovascular Health Study. The burden of microvascular and macrovascular abnormalities was examined in relation to total, activity-of-daily-living disability-free, and severe disability-free life expectancies in the next 10 years (1999-2009).At 75 years, individuals with low burden of both abnormalities lived, on average, 8.71 years (95% confidence interval: 8.29, 9.12) of which 7.67 years (7.16, 8.17) were without disability. In comparison, individuals with high burden of both abnormalities had shortest total life expectancy (6.95 years [6.52, 7.37]; p < .001) and disability-free life expectancy (5.60 years [5.10, 6.11]; p < .001). Although total life expectancy was similarly reduced for those with high burden of either type of abnormalities (microvascular: 7.96 years [7.50, 8.42] vs macrovascular: 8.25 years [7.80, 8.70]; p = .10), microvascular abnormalities seemed to have larger impact than macrovascular abnormalities on disability-free life expectancy (6.45 years [5.90, 6.99] vs 6.96 years [6.43, 7.48]; p = .016). These results were consistent for severe disability-free life expectancy and in individuals without clinical cardiovascular disease.Considering both microvascular and macrovascular abnormalities from multiple noninvasive tests may provide additional prognostic information on how older adults spend their remaining life. Optimal clinical use of this information remains to be determined.

    View details for PubMedID 24864308

  • Risk factors for cardiovascular disease across the spectrum of older age: The Cardiovascular Health Study ATHEROSCLEROSIS Odden, M. C., Shlipak, M. G., Whitson, H. E., Katz, R., Kearney, P. M., defilippi, C., Shastri, S., Sarnak, M. J., Siscovick, D. S., Cushman, M., Psaty, B. M., Newman, A. B. 2014; 237 (1): 336?42

    Abstract

    The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age.Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP).There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45).The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.

    View details for PubMedID 25303772

  • Uric Acid Levels, Kidney Function, and Cardiovascular Mortality in US Adults: National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2002 AMERICAN JOURNAL OF KIDNEY DISEASES Odden, M. C., Amadu, A., Smit, E., Lo, L., Peralta, C. A. 2014; 64 (4): 550?57

    Abstract

    Chronic kidney disease (CKD) and hyperuricemia often coexist, and both conditions are increasing in prevalence in the United States. However, their shared role in cardiovascular risk remains highly debated.Cross-sectional and longitudinal.Participants in the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2002 (n = 10,956); data were linked to mortality data from the National Death Index through December 31, 2006.Serum uric acid concentration, categorized as the sex-specific lowest (< 25th), middle (25th- < 75th), and highest (? 75th) percentiles; and kidney function assessed by estimated glomerular filtration rate (eGFR) based on the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation and urinary albumin-creatinine ratio (ACR).Cardiovascular death and all-cause mortality.Uric acid levels were correlated with eGFR(cr-cys) (r = -0.29; P < 0.001) and were correlated only slightly with ACR (r = 0.04; P < 0.001). There were 2,203 deaths up until December 31, 2006, of which 981 were due to cardiovascular causes. Overall, there was a U-shaped association between uric acid levels and cardiovascular mortality in both women and men, although the lowest risk of cardiovascular mortality occurred at a lower level of uric acid for women compared with men. There was an association between the highest quartile of uric acid level and cardiovascular mortality even after adjustment for potential confounders (HR, 1.48; 95% CI, 1.13-1.96), although this association was attenuated after adjustment for ACR and eGFR(cr-cys) (HR, 1.25; 95% CI, 0.89-1.75). The pattern of association between uric acid levels and all-cause mortality was similar.GFR not measured; mediating events were not observed.High uric acid level is associated with cardiovascular and all-cause mortality, although this relationship was no longer statistically significant after accounting for kidney function.

    View details for PubMedID 24906981

  • Systolic and Diastolic Blood Pressure, Incident Cardiovascular Events, and Death in Elderly Persons The Role of Functional Limitation in the Cardiovascular Health Study HYPERTENSION Peralta, C. A., Katz, R., Newman, A. B., Psaty, B. M., Odden, M. C. 2014; 64 (3): 472?80

    Abstract

    Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78±5 and 21% reported limitation in ?1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP ?65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of ?65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders.

    View details for PubMedID 24935945

  • Subclinical Vascular Disease Burden and Longer Survival JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Odden, M. C., Yee, L. M., Arnold, A. M., Sanders, J. L., Hirsch, C., deFilippi, C., Kizer, J. R., Inzitari, M., Newman, A. B. 2014; 62 (9): 1692?98

    Abstract

    To determine the contribution of gradations of subclinical vascular disease (SVD) to the likelihood of longer survival and to determine what allows some individuals with SVD to live longer.Cohort study.Cardiovascular Health Study.Individuals born between June 30, 1918, and June 30, 1921 (N = 2,082; aged 70-75 at baseline (1992-93)).A SVD index was scored as 0 for no abnormalities, 1 for mild abnormalities, and 2 for severe abnormalities on ankle-arm index, electrocardiogram, and common carotid intima-media thickness measured at baseline. Survival groups were categorized as 80 and younger, 81 to 84, 85 to 89, and 90 and older.A 1-point lower SVD score was associated with 1.22 greater odds (95% confidence interval = 1.14-1.31) of longer survival, independent of potential confounders. This association was unchanged after adjustment for intermediate incident cardiovascular events. There was suggestion of an interaction between kidney function, smoking, and C-reactive protein and SVD; the association between SVD and longer survival appeared to be modestly greater in persons with poor kidney function, inflammation, or a history of smoking.A lower burden of SVD is associated with longer survival, independent of intermediate cardiovascular events. Abstinence from smoking, better kidney function, and lower inflammation may attenuate the effects of higher SVD and promote longer survival.

    View details for PubMedID 25243681

  • Kidney Function and Cognitive Health in Older Adults: The Cardiovascular Health Study AMERICAN JOURNAL OF EPIDEMIOLOGY Darsie, B., Shlipak, M. G., Sarnak, M. J., Katz, R., Fitzpatrick, A. L., Odden, M. C. 2014; 180 (1): 68?75

    Abstract

    Recent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study who were recruited from 4 US communities and studied from 1992 to 1999. Kidney function was measured by cystatin C-based estimated glomerular filtration rate (eGFRcys). Cognitive function was assessed using the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test, which were administered up to 7 times during annual visits. There was an association between eGFRcys and change in cognitive function after adjustment for confounders; persons with an eGFRcys of less than 60 mL/minute/1.73 m(2) had a 0.64 (95% confidence interval: 0.51, 0.77) points/year faster decline in Modified Mini-Mental State Examination score and a 0.42 (95% confidence interval: 0.28, 0.56) points/year faster decline in Digit Symbol Substitution Test score compared with persons with an eGFRcys of 90 or more mL/minute/1.73 m(2). Additional adjustment for intermediate cardiovascular events modestly affected these associations. Participants with an eGFRcys of less than 60 mL/minute/1.73 m(2) had fewer cognitive impairment-free life-years on average compared with those with eGFRcys of 90 or more mL/minute/1.73 m(2), independent of confounders and mediating cardiovascular events (mean difference = -0.44, 95% confidence interval: -0.62, -0.26). Older adults with lower kidney function are at higher risk of worsening cognitive function.

    View details for DOI 10.1093/aje/kwu102

    View details for Web of Science ID 000339808200010

    View details for PubMedID 24844846

    View details for PubMedCentralID PMC4070934

  • Trends in Hypertension Prevalence, Awareness, Treatment, and Control Among US Adults 80 Years and Older, 1988-2010 JOURNAL OF CLINICAL HYPERTENSION Bromfield, S. G., Bowling, C., Tanner, R. M., Peralta, C. A., Odden, M. C., Oparil, S., Muntner, P. 2014; 16 (4): 270?76

    Abstract

    The authors examined trends in systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the prevalence, awareness, treatment, and control of hypertension in 1988-1994 (n=1164), 1999-2004 (n=1,026), and 2005-2010 (n=1048) among US adults 80 years and older in serial National Health and Nutrition Examination Surveys. Hypertension was defined as SBP ?140 mm Hg, DBP ?90 mm Hg, or use of antihypertensive medication. Awareness and treatment were defined by self-report and control as SBP/DBP<140/90 mm Hg. Mean SBP decreased from 147.3 mm Hg to 140.1 mm Hg and mean DBP from 70.2 mm Hg to 59.4 mm Hg between 1988-1994 and 2005-2010. The prevalence, awareness, and treatment of hypertension each increased over time. Controlled hypertension increased from 30.4% in 1988-1994 to 53.1% in 2005-2010. The proportion of patients taking ?3 classes of antihypertensive medication increased from 7.0% to 30.9% between 1988-1994 and 2005-2010. Increases in awareness, treatment, and control of hypertension and antihypertensive polypharmacy have been observed among very old US adults.

    View details for DOI 10.1111/jch.12281

    View details for Web of Science ID 000334290700012

    View details for PubMedID 24621268

  • Health Benefits of Reducing Sugar-Sweetened Beverage Intake in High Risk Populations of California: Results from the Cardiovascular Disease (CVD) Policy Model PLOS ONE Mekonnen, T. A., Odden, M. C., Coxson, P. G., Guzman, D., Lightwood, J., Wang, Y., Bibbins-Domingo, K. 2013; 8 (12): e81723

    Abstract

    Consumption of sugar-sweetened beverage (SSB) has risen over the past two decades, with over 10 million Californians drinking one or more SSB per day. High SSB intake is associated with risk of type 2 diabetes, obesity, hypertension, and coronary heart disease (CHD). Reduction of SSB intake and the potential impact on health outcomes in California and among racial, ethnic, and low-income sub-groups has not been quantified.We projected the impact of reduced SSB consumption on health outcomes among all Californians and California subpopulations from 2013 to 2022. We used the CVD Policy Model - CA, an established computer simulation of diabetes and heart disease adapted to California. We modeled a reduction in SSB intake by 10-20% as has been projected to result from proposed penny-per-ounce excise tax on SSB and modeled varying effects of this reduction on health parameters including body mass index, blood pressure, and diabetes risk. We projected avoided cases of diabetes and CHD, and associated health care cost savings in 2012 US dollars.Over the next decade, a 10-20% SSB consumption reduction is projected to result in a 1.8-3.4% decline in the new cases of diabetes and an additional drop of 0.5-1% in incident CHD cases and 0.5-0.9% in total myocardial infarctions. The greatest reductions are expected in African Americans, Mexican Americans, and those with limited income regardless of race and ethnicity. This reduction in SSB consumption is projected to yield $320-620 million in medical cost savings associated with diabetes cases averted and an additional savings of $14-27 million in diabetes-related CHD costs avoided.A reduction of SSB consumption could yield substantial population health benefits and cost savings for California. In particular, racial, ethnic, and low-income subgroups of California could reap the greatest health benefits.

    View details for PubMedID 24349119

  • Kidney Function and Prevalent and Incident Frailty CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Dalrymple, L. S., Katz, R., Rifkin, D. E., Siscovick, D., Newman, A. B., Fried, L. F., Sarnak, M. J., Odden, M. C., Shlipak, M. G. 2013; 8 (12): 2091?99

    Abstract

    Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants.CHS enrolled community-dwelling adults age ?65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity.The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) ?90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty.In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.

    View details for DOI 10.2215/CJN.02870313

    View details for Web of Science ID 000327951100010

    View details for PubMedID 24178972

    View details for PubMedCentralID PMC3848393

  • Hypertension and low HDL cholesterol were associated with reduced kidney function across the age spectrum: a collaborative study ANNALS OF EPIDEMIOLOGY Odden, M. C., Tager, I. B., Gansevoort, R. T., Bakker, S. L., Fried, L. F., Newman, A. B., Katz, R., Satterfield, S., Harris, T. B., Sarnak, M. J., Siscovick, D., Shlipak, M. G. 2013; 23 (3): 106?11

    Abstract

    To determine if the associations among established risk factors and reduced kidney function vary by age.We pooled cross-sectional data from 14,788 nondiabetics aged 40 to 100 years in 4 studies: Cardiovascular Health Study, Health, Aging, and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-Stage Disease cohort.Hypertension and low high-density lipoprotein (HDL) cholesterol were associated with reduced cystatin C-based estimated glomerular filtration rate (eGFR) across the age spectrum. In adjusted analyses, hypertension was associated with a 2.3 (95% confidence interval [CI], 0.1, 4.4), 5.1 (95% CI, 4.1, 6.1), and 6.9 (95% CI, 3.0, 10.4) mL/min/1.73 m(2) lower eGFR in participants 40 to 59, 60 to 79, and at least 80 years, respectively (P for interaction < .001). The association of low HDL cholesterol with reduced kidney function was also greater in the older age groups: 4.9 (95% CI, 3.5, 6.3), 7.1 (95% CI, 6.0, 8.3), 8.9 (95% CI, 5.4, 11.9) mL/min/1.73 m(2) (P for interaction < .001). Smoking and obesity were associated with reduced kidney function in participants under 80 years. All estimates of the potential population impact of the risk factors were modest.Hypertension, obesity, smoking, and low HDL cholesterol are modestly associated with reduced kidney function in nondiabetics. The associations of hypertension and HDL cholesterol with reduced kidney function seem to be stronger in older adults.

    View details for PubMedID 23313266

  • THE ASSOCIATION OF RESILIENCE WITH MENTAL AND PHYSICAL HEALTH AMONG OLDER AMERICAN INDIANS: THE NATIVE ELDER CARE STUDY AMERICAN INDIAN AND ALASKA NATIVE MENTAL HEALTH RESEARCH Schure, M. B., Odden, M., Goins, R. 2013; 20 (2): 27?41

    Abstract

    We examined the association of resilience with measures of mental and physical health in a sample of older American Indians (AIs). A validated scale measuring resilience was administered to 185 noninstitutionalized AIs aged>=55 years. Unadjusted analyses revealed that higher levels of resilience were associated with lower levels of depressive symptomatology and chronic pain, and with higher levels of mental and physical health. Resilience remained significantly associated with depressive symptomatology after controlling for demographic and other health measures. Our findings suggest that resilience among older AIs has important implications for some aspects of mental and physical health.

    View details for Web of Science ID 000322082700002

    View details for PubMedID 23824641

    View details for PubMedCentralID PMC3805026

  • Association Between Chronic Kidney Disease Detected Using Creatinine and Cystatin C and Death and Cardiovascular Events in Elderly Mexican Americans: The Sacramento Area Latino Study on Aging JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Peralta, C. A., Lee, A., Odden, M. C., Lopez, L., Al Hazzouri, A., Neuhaus, J., Haan, M. N. 2013; 61 (1): 90?95

    Abstract

    Creatinine, the current clinical standard to detect chronic kidney disease (CKD), is biased by muscle mass, age and race. The authors sought to determine whether cystatin C, an alternative marker of kidney function less biased by these factors, can identify elderly Mexican Americans with CKD who are at high risk for death and cardiovascular disease.Longitudinal, with mean follow-up of 6.8 years.Sacramento Area Latino Study of Aging (SALSA).One thousand four hundred and thirty five Mexican Americans aged 60 to 101.Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was determined according to creatinine (eGFRcreat) and cystatin C (eGFRcys), and participants were classified into four mutually exclusive categories: CKD neither (eGFRcreat ?60 mL/min per 1.73 m(2); eGFRcys ?60 mL/min per 1.73 m(2)), CKD creatinine only (eGFRcreat <60 mL/min per 1.73 m(2); eGFRcys ?60 mL/min per 1.73 m(2)), CKD cystatin only (eGFRcreat ?60 mL/min per 1.73 m(2); eGFRcys <60), and CKD both (eGFRcreat <60 mL/min per 1.73 m(2); GFRcys <60 mL/min per 1.73 m(2)). The associations between each CKD classification and all-cause death and cardiovascular (CV) death were studied using Cox regression.At baseline, mean age was 71 ± 7; 481 (34%) had diabetes mellitus, and 980 (68%) had hypertension. Persons with CKD both had higher risk for all-cause (HR = 2.30, 95% confidence interval (CI) = 1.78-2.98) and CV disease (CVD) (HR = 2.75, 95% CI = 1.96-3.86) death than CKD neither after full adjustment. Persons with CKD cystatin C only were also at greater risk of all-cause (HR = 1.91, 95% CI = 1.37-2.67) and CV (HR = 2.56, 95% CI = 1.64-3.99) death than CKD neither. In contrast, persons with CKD creatinine only were not at greater risk for CV death (HR = 1.39, 95% CI = 0.71-2.72) but were at higher risk for all-cause death (HR = 1.95, 95% CI = 1.27-2.98).Cystatin C may be a useful alternative to creatinine for detecting high risk of death and CVD in elderly Mexican Americans with CKD.

    View details for DOI 10.1111/jgs.12040

    View details for Web of Science ID 000313715600016

    View details for PubMedID 23252993

    View details for PubMedCentralID PMC3545054

  • The Association of Blood Pressure and Mortality Differs by Self-reported Walking Speed in Older Latinos JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Odden, M. C., Covinsky, K. E., Neuhaus, J. M., Mayeda, E. R., Peralta, C. A., Haan, M. N. 2012; 67 (9): 977?83

    Abstract

    In some older adults, higher blood pressure (BP) is associated with a lower risk of mortality. We hypothesized that higher BP would be associated with greater mortality in high-functioning elders and lower mortality in elders with lower functional status.Participants were 1,562 Latino adults aged 60-101 years in the Sacramento Area Latino Study on Aging. Functional status was measured by self-reported walking speed, and BP was measured by automatic sphygmomanometer. Death information was determined from vital statistics records.There were 442 deaths from 1998 to 2010; 53% were cardiovascular. Mean BP levels (mmHg) varied across fast, medium, and slow walkers: 136, 139, and 140 mmHg (systolic), p = .02 and 75, 76, and 77 mmHg (diastolic), p = .08, respectively. The relationship between systolic BP and mortality varied by self-reported walking speed: The adjusted hazard ratio for mortality in slow walkers was 0.96 per 10 mmHg higher systolic BP (95% confidence interval: 0.89, 1.02) and 1.29 (95% confidence interval: 1.08, 1.55) in fast walkers (p value for interaction <.001). We found a similar pattern for diastolic BP, although the interaction did not reach statistical significance; the adjusted hazard ratio per 10 mmHg higher diastolic BP was 0.89 (95% confidence interval: 0.78, 1.02) in slow walkers and 1.20 (95% confidence interval: 0.82, 1.76) in fast walkers (p value for interaction = .06).In high-functioning older adults, elevated systolic BP is a risk factor for all-cause mortality. If confirmed in other studies, the assessment of functional status may help to identify persons who are most at-risk for adverse outcomes related to high BP.

    View details for PubMedID 22389463

  • Rethinking the Association of High Blood Pressure With Mortality in Elderly Adults The Impact of Frailty ARCHIVES OF INTERNAL MEDICINE Odden, M. C., Peralta, C. A., Haan, M. N., Covinsky, K. E. 2012; 172 (15): 1162?68

    Abstract

    The association of hypertension and mortality is attenuated in elderly adults. Walking speed, as a measure of frailty, may identify which elderly adults are most at risk for the adverse effects of hypertension. We hypothesized that elevated blood pressure (BP) would be associated with a greater risk of mortality in faster-, but not slower-, walking older adults.Participants included 2340 persons 65 years and older in the National Health and Nutrition Examination Survey, 1999-2000 and 2001-2002. Mortality data were linked to death certificates in the National Death Index. Walking speed was measured over a 20-ft (6 m) walk and classified as faster (? 0.8 m/s [n = 1307]), slower (n = 790), or incomplete (n = 243). Potential confounders included age, sex, race, survey year, lifestyle and physiologic variables, health conditions, and antihypertensive medication use.Among the participants, there were 589 deaths through December 31, 2006. The association between BP and mortality varied by walking speed. Among faster walkers, those with elevated systolic BP (? 140 mm Hg) had a greater adjusted risk of mortality compared with those without (hazard ratio [HR], 1.35; 95% CI, 1.03-1.77). Among slower walkers, neither elevated systolic nor diastolic BP (? 90 mm Hg) was associated with mortality. In participants who did not complete the walk test, elevated BP was strongly and independently associated with a lower risk of death: HR, 0.38; 95% CI, 0.23-0.62 (systolic); and HR, 0.10; 95% CI, 0.01-0.81 (diastolic).Walking speed could be a simple measure to identify elderly adults who are most at risk for adverse outcomes related to high BP.

    View details for PubMedID 22801930

  • Kidney Function and Mortality in Octogenarians: Cardiovascular Health Study All Stars JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Shastri, S., Katz, R., Rifkin, D. E., Fried, L. F., Odden, M. C., Peralta, C. A., Chonchol, M., Siscovick, D., Shlipak, M. G., Newman, A. B., Sarnak, M. J. 2012; 60 (7): 1201?7

    Abstract

    To examine the association between kidney function and all-cause mortality in octogenarians.Retrospective analysis of prospectively collected data.Community.Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants.Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFR(CR) ) and cystatin C one-variable (eGFR(CYS) ) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models.Mean age of the participants was 85, 64% were female, 66% had hypertension, 14% had diabetes mellitus, and 39% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFR(CR) and all-cause mortality was U-shaped. In comparison with the reference quintile (64-75 mL/min per 1.73 m(2) ), the highest (? 75 mL/min per 1.73 m(2) ) and lowest (? 43 mL/min per 1.73 m(2) ) quintiles of eGFR(CR) were independently associated with mortality (hazard ratio (HR) = 2.49, 95% confidence interval (CI) = 1.36-4.55; HR = 2.28, 95% CI = 1.26-4.10, respectively). The association between eGFR(CYS) and all-cause mortality was linear in those with eGFR(CYS) of less than 60 mL/min per 1.73 m(2) , and in the multivariate analyses, the lowest quintile of eGFR(CYS) (<52 mL/min per 1.73 m(2) ) was significantly associated with mortality (HR = 2.04, 95% CI = 1.12-3.71) compared with the highest quintile (>0.88 mL/min per 1.73 m(2) ).Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFR(CR) and all-cause mortality differed from that observed with eGFR(CYS) ; the relationship was U-shaped for eGFR(CR) , whereas the risk was primarily present in the lowest quintile for eGFR(CYS) .

    View details for DOI 10.1111/j.1532-5415.2012.04046.x

    View details for Web of Science ID 000306311600001

    View details for PubMedID 22724391

    View details for PubMedCentralID PMC3902776

  • The Impact of the Aging Population on Coronary Heart Disease in the United States AMERICAN JOURNAL OF MEDICINE Odden, M. C., Coxson, P. G., Moran, A., Lightwood, J. M., Goldman, L., Bibbins-Domingo, K. 2011; 124 (9): 827-U1506

    Abstract

    The demographic shift toward an older population in the United States will result in a higher burden of coronary heart disease, but the increase has not been quantified in detail. We sought to estimate the impact of the aging US population on coronary heart disease.We used the Coronary Heart Disease Policy Model, a Markov model of the US population between 35 and 84 years of age, and US Census projections to model the age structure of the population between 2010 and 2040.Assuming no substantive changes in risks factors or treatments, incident coronary heart disease is projected to increase by approximately 26%, from 981,000 in 2010 to 1,234,000 in 2040, and prevalent coronary heart disease by 47%, from 11.7 million to 17.3 million. Mortality will be affected strongly by the aging population; annual coronary heart disease deaths are projected to increase by 56% over the next 30 years, from 392,000 to 610,000. Coronary heart disease-related health care costs are projected to rise by 41% from $126.2 billion in 2010 to $177.5 billion in 2040 in the United States. It may be possible to offset the increase in disease burden through achievement of Healthy People 2010/2020 objectives or interventions that substantially reduce obesity, blood pressure, or cholesterol levels in the population.Without considerable changes in risk factors or treatments, the aging of the US population will result in a sizeable increase in coronary heart disease incidence, prevalence, mortality, and costs. Health care stakeholders need to plan for the future age-related health care demands of coronary heart disease.

    View details for DOI 10.1016/j.amjmed.2011.04.010

    View details for Web of Science ID 000294043100025

    View details for PubMedID 21722862

    View details for PubMedCentralID PMC3159777

  • Longitudinal Association of Depressive Symptoms with Rapid Kidney Function Decline and Adverse Clinical Renal Disease Outcomes CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kop, W. J., Seliger, S. L., Fink, J. C., Katz, R., Odden, M. C., Fried, L. F., Rifkin, D. E., Sarnak, M. J., Gottdiener, J. S. 2011; 6 (4): 834?44

    Abstract

    Depression is a risk indicator for adverse outcomes in dialysis patients, but its prognostic impact in individuals who are not yet on dialysis is unknown. This study examines whether depressive symptoms are longitudinally associated with renal function decline, new-onset chronic kidney disease (CKD), ESRD, or hospitalization with acute kidney injury (AKI).Depressive symptoms were measured in a longitudinal cohort study with the 10-item Centers for Epidemiologic Studies Depression scale using a previously validated cut-off value (?8). CKD at study entry and during follow-up was defined as an estimated GFR (eGFR) < 60 ml/min per m(2). Outcomes were rapid decline in eGFR (>3 ml/min per m(2) per year), new-onset CKD, ESRD (U.S. Renal Data System-based), and AKI (based on adjudicated medical record review). The median follow-up duration was 10.5 years.Depressed participants (21.2%) showed a higher prevalence of CKD at baseline compared with nondepressed participants in multivariable analysis. Depression was associated with a subsequent risk of rapid decline in eGFR, incident ESRD, and AKI, but not incident CKD in unadjusted models. In multivariable analyses, only associations of depressive symptoms with AKI remained significant.Elevated depressive symptoms are associated with subsequent adverse renal disease outcomes. The depression-related elevated risk of AKI was independent of traditional renal disease risk factors and may in part be explained by the predictive value of depression for acute coronary syndromes and heart failure hospitalizations that can be complicated by AKI.

    View details for DOI 10.2215/CJN.03840510

    View details for Web of Science ID 000289223600022

    View details for PubMedID 21393483

    View details for PubMedCentralID PMC3069377

  • Antihypertensive Medication Use and Change in Kidney Function in Elderly Adults: A Marginal Structural Model Analysis INTERNATIONAL JOURNAL OF BIOSTATISTICS Odden, M. C., Tager, I. B., van der Laan, M. J., Delaney, J. C., Peralta, C. A., Katz, R., Sarnak, M. J., Psaty, B. M., Shlipak, M. G. 2011; 7 (1): Article 34

    Abstract

    The evidence for the effectiveness of antihypertensive medication use for slowing decline in kidney function in older persons is sparse. We addressed this research question by the application of novel methods in a marginal structural model.Change in kidney function was measured by two or more measures of cystatin C in 1,576 hypertensive participants in the Cardiovascular Health Study over 7 years of follow-up (1989-1997 in four U.S. communities). The exposure of interest was antihypertensive medication use. We used a novel estimator in a marginal structural model to account for bias due to confounding and informative censoring.The mean annual decline in eGFR was 2.41 ± 4.91 mL/min/1.73 m(2). In unadjusted analysis, antihypertensive medication use was not associated with annual change in kidney function. Traditional multivariable regression did not substantially change these estimates. Based on a marginal structural analysis, persons on antihypertensives had slower declines in kidney function; participants had an estimated 0.88 (0.13, 1.63) ml/min/1.73 m(2) per year slower decline in eGFR compared with persons on no treatment. In a model that also accounted for bias due to informative censoring, the estimate for the treatment effect was 2.23 (-0.13, 4.59) ml/min/1.73 m(2) per year slower decline in eGFR.In summary, estimates from a marginal structural model suggested that antihypertensive therapy was associated with preserved kidney function in hypertensive elderly adults. Confirmatory studies may provide power to determine the strength and validity of the findings.

    View details for PubMedID 22049266

  • Physical Functioning in Elderly Persons With Kidney Disease ADVANCES IN CHRONIC KIDNEY DISEASE Odden, M. C. 2010; 17 (4): 348?57

    Abstract

    Poor physical functioning in dialysis patients has been well documented. Several studies have reported an association of poor kidney function with adverse physical functioning outcomes, even in elderly persons with mild decrements in kidney function. These associations have been observed across multiple domains of physical function. This review summarizes the current research on physical functioning in kidney disease, with a special focus on elderly populations. Elderly persons with kidney disease may especially be at a high risk for disability and other adverse outcomes because of the dual effects of aging and kidney dysfunction on physical functioning. Both the correction of anemia and physical activity are effective for at least moderate improvements in physical function although these studies have been conducted primarily in younger persons with less comorbidity. The evidence that exists on exercise interventions in older adults with kidney disease is promising, although this population has been underrepresented in trials to date. More research on potential interventions to prevent or reduce poor physical functioning is needed in elderly persons with kidney disease.

    View details for DOI 10.1053/j.ackd.2010.02.002

    View details for Web of Science ID 000279804000009

    View details for PubMedID 20610362

  • Age and cystatin C in healthy adults: a collaborative study NEPHROLOGY DIALYSIS TRANSPLANTATION Odden, M. C., Tager, I. B., Gansevoort, R. T., Bakker, S. L., Katz, R., Fried, L. F., Newman, A. B., Canada, R. B., Harris, T., Sarnak, M. J., Siscovick, D., Shlipak, M. G. 2010; 25 (2): 463?69

    Abstract

    Kidney function declines with age, but a substantial portion of this decline has been attributed to the higher prevalence of risk factors for kidney disease at older ages. The effect of age on kidney function has not been well described in a healthy population across a wide age spectrum.The authors pooled individual-level cross-sectional data from 18 253 persons aged 28-100 years in four studies: the Cardiovascular Health Study; the Health, Aging and Body Composition Study; the Multi-Ethnic Study of Atherosclerosis and the Prevention of Renal and Vascular End-Stage Disease cohort. Kidney function was measured by cystatin C. Clinical risk factors for kidney disease included diabetes, hypertension, obesity, smoking, coronary heart disease, cerebrovascular disease, peripheral arterial disease and heart failure.Across the age range, there was a strong, non-linear association of age with cystatin C concentration. This association was substantial, even among participants free of clinical risk factors for kidney disease; mean cystatin C levels were 46% higher in participants 80 and older compared with those <40 years (1.06 versus 0.72 mg/L, P < 0.001). Participants with one or more risk factors had higher cystatin C concentrations for a given age, and the age association was slightly stronger (P < 0.001 for age and risk factor interaction).There is a strong, non-linear association of age with kidney function, even in healthy individuals. An important area for research will be to investigate the mechanisms that lead to deterioration of kidney function in apparently healthy persons.

    View details for DOI 10.1093/ndt/gfp474

    View details for Web of Science ID 000273891600024

    View details for PubMedID 19749145

    View details for PubMedCentralID PMC2904248

  • Serum Creatinine and Functional Limitation in Elderly Persons JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Odden, M. C., Shlipak, M. G., Tager, I. B. 2009; 64 (3): 370?76

    Abstract

    Creatinine is a commonly used measure of kidney function, but serum levels are also influenced by muscle mass. We hypothesized that higher serum creatinine would be associated with self-reported functional limitation in community-dwelling elderly.Subjects (n = 1,553) were participants in the Study of Physical Performance and Age-Related Changes in Sonomans, a cohort to study aging and physical function. We explored three strategies to account for the effects of muscle mass on serum creatinine.We observed a J-shaped association of creatinine with functional limitation. Above the study-specific mean creatinine (0.97 mg/dL in women and 1.15 mg/dL in men), the unadjusted odds ratio of functional limitation per standard deviation (0.20 mg/dL in women and 0.23 mg/dL in men) higher creatinine was 2.27 (95% confidence interval [CI] 1.75-2.94, p < .001) in women and 1.42 (95% CI 1.12-1.80, p = .003) in men. This association was inverted in persons with creatinine levels below the mean. Adjustment for muscle mass did not have an important effect on the association between creatinine and functional limitation. These associations remained after multivariable adjustment for demographics and health conditions but were statistically significant only in women.In elderly adults, higher creatinine levels are associated with functional limitation, consistent with prior literature that has demonstrated reduced physical performance in persons with kidney disease. However, the association of low creatinine levels with functional limitation suggests that creatinine levels are influenced by factors other than kidney function and muscle mass in the elderly.

    View details for DOI 10.1093/gerona/gln037

    View details for Web of Science ID 000264190500006

    View details for PubMedID 19181716

    View details for PubMedCentralID PMC2655007

  • Health, aging, and body composition study: Diabetes-related complications, glycemic control, and falls in older adults (vol 31, pg 391, 2008) DIABETES CARE Schwartz, A., Vittinghoff, E., Sellmeyer, D. E., Feingold, K. R., de Rekeneire, N., Strotmeyer, E. S., Shorr, R., Vinik, A., Odden, M. C., Park, S. W., Faulkner, K. A., Harris, T. B., Health Aging Body Composition 2008; 31 (5): 1089
  • Diabetes-related complications, glycemic control, and falls in older adults Schwartz, A. V., Vittinghoff, E., Sellmeyer, D. E., Feingold, K. R., de Rekeneire, N., Strotmeyer, E. S., Shorr, R. I., Vinik, A. I., Odden, M. C., Park, S., Faulkner, K. A., Harris, T. B., Hlth Aging Body Composition Study AMER DIABETES ASSOC. 2008: 391?96

    Abstract

    Older adults with type 2 diabetes are more likely to fall, but little is known about risk factors for falls in this population. We determined whether diabetes-related complications or treatments are associated with risk of falls in older diabetic adults.In the Health, Aging, and Body Composition cohort of well-functioning older adults, participants reported falls in the previous year at annual visits. Odds ratios (ORs) for more frequent falls among 446 diabetic participants whose mean age was 73.6 years, with an average follow-up of 4.9 years, were estimated with continuation ratio models.In the first year, 23[corrected]% reported falling; 22, 26, 30[corrected], and 31[corrected]% fell in subsequent years. In adjusted models, reduced peroneal nerve response amplitude (OR 1.50 -95% CI 1.07-2.12], worst quartile versus others); higher cystatin-C, a marker of reduced renal function (1.38 [1.11-1.71], for 1 SD increase); poorer contrast sensitivity (1.41 [0.97-2.04], worst quartile versus others); and low A1C in insulin users (4.36 [1.32-14.46], A1C 8%) were associated with risk of falls. In those using oral hypoglycemic medications but not insulin, low A1C was not associated with risk of falls (1.29 [0.65-2.54], A1C 8%). Adjustment for physical performance explained some, but not all, of these associations.In older diabetic adults, reducing diabetes-related complications may prevent falls. Achieving lower A1C levels with oral hypoglycemic medications was not associated with more frequent falls, but, among those using insulin, A1C

    View details for DOI 10.2337/dc07-1152

    View details for Web of Science ID 000253801100003

    View details for PubMedID 18056893

    View details for PubMedCentralID PMC2288549

  • Cystatin C level as a marker of kidney function in human immunodeficiency virus infection - The FRAM study ARCHIVES OF INTERNAL MEDICINE Odden, M. C., Scherzer, R., Bacchetti, P., Szczech, L., Sidney, S., Grunfeld, C., Shlipak, M. G. 2007; 167 (20): 2213?19

    Abstract

    Although studies have reported a high prevalence of end-stage renal disease in human immunodeficiency virus (HIV)-infected individuals, little is known about moderate impairments in kidney function. Cystatin C measurement may be more sensitive than creatinine for detecting impaired kidney function in persons with HIV.We evaluated kidney function in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) cohort, a representative sample of 1008 HIV-infected persons and 290 controls from the Coronary Artery Risk Development in Young Adults (CARDIA) study in the United States.Cystatin C level was elevated in HIV-infected individuals; the mean +/- SD cystatin C level was 0.92 +/- 0.22 mg/L in those infected with HIV and 0.76 +/- 0.15 mg/L in controls (P < .001). In contrast, both mean creatinine levels and estimated glomerular filtration rates appeared similar in HIV-infected individuals and controls (0.87 +/- 0.21 vs 0.85 +/- 0.19 mg/dL [to convert to micromoles per liter, multiply by 88.4] [P = .35] and 110 +/- 26 vs 106 +/- 23 mL/min/1.73 m(2) [P = .06], respectively). Persons with HIV infection were more likely to have a cystatin C level greater than 1.0 mg/L (OR, 9.8; 95% confidence interval, 4.4-22.0 [P <.001]), a threshold demonstrated to be associated with increased risk for death and cardiovascular and kidney disease. Among participants with HIV, potentially modifiable risk factors for kidney disease, hypertension, and low high-density lipoprotein concentration were associated with a higher cystatin C level, as were lower CD4 lymphocyte count and coinfection with hepatitis C virus (all P < .001).Individuals infected with HIV had substantially worse kidney function when measured by cystatin C level compared with HIV-negative controls, whereas mean creatinine levels and estimated glomerular filtration rates were similar. Cystatin C measurement could be a useful clinical tool to identify HIV-infected persons at increased risk for kidney and cardiovascular disease.

    View details for DOI 10.1001/archinte.167.20.2213

    View details for Web of Science ID 000250806200008

    View details for PubMedID 17998494

    View details for PubMedCentralID PMC3189482

  • Kidney function and markers of inflammation in elderly persons without chronic kidney disease: The health, aging, and body composition study KIDNEY INTERNATIONAL Keller, C. R., Odden, M. C., Fried, L. F., Newman, A. B., Angleman, S., Green, C. A., Cummings, S. R., Harris, T. B., Shlipak, M. G. 2007; 71 (3): 239?44

    Abstract

    Inflammatory markers are elevated in persons with estimated glomerular filtration rates less than 60 ml/min/1.73 m2. As cystatin C may detect small changes in kidney function not detected by estimated glomerular filtration rate, we evaluated the association between cystatin C and serum markers of inflammation in older adults with estimated glomerular filtration rate >or=60. This is an analysis using measures from the Health, Aging, and Body Composition Study, a cohort of well-functioning adults aged 70-79 years. Cystatin C correlated with all five inflammatory biomarkers: C-reactive protein (r=0.08), interleukin-6 (r=0.19), tumor necrosis factor alpha (TNF-alpha) (r=0.41), soluble TNF receptor 1 (STNF-R1) (r=0.61), and soluble TNF receptor 2 (STNF-R2) (r=0.54); P<0.0005 for all. In adjusted analyses, cystatin C concentrations appeared to have stronger associations with each biomarker compared with estimated glomerular filtration rate or serum creatinine. Participants with a cystatin C>or=1.0 mg/l had significantly higher levels of all five biomarkers compared to those with a cystatin C<1.0 (mean differences ranging 16-29%, all P<0.05). Cystatin C has a linear association with inflammatory biomarkers in an ambulatory elderly cohort with estimated glomerular filtration rates >or=60; associations are particularly strong with TNF-alpha and the STNF-R.

    View details for DOI 10.1038/sj.ki.5002042

    View details for Web of Science ID 000243730800011

    View details for PubMedID 17183246

  • Cystatin C and measures of physical function in elderly adults - The health, aging, and body composition (HABC) study AMERICAN JOURNAL OF EPIDEMIOLOGY Odden, M. C., Chertow, G. M., Fried, L. F., Newman, A. B., Connelly, S., Angleman, S., Harris, T. B., Simonsick, E. M., Shlipak, M. G. 2006; 164 (12): 1180-1189

    Abstract

    Most studies of the relation between kidney function and physical function have been conducted in persons with advanced kidney disease and have used creatinine-based measures of kidney function. Cystatin C concentration is a measure of kidney function that is independent of muscle mass, unlike creatinine. Using baseline data on 3,043 elderly adults from the Health, Aging, and Body Composition Study (Blacks and Whites recruited from Pittsburgh, Pennsylvania, and Memphis, Tennessee, in 1997-1998), the authors examined the cross-sectional association between cystatin C level and performance on several tests of physical function. After adjustment for demographic and lifestyle variables, chronic health conditions, and inflammation, each standard-deviation (0.34 mg/liter) increase in cystatin C concentration was associated with 1.32 odds (95% confidence interval (CI): 1.20, 1.46) of not completing a 400-m walk, a 10.9-second (95% CI: 8.1, 13.8) slower 400-m walk time, a 0.11-point (95% CI: 0.09, 0.13) reduction in lower extremity performance score, a 1.12-kg (95% CI: 0.83, 1.40) lower grip strength, and a 4.7-nm (95% CI: 3.5, 5.9) lower knee extension strength. In contrast, when kidney function was measured by estimated glomerular filtration rate, the association of kidney function with physical function was only evident below 60 ml/minute/1.73 m2. In these older adults, mild decrements in kidney function, as measured by cystatin C concentration, were associated with poorer physical function.

    View details for DOI 10.1093/aje/kwj333

    View details for Web of Science ID 000242714800006

    View details for PubMedID 17035344

  • Renal function and heart failure risk in older black and white individuals - The health, aging, and body composition study ARCHIVES OF INTERNAL MEDICINE Bibbins-Domingo, K., Chertow, G. M., Fried, L. F., Odden, M. C., Newman, A. B., Kritchevsky, S. B., Harris, T. B., Satterfield, S., Cummings, S. R., Shlipak, M. G. 2006; 166 (13): 1396-1402

    Abstract

    Chronic kidney disease is a risk factor for heart failure, an association that may be particularly important in blacks who are disproportionately affected by both processes. Our objective was to determine whether the association of chronic kidney disease with incident heart failure differs between blacks and whites.The study population comprised participants in the Health, Aging, and Body Composition Study without a diagnosis of heart failure (1124 black and 1676 white community-dwelling older persons). The main predictors were quintiles of cystatin C and creatinine concentrations and estimated glomerular filtration rate. The main outcome measure was incident heart failure.Over a mean 5.7 years, 200 participants developed heart failure. High concentrations of cystatin C and low estimated glomerular filtration rate were each associated with heart failure, but the magnitude was greater for blacks than for whites (cystatin C concentration: adjusted hazard ratio for quintile 5 [> or =1.18 mg/dL] vs quintile 1 [<0.84 mg/dL] was 3.0 [95% confidence interval 1.4-6.5] in blacks and 1.4 [95% confidence interval, 0.8-2.5] in whites; estimated glomerular filtration rate: adjusted hazard ratio for quintile 5 (<59.2 mL/min) vs quintile 1 (>86.7 mL/min) was 2.7 [95% confidence interval, 1.4-4.9] in blacks and 1.8 [95% confidence interval, 0.9-3.6] in whites). For cystatin C, this association was observed at more modest decrements in kidney function among blacks as well. The population attributable risk of heart failure was 47% for blacks with moderate or high concentrations of cystatin C (> or =0.94 mg/dL) (56% prevalence) but only 5% among whites (64% prevalence).The association of kidney dysfunction with heart failure appears stronger in blacks than for whites, particularly when cystatin C is used to measure kidney function.

    View details for Web of Science ID 000238916500009

    View details for PubMedID 16832005

  • Depression, stress, and quality of life in persons with chronic kidney disease: The Heart and Soul Study NEPHRON CLINICAL PRACTICE Odden, M. C., Whooley, M. A., Shlipak, M. G. 2006; 103 (1): C1?C7

    Abstract

    The effect of mild chronic kidney disease (CKD) on depression, stress, quality of life (QOL), and health status is not well understood. We compared these outcomes in subjects with and without CKD.We performed a cross-sectional study of 967 outpatients enrolled in the Heart and Soul Study. CKD was defined as a measured creatinine clearance < 60 ml/min. Outcome measures included depressive symptoms measured using the Patient Health Questionnaire (PHQ), stress measured using the Perceived Stress Scale (PSS), and QOL and overall health rated as excellent, very good, good, fair, or poor.The prevalence of depressive symptoms (17 vs. 19%, p = 0.4) or perceived stress (11 vs. 16%, p = 0.09) did not vary significantly by CKD. The prevalence of fair or poor QOL was not significantly different in subjects with CKD, compared with those without CKD (24 vs. 23%, p = 0.65). Age-adjusted analyses revealed a significant association of CKD with QOL (p = 0.003), however, this association no longer reached statistical significance after adjustment for confounders (p = 0.06). Subjects with CKD were more likely to report poor or fair overall health than subjects without CKD (42 vs. 34%, p = 0.03). After multivariate adjustment, CKD remained significantly associated with worse overall health (OR = 1.65, 95% CI 1.21-2.24, p = 0.001), and modestly associated with QOL (OR = 1.31, 95% CI 0.99-1.75, p = 0.06), but had no association with depression (p = 0.48) or stress (p = 0.24).In this study of persons with coronary artery disease, subjects with CKD had reduced overall health and modestly reduced QOL; however, mental health was similar in those with and without CKD. These findings suggest that self- assessed overall health may decline at earlier stages of renal dysfunction than mental health outcomes or QOL.

    View details for DOI 10.1159/000090112

    View details for Web of Science ID 000246174100001

    View details for PubMedID 16340237

    View details for PubMedCentralID PMC2776701

  • Association of chronic kidney disease and anemia with physical capacity: The heart and soul study JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Odden, M. C., Whooley, M. A., Shlipak, M. G. 2004; 15 (11): 2908?15

    Abstract

    Chronic kidney disease (CKD) and anemia are common conditions in the outpatient setting, but their independent and additive effects on physical capacity have not been well characterized. The association of CKD and anemia with self-reported physical function was evaluated and exercise capacity was measured in patients with coronary disease. A cross-sectional study of 954 outpatients enrolled in the Heart and Soul study was performed. CKD was defined as a measured creatinine clearance <60 ml/min, and anemia was defined as a hemoglobin level of <12g/dl. Physical function was self-assessed using the physical limitation subscale of the Seattle Angina Questionnaire (0 to 100), and exercise capacity was defined as metabolic equivalent tasks achieved at peak exercise. In unadjusted analyses, CKD was associated with lower self-reported physical function (67.6 versus 74.9; P < 0.001) and lower exercise capacity (5.5 versus 7.9; P < 0.001). Similarly, anemia was associated with lower self-reported physical function (62.6 versus 74.3; P < 0.001) and exercise capacity (5.7 versus 7.5; P < 0.001). After multivariate adjustment, CKD (69.4 versus 74.2; P = 0.003) and anemia (67.5 versus 73.6; P = 0.009) each remained associated with lower mean self-reported physical function. In addition, patients with CKD (6.3 versus 7.7; P < 0.001) or anemia (6.5 versus 7.4; P = 0.004) had lower adjusted mean exercise capacities. Participants with both CKD and anemia had lower self-reported physical function and exercise capacity than those with either alone. CKD and anemia are independently associated with physical limitation and reduced exercise capacity in outpatients with coronary disease, and these effects are additive. The broad impact of these disease conditions merits further study.

    View details for DOI 10.1097/01.ASN.0000143743.78092.E3

    View details for Web of Science ID 000224684200016

    View details for PubMedID 15504944

    View details for PubMedCentralID PMC2776664

  • Effect of Opuntia ficus indica on symptoms of the alcohol hangover ARCHIVES OF INTERNAL MEDICINE Wiese, J., McPherson, S., Odden, M. C., Shlipak, M. G. 2004; 164 (12): 1334?40

    Abstract

    The severity of the alcohol hangover may be related to inflammation induced by impurities in the alcohol beverage and byproducts of alcohol metabolism. An extract of the Opuntia ficus indica (OFI) plant diminishes the inflammatory response to stressful stimuli.In this double-blind, placebo-controlled, crossover trial, 64 healthy, young adult volunteers were randomly assigned to receive OFI (1600 IU) and identical placebo, given 5 hours before alcohol consumption. During 4 hours, subjects consumed up to 1.75 g of alcohol per kilogram of body weight. Hangover severity (9 symptoms) and overall well-being were assessed on a scale (0-6), and blood and urine samples were obtained the following morning. Two weeks later, the study protocol was repeated with OFI and placebo reversed.Fifty-five subjects completed both the OFI and placebo arms of the study. Three of the 9 symptoms-nausea, dry mouth, and anorexia-were significantly reduced by OFI (all P<.05). Overall, the symptom index was reduced by 2.7 points on average (95% confidence interval, -0.2 to 5.5; P =.07), and the risk of a severe hangover (>/=18 points) was reduced by half (odds ratio, 0.38; 95% confidence interval, 0.16-0.88; P =.02). C-reactive protein levels were strongly associated with hangover severity; the mean symptom index was 4.1 (95% confidence interval, 1.2-7.1; P =.007) higher in subjects with morning C-reactive protein levels greater than 1.0 mg/L. In addition, C-reactive protein levels were 40% higher after subjects consumed placebo compared with OFI.The symptoms of the alcohol hangover are largely due to the activation of inflammation. An extract of the OFI plant has a moderate effect on reducing hangover symptoms, apparently by inhibiting the production of inflammatory mediators.

    View details for DOI 10.1001/archinte.164.12.1334

    View details for Web of Science ID 000222325400011

    View details for PubMedID 15226168

  • The relative safety of ephedra compared with other herbal products ANNALS OF INTERNAL MEDICINE Bent, S., Tiedt, T. N., Odden, M. C., Shlipak, M. G. 2003; 138 (6): 468?71

    Abstract

    Ephedra is widely used in dietary supplements that are marketed to promote weight loss or increase energy; however, the safety of this product has been questioned because of numerous case reports of adverse events.To compare the risk for adverse events attributable to ephedra and other herbal products.Comparative case series.American Association of Poison Control Centers Toxic Event Surveillance System Database Annual Report, 2001.The relative risk and 95% confidence interval for experiencing an adverse reaction after ephedra use compared with other herbs. This risk was defined as the ratio of adverse reactions to ephedra versus other products, divided by the ratio of their relative use in the United States.Products containing ephedra accounted for 64% of all adverse reactions to herbs in the United States, yet these products represented only 0.82% of herbal product sales. The relative risks for an adverse reaction in persons using ephedra compared with other herbs were extremely high, ranging from 100 (95% CI, 83 to 140) for kava to 720 (CI, 520 to 1100) for Ginkgo biloba.Ephedra use is associated with a greatly increased risk for adverse reactions compared with other herbs, and its use should be restricted.

    View details for DOI 10.7326/0003-4819-138-6-200303180-00010

    View details for Web of Science ID 000181562400004

    View details for PubMedID 12639079

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