Kristopher Kapphahn

All Publications

• Missing data strategies for time-varying confounders in comparative effectiveness studies of non-missing time-varying exposures and right-censored outcomes. Statistics in medicine Desai, M., Montez-Rath, M. E., Kapphahn, K., Joyce, V. R., Mathur, M. B., Garcia, A., Purington, N., Owens, D. K. 2019

  Abstract

  The treatment of missing data in comparative effectiveness studies with right-censored outcomes and time-varying covariates is challenging because of the multilevel structure of the data. In particular, the performance of an accessible method like multiple imputation (MI) under an imputation model that ignores the multilevel structure is unknown and has not been compared to complete-case (CC) and single imputation methods that are most commonly applied in this context. Through an extensive simulation study, we compared statistical properties among CC analysis, last value carried forward, mean imputation, the use of missing indicators, and MI-based approaches with and without auxiliary variables under an extended Cox model when the interest lies in characterizing relationships between non-missing time-varying exposures and right-censored outcomes. MI demonstrated favorable properties under a moderate missing-at-random condition (absolute bias <0.1) and outperformed CC and single imputation methods, even when the MI method did not account for correlated observations in the imputation model. The performance of MI decreased with increasing complexity such as when the missing data mechanism involved the exposure of interest, but was still preferred over other methods considered and performed well in the presence of strong auxiliary variables. We recommend considering MI that ignores the multilevel structure in the imputation model when data are missing in a time-varying confounder, incorporating variables associated with missingness in the MI models as well as conducting sensitivity analyses across plausible assumptions.

  View details for DOI 10.1002/sim.8174

  View details for PubMedID 31099433

• Maternal and neonatal outcomes associated with trophectoderm biopsy. Fertility and sterility Zhang, W. Y., von Versen-Höynck, F., Kapphahn, K. I., Fleischmann, R. R., Zhao, Q., Baker, V. L. 2019

  Abstract

  To assess whether pregnancies achieved with trophectoderm biopsy for preimplantation genetic testing (PGT) have different risks of adverse obstetric and neonatal outcomes compared with pregnancies achieved with IVF without biopsy.Observational cohort.University-affiliated fertility center.Pregnancies achieved via IVF with PGT (n = 177) and IVF without PGT (n = 180) that resulted in a live birth.None.Maternal outcomes including preeclampsia and placenta previa and neonatal outcomes including birth weight and birth defects.There was a statistically significant increase in the risk of preeclampsia among IVF+PGT pregnancies compared with IVF without PGT pregnancies, with an incidence of 10.5% versus 4.1% (adjusted odds ratio [aOR] = 3.02; 95% confidence interval [95% CI], 1.10, 8.29). The incidence of placenta previa was 5.8% in IVF+PGT pregnancies versus 1.4% in IVF without PGT pregnancies (aOR = 4.56; 95% CI, 0.93, 22.44). Similar incidences of gestational diabetes, preterm premature rupture of membranes, and postpartum hemorrhage were observed. IVF+PGT and IVF without PGT neonates did not have a significantly different gestational age at delivery or rate of preterm birth, low birth weight, neonatal intensive care unit admission, neonatal morbidities, or birth defects. All trends, including the significantly increased risk of preeclampsia in IVF+PGT pregnancies, persisted upon stratification of analysis to only singleton live births.To date, this is the largest and most extensively controlled study examining maternal and neonatal outcomes after trophectoderm biopsy. There was a statistically significant three-fold increase in the odds of preeclampsia associated with trophectoderm biopsy. Given the rise in PGT use, further investigation is warranted.

  View details for DOI 10.1016/j.fertnstert.2019.03.033

  View details for PubMedID 31103283

  View details for PubMedCentralID PMC6527329

• Transition From Heart Disease to Cancer as the Leading Cause of Death in the United States. Annals of internal medicine Hastings, K. G., Kapphahn, K., Boothroyd, D. B., Rehkopf, D. H., Cullen, M. R., Palaniappan, L. 2019; 171 (3): 225

  View details for DOI 10.7326/L19-0203

  View details for PubMedID 31382280

• Socioeconomic Differences in the Epidemiologic Transition From Heart Disease to Cancer as the Leading Cause of Death in the United States, 2003 to 2015: An Observational Study. Annals of internal medicine Hastings, K. G., Boothroyd, D. B., Kapphahn, K., Hu, J., Rehkopf, D. H., Cullen, M. R., Palaniappan, L. 2018

  Abstract

  Background: Recent data suggest that the United States is in the midst of an epidemiologic transition in the leading cause of death.Objective: To examine county-level sociodemographic differences in the transition from heart disease to cancer as the leading cause of death in the United States.Design: Observational study.Setting: U.S. death records, 2003 to 2015.Participants: Decedents aged 25 years or older, classified by racial/ethnic group.Measurements: All-cause, heart disease, and cancer mortality stratified by quintiles of county median household income. Age- and sex-adjusted mortality rates and average annual percentage of change were calculated.Results: Heart disease was the leading cause of death in 79% of counties in 2003 and 59% in 2015. Cancer was the leading cause of death in 21% of counties in 2003 and 41% in 2015. The shift to cancer as the leading cause of death was greatest in the highest-income counties. Overall, heart disease mortality rates decreased by 28% (30% in high-income counties vs. 22% in low-income counties) from 2003 to 2015, and cancer mortality rates decreased by 16% (18% in high-income counties vs. 11% in low-income counties). In the lowest-income counties, heart disease remained the leading cause of death among all racial/ethnic groups, and improvements were smaller for both heart disease and cancer.Limitation: Use of county median household income as a proxy for socioeconomic status.Conclusion: Data show that heart disease is more likely to be the leading cause of death in low-income counties. Low-income counties have not experienced the same decrease in mortality rates as high-income counties, which suggests a later transition to cancer as the leading cause of death in low-income counties.Primary Funding Source: National Institute on Minority Health and Health Disparities.

  View details for PubMedID 30422275

• Effects of reproductive period duration and number of pregnancies on midlife ECG indices: a secondary analysis from the Women's Health Initiative Clinical Trial BMJ OPEN Parikh, N. I., Kapphahn, K., Hedlin, H., Olgin, J. E., Allison, M. A., Magnani, J. W., Ryckman, K. R., Waring, M. E., Perez, M., Howard, B. V. 2018; 8 (8): e019129

  Abstract

  Pregnancy, menses and menopause are related to fluctuations in endogenous sex hormones in women, which cumulatively may alter cardiac electrical conduction. Therefore, we sought to study the association between number of pregnancies and reproductive period duration (RD, time from menarche to menopause) with ECG intervals in the Women's Health Initiative Clinical Trials.Secondary analysis of multicentre clinical trial.USA.ECGintervals: PR interval, P-wave duration, P-wave dispersion, QTc interval.n=40 687 women (mean age=62 years) participating in the Women's Health Initiative Clinical Trials. 82.5% were white, 9.3% black, 4% Hispanic and 2.7% Asian.In primary analysis, we employed multivariable linear regression models relating number of pregnancies and RD with millisecond changes in intervals from enrolment ECG. We studied effect modification by hormone therapy use.Among participants, 5+ live births versus 0 prior pregnancies was associated with a 1.32 ms increase in PR interval (95% CI 0.25 to 2.38), with a graded association with longer QTc interval (ms) (none (prior pregnancy, no live births)=0.66 (-0.56 to 1.88), 1=0.15 (-0.71 to 1.02), 2-4=0.25 (-0.43 to 0.94) and 5+ live births=1.15 (0.33 to 1.98), p=0.008). RD was associated with longer PR interval and maximum P-wave duration (but not P-wave dispersion) among never users of hormone therapy: (PR (ms) per additional RD year: 0.10 (0.04 to 0.16); higher P-wave duration (ms): 0.09 (0.06 to 0.12)). For every year increase in reproductive period, QTc decreased by 0.04 ms (-0.07 to -0.01).An increasing number of live births is related to increased and RD to decreased ventricular repolarisation time. Both grand multiparity and longer RD are related to increased atrial conduction time. Reproductive factors that alter midlife cardiac electrical conduction system remodelling in women may modestly influence cardiovascular disease risk in later life.NCT00000611; Post-results.

  View details for PubMedID 30121588

• Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD. Journal of the American Society of Nephrology : JASN Kurella Tamura, M., Desai, M., Kapphahn, K. I., Thomas, I., Asch, S. M., Chertow, G. M. 2018

  Abstract

  Background Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function.Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65-74, 75-84, and ≥85 years), eGFR (<6, 6-<9, 9-<12, 12-<15, and 15-<29 ml/min per 1.73 m2), and provision of dialysis, and survival.Result Over the mean±SEM follow-up of 3.4±2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65-74, 75-84, and ≥85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6-<9, <6, 9-<12, and 9-<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9-<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients.Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients.

  View details for PubMedID 29789430

• Dialysis Initiation and Mortality Among Older Veterans With Kidney Failure Treated in Medicare vs the Department of Veterans Affairs JAMA INTERNAL MEDICINE Tamura, M., Thomas, I., Montez-Rath, M. E., Kapphahn, K., Desai, M., Gale, R. C., Asch, S. M. 2018; 178 (5): 657–64

  Abstract

  The benefits of maintenance dialysis for older adults with end-stage renal disease (ESRD) are uncertain. Whether the setting of pre-ESRD nephrology care influences initiation of dialysis and mortality is not known.To compare initiation of dialysis and mortality among older veterans with incident kidney failure who received pre-ESRD nephrology care in fee-for-service Medicare vs the Department of Veterans Affairs (VA).Retrospective cohort study of patients from the US Medicare and VA health care systems evaluated 11 215 veterans aged 67 years or older with incident kidney failure between January 1, 2008, and December 31, 2011. Data analysis was performed March 15, 2016, through September 20, 2017.Pre-ESRD nephrology care in Medicare vs VA health care systems.Dialysis treatment and death within 2 years.Of the 11 215 patients included in the study, 11 085 (98.8%) were men; mean (SD) age was 79.1 (6.9) years. Within 2 years of incident kidney failure, 7071 (63.0%) of the patients started dialysis and 5280 (47.1%) died. Patients who received pre-ESRD nephrology care in Medicare were more likely to undergo dialysis compared with patients who received pre-ESRD nephrology care in VA (82% vs 53%; adjusted risk difference, 28 percentage points; 95% CI, 26-30 percentage points). Differences in dialysis initiation between Medicare and VA were more pronounced among patients aged 80 years or older and patients with dementia or metastatic cancer, and less pronounced among patients with paralysis (P < .05 for interaction). Two-year mortality was higher for patients who received pre-ESRD care in Medicare compared with VA (53% vs 44%; adjusted risk difference, 5 percentage points; 95% CI, 3-7 percentage points). The findings were similar in a propensity-matched analysis.Veterans who receive pre-ESRD nephrology care in Medicare receive dialysis more often yet are also more likely to die within 2 years compared with those in VA. The VA's integrated health care system and financing appear to favor lower-intensity treatment for kidney failure in older patients without a concomitant increase in mortality.

  View details for PubMedID 29630695

• Reproductive history and risk of type 2 diabetes mellitus in postmenopausal women: findings from the Women's Health Initiative MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LeBlanc, E. S., Kapphahn, K., Hedlin, H., Desai, M., Parikh, N. I., Liu, S., Parker, D. R., Anderson, M., Aroda, V., Sullivan, S., Woods, N. F., Waring, M. E., Lewis, C. E., Stefanick, M. 2017; 24 (1): 64-72

  Abstract

  The aim of the study was to understand the association between women's reproductive history and their risk of developing type 2 diabetes. We hypothesized that characteristics signifying lower cumulative endogenous estrogen exposure would be associated with increased risk.Prospective cohort analysis of 124,379 postmenopausal women aged 50 to 79 years from the Women's Health Initiative (WHI). We determined age of menarche and final menstrual period, and history of irregular menses from questionnaires at baseline, and calculated reproductive length from age of menarche and final menstrual period. Presence of new onset type 2 diabetes was from self-report. Using multivariable Cox proportional hazards models, we assessed associations between reproductive variables and incidence of type 2 diabetes.In age-adjusted models, women with the shortest (<30 y) reproductive periods had a 37% (95% CI, 30-45) greater risk of developing type 2 diabetes than women with medium-length reproductive periods (36-40 y). Women with the longest (45+ y) reproductive periods had a 23% (95% CI, 12-37) higher risk than women with medium-length periods. These associations were attenuated after full adjustment (HR 1.07 [1.01, 1.14] for shortest and HR 1.09 [0.99, 1.22] for longest, compared with medium duration). Those with a final menstrual period before age 45 and after age 55 had an increased risk of diabetes (HR 1.04; 95% CI, 0.99-1.09 and HR 1.08; 95% CI, 1.01-1.14, respectively) compared to those with age of final menstrual period between 46 and 55 years. Timing of menarche and cycle regularity was not associated with risk after full adjustment.Reproductive history may be associated with type 2 diabetes risk. Women with shorter and longer reproductive periods may benefit from lifestyle counseling to prevent type 2 diabetes.

  View details for DOI 10.1097/GME.0000000000000714

  View details for Web of Science ID 000391845600010

  View details for PubMedID 27465714

• Cross-national comparisons of increasing suicidal mortality rates for Koreans in the Republic of Korea and Korean Americans in the USA, 2003-2012. Epidemiology and psychiatric sciences Kung, A., Hastings, K. G., Kapphahn, K. I., Wang, E. J., Cullen, M. R., Ivey, S. L., Palaniappan, L. P., Chung, S. 2016: 1-12

  Abstract

  Korea has the highest suicide rate of developed countries, two times higher than the USA. Suicide trends among Koreans Americans living in the USA during the same period have not yet been described. We report suicide mortality rates and trends for four groups: (1) Korean Americans, (2) non-Hispanic White (NHW) Americans, (3) selected Asian American subgroups and (4) Koreans living in the Republic of Korea.We used US national (n = 18 113 585) and World Health Organization (WHO) (n = 232 919 253) mortality records for Korea from 2003 to 2012 to calculate suicide rates, all expressed per 100 000 persons. We assessed temporal trends and differences in age, gender and race/ethnicity using binomial regression.Suicide rates are highest in Koreans living in the Republic of Korea (32.4 for men and 14.8 for women). Suicide rates in Korean Americans (13.9 for men and 6.5 for women) have nearly doubled from 2003 to 2012 and exceed rates for all other Asian American subgroups (5.4-10.7 for men and 1.6-4.2 for women). Suicide rates among NHWs (21.0 for men and 5.6 for women) remain high. Among elders, suicide in Korean Americans (32.9 for men and 15.4 for women) is the highest of all examined racial/ethnic groups in the USA.Suicide in Korean Americans is higher than for other Asian Americans and follows temporal patterns more similar to Korea than the USA. Interventions to prevent suicide in Korean American populations, particularly among the elderly, are needed.

  View details for PubMedID 27830639

• Mortality outcomes for Chinese and Japanese immigrants in the USA and countries of origin (Hong Kong, Japan): a comparative analysis using national mortality records from 2003 to 2011. BMJ open Hastings, K. G., Eggleston, K., Boothroyd, D., Kapphahn, K. I., Cullen, M. R., Barry, M., Palaniappan, L. P. 2016; 6 (10)

  Abstract

  With immigration and minority populations rapidly growing in the USA, it is critical to assess how these populations fare after immigration, and in subsequent generations. Our aim is to compare death rates and cause of death across foreign-born, US-born and country of origin Chinese and Japanese populations.We analysed all-cause and cause-specific age-standardised mortality rates and trends using 2003-2011 US death record data for Chinese and Japanese decedents aged 25 or older by nativity status and sex, and used the WHO Mortality Database for Hong Kong and Japan decedents in the same years. Characteristics such as age at death, absolute number of deaths by cause and educational attainment were also reported.We examined a total of 10 458 849 deaths. All-cause mortality was highest in Hong Kong and Japan, intermediate for foreign-born, and lowest for US-born decedents. Improved mortality outcomes and higher educational attainment among foreign-born were observed compared with developed Asia counterparts. Lower rates in US-born decedents were due to decreased cancer and communicable disease mortality rates in the US heart disease mortality was either similar or slightly higher among Chinese-Americans and Japanese-Americans compared with those in developed Asia counterparts.Mortality advantages in the USA were largely due to improvements in cancer and communicable disease mortality outcomes. Mortality advantages and higher educational attainments for foreign-born populations compared with developed Asia counterparts may suggest selective migration. Findings add to our limited understanding of the racial and environmental contributions to immigrant health disparities.

  View details for DOI 10.1136/bmjopen-2016-012201

  View details for PubMedID 27793837

  View details for PubMedCentralID PMC5093623

• The Burden of Cancer in Asian Americans: A Report of National Mortality Trends by Asian Ethnicity CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Thompson, C. A., Gomez, S. L., Hastings, K. G., Kapphahn, K., Yu, P., Shariff-Marco, S., Bhatt, A. S., Wakelee, H. A., Patel, M. I., Cullen, M. R., Palaniappan, L. P. 2016; 25 (10): 1371-1382

  Abstract

  Asian Americans (AA) are the fastest growing U.S. population, and when properly distinguished by their ethnic origins, exhibit substantial heterogeneity in socioeconomic status, health behaviors, and health outcomes. Cancer is the second leading cause of death in the United States, yet trends and current patterns in the mortality burden of cancer among AA ethnic groups have not been documented.We report age-adjusted rates, standardized mortality ratios, and modeled trends in cancer-related mortality in the following AA ethnicities: Asian Indians, Chinese, Filipinos, Japanese, Koreans, and Vietnamese, from 2003 to 2011, with non-Hispanic whites (NHW) as the reference population.For most cancer sites, AAs had lower cancer mortality than NHWs; however, mortality patterns were heterogeneous across AA ethnicities. Stomach and liver cancer mortality was very high, particularly among Chinese, Koreans, and Vietnamese, for whom these two cancer types combined accounted for 15% to 25% of cancer deaths, but less than 5% of cancer deaths in NHWs. In AA women, lung cancer was a leading cause of death, but (unlike males and NHW females) rates did not decline over the study period.Ethnicity-specific analyses are critical to understanding the national burden of cancer among the heterogeneous AA population.Our findings highlight the need for disaggregated reporting of cancer statistics in AAs and warrant consideration of tailored screening programs for liver and gastric cancers. Cancer Epidemiol Biomarkers Prev; 25(10); 1371-82. ©2016 AACR.

  View details for DOI 10.1158/1055-9965.EPI-16-0167

  View details for PubMedID 27694108

• Alcohol Use and Breast Cancer Survival among Participants in the Women's Health Initiative. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Lowry, S. J., Kapphahn, K., Chlebowski, R., Li, C. I. 2016; 25 (8): 1268-1273

  Abstract

  Alcohol increases the risk of breast cancer even at moderate levels of intake. However, the relationship between alcohol consumption and mortality among breast cancer patients is less clear.This study included women from the Women's Health Initiative observational study and randomized trial diagnosed with breast cancer (n = 7,835). Cox proportional hazards regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for overall and breast cancer-specific (BCS) mortality associated with drinking alcohol before or after a breast cancer diagnosis. We also assessed whether changes in drinking habits after diagnosis are related to mortality.Women who were consuming alcohol prior to their breast cancer diagnosis had a nonstatistically significant 24% (95% CI, 0.56-1.04) reduced risk of BCS mortality and a 26% (95% CI, 0.61-0.89) reduced risk of all-cause mortality. Some variation was observed by estrogen receptor (ER) status as alcohol consumption was associated with a 49% (95% CI, 0.31-0.83) reduced risk of BCS mortality among ER(-) patients with no change in risk observed among ER(+) patients (HR = 0.97; 95% CI, 0.31-1.54), though the difference between these risks was not statistically significant (P for interaction = 0.39). Postdiagnosis alcohol consumption, and change in consumption patterns after diagnosis, did not appear to be associated with all-cause or BCS mortality.In this large study, consumption of alcohol before or after breast cancer diagnosis did not increase risks of overall or cause-specific mortality.Coupled with existing evidence, alcohol consumption is unlikely to have a substantial impact on mortality among breast cancer patients. Cancer Epidemiol Biomarkers Prev; 25(8); 1268-73. ©2016 AACR.

  View details for DOI 10.1158/1055-9965.EPI-16-0151

  View details for PubMedID 27197280

• Association of Leptin with Body Pain in Women. Journal of women's health (2002) Younger, J., Kapphahn, K., Brennan, K., Sullivan, S. D., Stefanick, M. L. 2016; 25 (7): 752-760

  Abstract

  Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia.

  View details for DOI 10.1089/jwh.2015.5509

  View details for PubMedID 27028709

  View details for PubMedCentralID PMC4939369

• Impact of residential UV exposure in childhood versus adulthood on skin cancer risk in Caucasian, postmenopausal women in the Women's Health Initiative CANCER CAUSES & CONTROL Ransohoff, K. J., Ally, M. S., Stefanick, M. L., Keiser, E., Spaunhurst, K., Kapphahn, K., Pagoto, S., Messina, C., Hedlin, H., Manson, J. E., Tang, J. Y. 2016; 27 (6): 817-823

  Abstract

  Sun exposure is a major risk factor for skin cancer; however, the relative contribution of ultraviolet (UV) exposure during childhood versus adulthood on skin cancer risk remains unclear.Our goal was to determine the impact of residential UV, measured by AVerage daily total GLObal solar radiation (AVGLO), exposure during childhood (birth, 15 years) versus adulthood (35, 50 years, and present) on incident non-melanoma skin cancer (NMSC) and malignant melanoma (MM) in postmenopausal women.Women were followed with yearly surveys throughout the duration of their participation in the Women's Health Initiative Observational study, a multicenter study from 1993 to 2005. A total of 56,557 women had data on all observations and were included in the baseline characteristics. The main exposure, residential UV (as measured by AVGLO), was measured by geographic residence during childhood and adulthood. Outcome was risk of incident NMSC and MM.Over 11.9 years (median follow-up), there were 9,195 (16.3 %) cases of NMSC and 518 (0.92 %) cases of MM. Compared with the reference group (women with low childhood and low adulthood UV), women with low childhood and high adulthood UV had a 21 % increased risk of NMSC (odds ratio 1.21, 95 % confidence interval 1.12, 1.31). Women with high childhood and high adulthood UV had a 19 % increased risk of NMSC (odds ratio 1.19, 95 % confidence interval 1.11, 1.27). Surprisingly, women with high childhood UV and low adulthood UV did not have a significant increase in NMSC risk compared with the reference group (odds ratio 1.08, 95 % confidence interval 0.91, 1.28) in multivariable models. Residential UV exposure in childhood or adulthood was not associated with increased melanoma risk.This study reveals an increase in NMSC risk associated with adulthood residential UV exposure, with no effect for childhood UV exposure.

  View details for DOI 10.1007/s10552-016-0730-9

  View details for Web of Science ID 000376619500011

  View details for PubMedID 27153844

• Relation of statin use with non-melanoma skin cancer: prospective results from the Women's Health Initiative. British journal of cancer Wang, A., Stefanick, M. L., Kapphahn, K., Hedlin, H., Desai, M., Manson, J. A., Strickler, H., Martin, L., Wactawski-Wende, J., Simon, M., Tang, J. Y. 2016; 114 (3): 314-320

  Abstract

  The relationship between statin use and non-melanoma skin cancer (NMSC) is unclear with conflicting findings in literature. Data from the Women's Health Initiative (WHI) Observational Study and WHI Clinical Trial were used to investigate the prospective relationship between statin use and NMSC in non-Hispanic white (NHW) postmenopausal women.The WHI study enrolled women aged 50-79 years at 40 US centres. Among 133 541 NHW participants, 118 357 with no cancer history at baseline and complete medication/covariate data comprised the analytic cohort. The association of statin use (baseline, overall as a time-varying variable, duration, type, potency, lipophilicity) and NMSC incidence was determined using random-effects logistic regression models.Over a mean of 10.5 years of follow-up, we identified 11 555 NMSC cases. Compared with participants with no statin use, use of any statin at baseline was associated with significantly increased NMSC incidence (adjusted odds ratio (ORadj) 1.21; 95% confidence interval (CI): 1.07-1.35)). In particular, lovastatin (OR 1.52; 95% CI: 1.08-2.16), simvastatin (OR 1.38; 95% CI: 1.12-1.69), and lipophilic statins (OR 1.39; 95% CI: 1.18-1.64) were associated with higher NMSC risk. Low and high, but not medium, potency statins were associated with higher NMSC risk. No significant effect modification of the statin-NMSC relationship was found for age, BMI, smoking, solar irradiation, vitamin D use, and skin cancer history.Use of statins, particularly lipophilic statins, was associated with increased NMSC risk in postmenopausal white women in the WHI cohort. The lack of duration-effect relationship points to possible residual confounding. Additional prospective research should further investigate this relationship.

  View details for DOI 10.1038/bjc.2015.376

  View details for PubMedID 26742009

  View details for PubMedCentralID PMC4742576

• Racial and Ethnic Variations in Lung Cancer Incidence and Mortality: Results From the Women's Health Initiative. Journal of clinical oncology Patel, M. I., Wang, A., Kapphahn, K., Desai, M., Chlebowski, R. T., Simon, M. S., Bird, C. E., Corbie-Smith, G., Gomez, S. L., Adams-Campbell, L. L., Cote, M. L., Stefanick, M. L., Wakelee, H. A. 2016; 34 (4): 360-368

  Abstract

  This study aimed to evaluate racial/ethnic differences in lung cancer incidence and mortality in the Women's Health Initiative Study, a longitudinal prospective cohort evaluation of postmenopausal women recruited from 40 clinical centers.Lung cancer diagnoses were centrally adjudicated by pathology review. Baseline survey questionnaires collected sociodemographic and health information. Logistic regression models estimated incidence and mortality odds by race/ethnicity adjusted for age, education, calcium/vitamin D, body mass index, smoking (status, age at start, duration, and pack-years), alcohol, family history, oral contraceptive, hormones, physical activity, and diet.The cohort included 129,951 women--108,487 (83%) non-Hispanic white (NHW); 10,892 (8%) non-Hispanic black (NHB); 4,882 (4%) Hispanic; 3,696 (3%) Asian/Pacific Islander (API); 534 (< 1%) American Indian/Alaskan Native; and 1,994 (1%) other. In unadjusted models, Hispanics had 66% lower odds of lung cancer compared with NHW (odds ratio [OR], 0.34; 95% CI, 0.2 to 0.5), followed by API (OR, 0.45; 95% CI, 0.27 to 0.75) and NHB (OR, 0.75; 95% CI, 0.59 to 0.95). In fully adjusted multivariable models, the decreased lung cancer risk for Hispanic compared with NHW women attenuated to the null (OR, 0.59; 95% CI, 0.35 to 0.99). In unadjusted models Hispanic and API women had decreased risk of death compared with NHW women (OR, 0.30 [95% CI, 0.15 to 0.62] and 0.34 [95% CI, 0.16 to 0.75, respectively); however, no racial/ethnic differences were found in risk of lung cancer death in fully adjusted models.Differences in lung cancer incidence and mortality are associated with sociodemographic, clinical, and behavioral factors. These findings suggest modifiable exposures and behaviors may contribute to differences in incidence of and mortality by race/ethnicity for postmenopausal women. Interventions focused on these factors may reduce racial/ethnic differences in lung cancer incidence and mortality.

  View details for DOI 10.1200/JCO.2015.63.5789

  View details for PubMedID 26700122

• Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans. EBioMedicine David, S. P., Wang, A., Kapphahn, K., Hedlin, H., Desai, M., Henderson, M., Yang, L., Walsh, K. M., Schwartz, A. G., Wiencke, J. K., Spitz, M. R., Wenzlaff, A. S., Wrensch, M. R., Eaton, C. B., Furberg, H., Mark Brown, W., Goldstein, B. A., Assimes, T., Tang, H., Kooperberg, C. L., Quesenberry, C. P., Tindle, H., Patel, M. I., Amos, C. I., Bergen, A. W., Swan, G. E., Stefanick, M. L. 2016; 4: 153-161

  Abstract

  Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene-environment interactions is not well understood.We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case-control study of African-American females and males (1078 lung cancer cases and 822 controls).Nine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10(- 5)). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = - 0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans.These results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers.

  View details for DOI 10.1016/j.ebiom.2016.01.002

  View details for PubMedID 26981579

• Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women's Health Initiative AMERICAN JOURNAL OF KIDNEY DISEASES Arce, C. M., Rhee, J. J., Cheung, K. L., Hedlin, H., Kapphahn, K., Franceschini, N., Kalil, R. S., Martin, L. W., Qi, L., Shara, N. M., Desai, M., Stefanick, M. L., Winkelmayer, W. C. 2016; 67 (2): 198-208

  Abstract

  Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women's Health Initiative.Prospective cohort study.Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n=8,921), African American (n=7,436), or Hispanic (n=3,054) were used to calculate estimated glomerular filtration rates (eGFRs).Categories of eGFR (exposure); race/ethnicity (effect modifier).The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death.We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity.During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories.Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics.In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.

  View details for DOI 10.1053/j.ajkd.2015.07.020

  View details for Web of Science ID 000368418800011

  View details for PubMedCentralID PMC4724531

• Weight loss on low-fat vs. low-carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: A randomized pilot trial OBESITY Gardner, C. D., Offringa, L. C., Hartle, J. C., Kapphahn, K., Cherin, R. 2016; 24 (1): 79-86

  View details for DOI 10.1002/oby.21331

  View details for PubMedID 26638192

• Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women's Health Initiative. American journal of kidney diseases : the official journal of the National Kidney Foundation Arce, C. M., Rhee, J. J., Cheung, K. L., Hedlin, H., Kapphahn, K., Franceschini, N., Kalil, R. S., Martin, L. W., Qi, L., Shara, N. M., Desai, M., Stefanick, M. L., Winkelmayer, W. C. 2016; 67 (2): 198–208

  Abstract

  Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women's Health Initiative.Prospective cohort study.Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n=8,921), African American (n=7,436), or Hispanic (n=3,054) were used to calculate estimated glomerular filtration rates (eGFRs).Categories of eGFR (exposure); race/ethnicity (effect modifier).The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death.We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity.During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories.Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics.In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.

  View details for PubMedID 26337132

• Leading Causes of Death among Asian American Subgroups (2003-2011) PLOS ONE Hastings, K. G., Jose, P. O., Kapphahn, K. I., Frank, A. T., Goldstein, B. A., Thompson, C. A., Eggleston, K., Cullen, M. R., Palaniappan, L. P. 2015; 10 (4)

  Abstract

  Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups.We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs.Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

  View details for DOI 10.1371/journal.pone.0124341

  View details for Web of Science ID 000353659100048

  View details for PubMedID 25915940

  View details for PubMedCentralID PMC4411112

• Cardiovascular Disease Mortality in Asian Americans JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Jose, P. O., Frank, A. T., Kapphahn, K. I., Goldstein, B. A., Eggleston, K., Hastings, K. G., Cullen, M. R., Palaniappan, L. P. 2014; 64 (23): 2486-2494

  Abstract

  Asian Americans are a rapidly growing racial/ethnic group in the United States. Our current understanding of Asian-American cardiovascular disease mortality patterns is distorted by the aggregation of distinct subgroups.The purpose of the study was to examine heart disease and stroke mortality rates in Asian-American subgroups to determine racial/ethnic differences in cardiovascular disease mortality within the United States.We examined heart disease and stroke mortality rates for the 6 largest Asian-American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) from 2003 to 2010. U.S. death records were used to identify race/ethnicity and cause of death by International Classification of Diseases-10th revision coding. Using both U.S. Census data and death record data, standardized mortality ratios (SMRs), relative SMRs (rSMRs), and proportional mortality ratios were calculated for each sex and ethnic group relative to non-Hispanic whites (NHWs).In this study, 10,442,034 death records were examined. Whereas NHW men and women had the highest overall mortality rates, Asian Indian men and women and Filipino men had greater proportionate mortality burden from ischemic heart disease. The proportionate mortality burden of hypertensive heart disease and cerebrovascular disease, especially hemorrhagic stroke, was higher in every Asian-American subgroup compared with NHWs.The heterogeneity in cardiovascular disease mortality patterns among diverse Asian-American subgroups calls attention to the need for more research to help direct more specific treatment and prevention efforts, in particular with hypertension and stroke, to reduce health disparities for this growing population.

  View details for DOI 10.1016/j.jacc.2014.08.048

  View details for Web of Science ID 000345962400007

  View details for PubMedID 25500233

  View details for PubMedCentralID PMC4274749

• Impact of San Francisco's toy ordinance on restaurants and children's food purchases, 2011-2012. Preventing chronic disease Otten, J. J., Saelens, B. E., Kapphahn, K. I., Hekler, E. B., Buman, M. P., Goldstein, B. A., Krukowski, R. A., O'Donohue, L. S., Gardner, C. D., King, A. C. 2014; 11: E122-?

  Abstract

  In 2011, San Francisco passed the first citywide ordinance to improve the nutritional standards of children's meals sold at restaurants by preventing the giving away of free toys or other incentives with meals unless nutritional criteria were met. This study examined the impact of the Healthy Food Incentives Ordinance at ordinance-affected restaurants on restaurant response (eg, toy-distribution practices, change in children's menus), and the energy and nutrient content of all orders and children's-meal-only orders purchased for children aged 0 through 12 years.Restaurant responses were examined from January 2010 through March 2012. Parent-caregiver/child dyads (n = 762) who were restaurant customers were surveyed at 2 points before and 1 seasonally matched point after ordinance enactment at Chain A and B restaurants (n = 30) in 2011 and 2012.Both restaurant chains responded to the ordinance by selling toys separately from children's meals, but neither changed their menus to meet ordinance-specified nutrition criteria. Among children for whom children's meals were purchased, significant decreases in kilocalories, sodium, and fat per order were likely due to changes in children's side dishes and beverages at Chain A.Although the changes at Chain A did not appear to be directly in response to the ordinance, the transition to a more healthful beverage and default side dish was consistent with the intent of the ordinance. Study results underscore the importance of policy wording, support the concept that more healthful defaults may be a powerful approach for improving dietary intake, and suggest that public policies may contribute to positive restaurant changes.

  View details for DOI 10.5888/pcd11.140026

  View details for PubMedID 25032837

  View details for PubMedCentralID PMC4110247

• Relation between self-recalled childhood physical activity and adult physical activity: The women's health initiative. Open journal of epidemiology Goodman, D., Park, H. L., Stefanick, M., Leblanc, E., Bea, J., Qi, L., Kapphahn, K., LaMonte, M., Manini, T., Desai, M., Anton-Culver, H. 2013; 3 (4): 224-231

  Abstract

  Evidence suggests that childhood physical activity may play a role in the etiology and prevention of adult chronic diseases. Because researchers must often depend on self-recalled physical activity data many years after the exposure, it is important to understand factors which may influence adult recall of childhood physical activity. This study evaluated the influence of adult characteristics on reported childhood physical activity and the association between adult physical activity and self-recalled childhood physical activity.48,066 post-menopausal women from the Women's Health Initiative Observational Study reported their physical activity level during ages 5 - 9, 10 - 14, and 15 - 19.In this cohort, over 65% of the population reported the same category of physical activity over the three childhood age groups. While higher levels of childhood physical activity were significantly associated with higher adult physical activity, this association varied by race/ethnicity, education, smoking, body mass index, history of diabetes or cardiovascular disease, social support and physical functional status. Women who were consistently highly active reported adult physical activity levels that were 2.82 MET-hr/week (95% C.I. = 2.43, 3.20) higher compared to women who were always physically inactive during childhood.It is important for researchers to understand the influence of adult characteristics on reported childhood physical activity.

  View details for PubMedID 26877895