Shipra Arya, MD SM FACS is an Associate Professor of Surgery at the Stanford University School of Medicine and section chief of vascular surgery at VA Palo Alto Healthcare System. She has a Master?s degree in epidemiology from the Harvard School of Public Health with focus on research methodology and cardiovascular epidemiology. She completed her General Surgery Residency at Creighton University Medical Center followed by a Vascular Surgery Fellowship at University of Michigan. She recently completed an American Heart Association (AHA) grant on risk prediction of cardiovascular outcomes and limb loss in Peripheral Arterial Disease (PAD) patients. She is currently funded by the NIH/NIA GEMSSTAR grant studying the impact of frailty on quality of surgical care in PAD and aortic aneurysm patients. The accumulated evidence from her research all points to the fact that frailty is a versatile tool that can be utilized to guide surgical decision making, inform patient consent and design quality improvement initiatives at the patient and hospital level. The field of frailty research in surgical population is still relatively nascent and her current work focuses on streamlining frailty evaluation, and implementation of patient and system level interventions to improve surgical outcomes and enhance patient centered care.

Clinical Focus

  • Vascular Surgery
  • Peripheral Arterial Disease
  • Aortic Aneurysms
  • Carotid artery disease

Academic Appointments

Administrative Appointments

  • Section Chief- Vascular Surgery, VA Palo Alto Healthcare System (2018 - Present)

Professional Education

  • Board Certification: American Board of Surgery, Vascular Surgery (2014)
  • Fellowship: University of Michigan GME Training Verifications (2013) MI
  • Board Certification: American Board of Surgery, General Surgery (2012)
  • Residency: Creighton University General Surgery Residency (2011) NE
  • Medical Education: All India Institute of Medical Sciences (2005) India

Research & Scholarship

Clinical Trials

  • Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial Recruiting

    Carotid revascularization for primary prevention of stroke (CREST-2) is two independent multicenter, randomized controlled trials of carotid revascularization and intensive medical management versus medical management alone in patients with asymptomatic high-grade carotid stenosis. One trial will randomize patients in a 1:1 ratio to endarterectomy versus no endarterectomy and another will randomize patients in a 1:1 ratio to carotid stenting with embolic protection versus no stenting. Medical management will be uniform for all randomized treatment groups and will be centrally directed.

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All Publications

  • Racial and Sex Disparities in Catheter Use and Dialysis Access in the United States Medicare Population. Journal of the American Society of Nephrology : JASN Arya, S., Melanson, T. A., George, E. L., Rothenberg, K. A., Kurella Tamura, M., Patzer, R. E., Hockenberry, J. M. 2020


    Despite efforts to increase arteriovenous fistula and graft use, 80% of patients in the United States start hemodialysis on a central venous catheter (CVC).To better understand in incident hemodialysis patients how sex and race/ethnicity are associated with time on a central venous catheter and transition to an arteriovenous fistula and graft, our observational cohort study analyzed US Renal Data System data for patients with incident ESKD aged ?66 years who started hemodialysis on a CVC in July 2010 through 2013.At 1 year, 32.7% of 74,194 patients transitioned to an arteriovenous fistula, 10.8% transitioned to an arteriovenous graft, 32.1% stayed on a CVC, and 24.5% died. Women spent a significantly longer time on a CVC than men. Compared with white patients, patients who were black, Hispanic, or of another racial/ethnicity minority spent significantly more days on a CVC. In competing risk regression, women were significantly less likely than men to transition to a fistula and more likely to transition to a graft. Compared with white patients, blacks were significantly less likely to transition to a fistula but more likely to transition to a graft, Hispanics were significantly more likely to transition to a fistula, and other races/ethnicities were significantly more likely to transition to either a fistula or a graft.Female patients spend a longer time on a CVC and are less likely to transition to permanent access. Compared with white patients, minorities also spend longer time on a CVC, but are more likely to eventually transition to permanent access. Strategies to speed transition to permanent access should target groups that currently lag in this area.

    View details for DOI 10.1681/ASN.2019030274

    View details for PubMedID 31941721

  • Association of Preoperative Patient Frailty and Operative Stress With Postoperative Mortality. JAMA surgery Shinall, M. C., Arya, S., Youk, A., Varley, P., Shah, R., Massarweh, N. N., Shireman, P. K., Johanning, J. M., Brown, A. J., Christie, N. A., Crist, L., Curtin, C. M., Drolet, B. C., Dhupar, R., Griffin, J., Ibinson, J. W., Johnson, J. T., Kinney, S., LaGrange, C., Langerman, A., Loyd, G. E., Mady, L. J., Mott, M. P., Patri, M., Siebler, J. C., Stimson, C. J., Thorell, W. E., Vincent, S. A., Hall, D. E. 2019: e194620


    Importance: Patients with frailty have higher risk for postoperative mortality and complications; however, most research has focused on small groups of high-risk procedures. The associations among frailty, operative stress, and mortality are poorly understood.Objective: To assess the association between frailty and mortality at varying levels of operative stress as measured by the Operative Stress Score, a novel measure created for this study.Design, Setting, and Participants: This retrospective cohort study included veterans in the Veterans Administration Surgical Quality Improvement Program from April 1, 2010, through March 31, 2014, who underwent a noncardiac surgical procedure at Veterans Health Administration Hospitals and had information available on vital status (whether the patient was alive or deceased) at 1 year postoperatively. A Delphi consensus method was used to stratify surgical procedures into 5 categories of physiologic stress.Exposures: Frailty as measured by the Risk Analysis Index and operative stress as measured by the Operative Stress Score.Main Outcomes and Measures: Postoperative mortality at 30, 90, and 180 days.Results: Of 432?828 unique patients (401?453 males [92.8%]; mean (SD) age, 61.0 [12.9] years), 36?579 (8.5%) were frail and 9113 (2.1%) were very frail. The 30-day mortality rate among patients who were frail and underwent the lowest-stress surgical procedures (eg, cystoscopy) was 1.55% (95% CI, 1.20%-1.97%) and among patients with frailty who underwent the moderate-stress surgical procedures (eg, laparoscopic cholecystectomy) was 5.13% (95% CI, 4.79%-5.48%); these rates exceeded the 1% mortality rate often used to define high-risk surgery. Among patients who were very frail, 30-day mortality rates were higher after the lowest-stress surgical procedures (10.34%; 95% CI, 7.73%-13.48%) and after the moderate-stress surgical procedures (18.74%; 95% CI, 17.72%-19.80%). For patients who were frail and very frail, mortality continued to increase at 90 and 180 days, reaching 43.00% (95% CI, 41.69%-44.32%) for very frail patients at 180 days after moderate-stress surgical procedures.Conclusions and Relevance: We developed a novel operative stress score to quantify physiologic stress for surgical procedures. Patients who were frail and very frail had high rates of postoperative mortality across all levels of the Operative Stress Score. These findings suggest that frailty screening should be applied universally because low- and moderate-stress procedures may be high risk among patients who are frail.

    View details for DOI 10.1001/jamasurg.2019.4620

    View details for PubMedID 31721994

  • Recalibration and External Validation of the Risk Analysis Index: A Surgical Frailty Assessment Tool. Annals of surgery Arya, S., Varley, P., Youk, A., Borrebach, J. A., Perez, S., Massarweh, N. N., Johanning, J. M., Hall, D. E. 2019


    OBJECTIVE AND BACKGROUND: The Risk Analysis Index (RAI) predicts 30-, 180-, and 365-day mortality based on variables constitutive of frailty. Initially validated, in a single-center Veteran hospital, we sought to improve model performance by recalibrating the RAI in a large, veteran surgical registry, and to externally validate it in both a national surgical registry and a cohort of surgical patients for whom RAI was measured prospectively before surgery.METHODS: The RAI was recalibrated among development and confirmation samples within the Veterans Affairs Surgical Quality Improvement Program (VASQIP; 2010-2014; N = 480,731) including major, elective noncardiac surgery patients to create the revised RAI (RAI-rev), comparing discrimination and calibration. The model was tested externally in the American College of Surgeons National Surgical Quality Improvement Program dataset (NSQIP; 2005-2014; N = 1,391,785), and in a prospectively collected cohort from the Nebraska Western Iowa Health Care System VA (NWIHCS; N = 6,856).RESULTS: Recalibrating the RAI significantly improved discrimination for 30-day [c = 0.84-0.86], 180-day [c = 0.81-0.84], and 365-day mortality [c = 0.78-0.82] (P < 0.001 for all) in VASQIP. The RAI-rev also had markedly better calibration (median absolute difference between observed and predicted 180-day mortality: decreased from 8.45% to 1.23%). RAI-rev was highly predictive of 30-day mortality (c = 0.87) in external validation with excellent calibration (median absolute difference between observed and predicted 30-day mortality: 0.6%). The discrimination was highly robust in men (c = 0.85) and women (c = 0.89). Discrimination also improved in the prospectively measured cohort from NWIHCS for 180-day mortality [c = 0.77 to 0.80] (P < 0.001).CONCLUSIONS: The RAI-rev has improved discrimination and calibration as a frailty-screening tool in surgical patients. It has robust external validity in men and women across a wide range of surgical settings and available for immediate implementation for risk assessment and counseling in preoperative patients.

    View details for PubMedID 30907757

  • Variation in center-level frailty burden and the impact of frailty on long-term survival in patients undergoing elective repair for abdominal aortic aneurysms. Journal of vascular surgery George, E. L., Chen, R., Trickey, A. W., Brooke, B. S., Kraiss, L., Mell, M. W., Goodney, P. P., Johanning, J., Hockenberry, J., Arya, S. 2019


    Frailty is increasingly recognized as a key determinant in predicting postoperative outcomes. Centers that see more frail patients may not be captured in risk adjustment, potentially accounting for poorer outcomes in hospital comparisons. We aimed to (1) determine the effect of frailty on long-term mortality in patients undergoing elective abdominal aortic aneurysm (AAA) repair and (2) evaluate the variability in frailty burden among centers in the Vascular Quality Initiative (VQI) database.Patients undergoing elective open and endovascular AAA repair (2003-2017) were identified, and those with complete data on component variables of the VQI-derived Risk Analysis Index (VQI-RAI) and centers with ?10 AAA repairs were included. VQI-RAI characteristics are sex, age, body mass index, renal failure, congestive heart failure, dyspnea, preoperative ambulation, and functional status. Frailty was defined as VQI-RAI ?35 based on prior work in surgical patients using other quality improvement databases. This corresponds to the top 12% of patients at risk in the VQI. Center-level VQI-RAI differences were assessed by analysis of variance test. Relationships between frailty and survival were compared by Kaplan-Meier analysis and the log-rank test for open and endovascular procedures. Multivariable hierarchical Cox proportional hazards regression models were calculated with random intercepts for center, controlling for frailty, race, insurance, AAA diameter, procedure type, AAA case mix, and year.A total of 15,803 patients from 185 centers were included. Mean VQI-RAI scores were 27.6 (standard deviation, 5.9; range, 4-56) and varied significantly across centers (F = 2.41, P < .001). The percentage of frail patients per center ranged from 0% to 40.0%. In multivariable analysis, frailty was independently associated with long-term mortality (hazard ratio, 2.88; 95% confidence interval, 2.6-3.2) after accounting for covariates and center-level variance. Open AAA repair was not associated with long-term mortality after adjusting for frailty (hazard ratio, 0.98; 95% confidence interval, 0.86-1.13). There was a statistically significant difference in the percentage of frail patients compared with nonfrail patients who were discharged to a rehabilitation facility or nursing home after both open (40.5% vs 17.8%; P < .0001) and endovascular repair (17.7% vs 4.6%; P < .0001).There is considerable variability of preoperative frailty among VQI centers performing elective AAA repair. Adjusting for center-level variation, frailty but not procedure type had a significant association with long-term mortality; however, frailty and procedure type were both associated with nonhome discharge. Routine measurement of frailty preoperatively by centers to identify high-risk patients may help mitigate procedural and long-term outcomes and improve shared decision-making regarding AAA repair.

    View details for DOI 10.1016/j.jvs.2019.01.074

    View details for PubMedID 31147116

  • Association of Statin Dose With Amputation and Survival in Patients With Peripheral Artery Disease. Circulation Arya, S., Khakharia, A., Binney, Z. O., DeMartino, R. R., Brewster, L. P., Goodney, P. P., Wilson, P. W. 2018; 137 (14): 1435?46


    BACKGROUND: Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality.METHODS: Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003-2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate-intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score-matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding.RESULTS: In 155647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy-only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy-only users (hazard ratio, 0.67; 95% confidence interval, 0.61-0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70-0.77, respectively). Low-to-moderate-intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75- 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81-0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins (P<0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score-matched, sensitivity, and subgroup analyses.CONCLUSIONS: Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate-intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well.

    View details for DOI 10.1161/CIRCULATIONAHA.117.032361

    View details for PubMedID 29330214

  • Frailty as measured by the Risk Analysis Index is associated with long-term death after carotid endarterectomy. Journal of vascular surgery Rothenberg, K. A., George, E. L., Barreto, N., Chen, R., Samson, K., Johanning, J. M., Trickey, A. W., Arya, S. 2020


    OBJECTIVE: The role of carotid endarterectomy (CEA) continues to be debated in the age of optimal medical therapy, particularly for patients with limited life expectancy. The Risk Analysis Index (RAI) measures frailty, a syndrome of decreased physiologic reserve, which increases vulnerability to adverse outcomes. The RAI better predicts surgical complications, nonhome discharge, and death than age or comorbidities alone. We sought to measure the association of frailty, as measured by the RAI, with postoperative in-hospital stroke, long-term stroke, and long-term survival after CEA. We also sought to determine how postoperative stroke interacts with frailty to alter survival trajectory after CEA.METHODS: We queried the Vascular Quality Initiative CEA procedure and long-term data sets (2003-2017) for elective CEAs with complete RAI case information. For all analyses, the cohort was divided into asymptomatic and symptomatic carotid stenosis. Scoring was defined as not frail (RAI<30), frail (RAI 30-34), and very frail (RAI ?35). Mortality information through December 2017 was obtained from the Social Security Death Index. Multivariable models (logistic and Cox proportional hazards regressions) were used to study the association of frail and very frail patients with the outcomes of interest. In a post hoc analysis, we created Kaplan-Meier curves to analyze patient mortality after CEA as well as after postoperative stroke.RESULTS: Of the 42,869 included patients, 17,092 (39.9%) were female, and 38,395 (89.6%) were white. There were 25,673 (59.9%) patients assigned to the asymptomatic stenosis group and 17,196 (40.1%) patients in the symptomatic stenosis group. Frailty was not associated with perioperative or long-term postoperative stroke. The risk of long-term mortality was significantly higher for frail (hazard ratio, 1.9 [1.7-2.3]) and very frail (hazard ratio, 3.1 [2.6-3.7]) asymptomatic patients; symptomatic frail and very frail patients also had a two to three times increased risk of long-term mortality. Frail and very frail patients had two to three times the risk for long-term mortality compared with patients who were not frail. Postoperative stroke negatively affected the mortality trajectory for all patients in the cohort, regardless of frailty status.CONCLUSIONS: RAI score is not associated with postoperative stroke; however, frail and very frail status is associated with decreased long-term survival in an incremental fashion based on increasing RAI. RAI assessment should be considered in the preoperative decision-making for patients undergoing CEA to ensure long-term survival and optimal surgical outcomes vs medical management.

    View details for DOI 10.1016/j.jvs.2020.01.043

    View details for PubMedID 32169359

  • Clinical Utility of the Risk Analysis Index as a Prospective Frailty Screening Tool within a Multi-practice, Multi-hospital Integrated Healthcare System. Annals of surgery Varley, P. R., Borrebach, J. D., Arya, S., Massarweh, N. N., Bilderback, A. L., Wisniewski, M. K., Nelson, J. B., Johnson, J. T., Johanning, J. M., Hall, D. E. 2020


    OBJECTIVE:: The goal of this project was to first address barriers to implementation of the Risk Analysis Index (RAI) within a large, multi-hospital, integrated healthcare delivery system, and to subsequently demonstrate its utility for identifying at-risk surgical patients.BACKGROUND: Prior studies demonstrate the validity of the RAI for evaluating preoperative frailty, but they have not demonstrated the feasibility of its implementation within routine clinical practice.METHODS: Implementation of the RAI as a frailty screening instrument began as a quality improvement initiative at the University of Pittsburgh Medical Center in July 2016. RAI scores were collected within a REDCap survey instrument integrated into the outpatient electronic health record and then linked to information from additional clinical datasets. NSQIP-eligible procedures were queried within 90 days following the RAI, and the association between RAI and postoperative mortality was evaluated using logistic regression and Cox proportional hazards models. Secondary outcomes such as inpatient length of stay and readmissions were also assessed.RESULTS: RAI assessments were completed on 36,261 unique patients presenting to surgical clinics across five hospitals from July 1 to December 31, 2016, and 8,172 of these underwent NSQIP-eligible surgical procedures. The mean RAI score was 23.6 (SD 11.2), the overall 30-day and 180-day mortality after surgery was 0.7% and 2.6%, respectively, and the median time required to collect the RAI was 33 [IQR 23-53] seconds. Overall clinic compliance with the recommendation for RAI assessment increased from 58% in the first month of the study period to 84% in the sixth and final month. RAI score was significantly associated with risk of death (HR=1.099 [95% C.I.: 1.091 - 1.106], p < 0.001). At an RAI cutoff of ?37, the positive predictive values for 30- and 90-day readmission were 14.8% and 26.2%, respectively, and negative predictive values were 91.6% and 86.4%, respectively.CONCLUSIONS: The RAI frailty screening tool can be efficiently implemented within multi-specialty, multi-hospital healthcare systems. In the context of our findings and given the value of the RAI in predicting adverse postoperative outcomes, health systems should consider implementing frailty screening within surgical clinics.

    View details for DOI 10.1097/SLA.0000000000003808

    View details for PubMedID 32118596

  • Association of peripheral artery disease with life-space mobility restriction and mortality incommunity-dwelling older adults. Journal of vascular surgery Arya, S., Khakharia, A., Rothenberg, K. A., Johnson, T. M., Sawyer, P., Kennedy, R. E., Brown, C. J., Bowling, C. B. 2020


    OBJECTIVE: Symptomatic peripheral artery disease (PAD) impairs walking, but data on the impact of PAD on community mobility is limited. Life-space mobility measures the distance, frequency, and assistance needed as older adults move through geographic areas extending from their bedroom (life-space mobility score: 0) to beyond their town (life-space mobility score: 120). We evaluated the association of PAD with longitudinal life-space mobility trajectory.METHODS: Participants were part of the University of Alabama at Birmingham Study of Aging, a longitudinal study of community-dwelling older adults who were observed from 2001 to 2009. We limited our analysis to those who survived at least 6months (N= 981). PAD was based on self-report with verification by physician report and hospital records. Our primary outcome was life-space mobility score assessed every 6months. A multilevel change model (mixed model) was used to determine the association between PAD and life-space mobility trajectory during a median 7.9years of follow-up.RESULTS: Participants had a mean age of 75.7 (standard deviation, 6.7) years; 50.5% were female, and 50.4% were African American. PAD prevalence was 10.1%, and 57.1% of participants with PAD died. In participants with both PAD and life-space restriction, defined as life-space mobility score<60, we observed the highest mortality (73.1%). In a multivariable adjusted mixed effects model, participants with PAD had a more rapid decline in life-space mobility by-1.1 (95% confidence interval [CI],-1.9 to-0.24) points per year compared with those without PAD. At 5-year follow-up, model-adjusted mean life-space mobility was 48.1 (95% CI, 43.5-52.7) and 52.4 (95% CI, 50.9-53.8) among those with and without PAD, respectively, corresponding to a restriction in independent life-space mobility at the level of one's neighborhood.CONCLUSIONS: Life-space mobility is a novel patient-centered measure of community mobility, and PAD is associated with significant life-space mobility decline among community-dwelling older adults. Further study is needed to mechanistically confirm these findings and to determine whether better recognition and treatment of PAD alter the trajectory of life-space mobility.

    View details for DOI 10.1016/j.jvs.2019.08.276

    View details for PubMedID 32081483

  • Association of Sex With Repair Type and Long-term Mortality in Adults With Abdominal Aortic Aneurysm. JAMA network open Ramkumar, N., Suckow, B. D., Arya, S., Sedrakyan, A., Mackenzie, T. A., Goodney, P. P., Brown, J. R. 2020; 3 (2): e1921240


    Importance: Sex-based differences exist in the prevalence and clinical presentation of abdominal aortic aneurysm (AAA). However, it is unclear if sex is associated with AAA repair type and long-term mortality.Objective: To investigate whether a sex-related difference exists in mortality risk after AAA repair owing to differences in repair type.Design, Setting, and Participants: This cohort study uses data from the Vascular Quality Initiative, a national clinical registry, and Medicare claims to investigate endovascular and surgical repair procedures performed between January 1, 2003, and September 30, 2015, in patients aged 65 years or older with AAA. The data were analyzed from October 1, 2018, to November 19, 2019.Exposure: Sex of the patient.Main Outcomes and Measures: Endovascular (EVR) or open surgical AAA repair type and subsequent long-term, all-cause mortality.Results: In this cohort study of 16?386 patients, 12?757 (77.9%) were men and 3629 (22.1%) were women. Women were more likely than men to be older (mean [SD] age, 77 [6.5] years vs 75 [6.6] years; P<.001), active smokers (33% vs 28%; P<.001), and to have smaller aneurysms (mean [SD] diameter, 57 [11.7] mm vs 59 [17.7] mm; P<.001). Surgical AAA repair was performed in 27% (983 of 3629) of women compared with 18% (2328 of 12?757) of men (P<.001). After inverse probability weighting for risk adjustment, women were more likely to receive open surgical repair than EVR repair (risk ratio, 1.65; 95% CI, 1.51-1.80). The 10-year unadjusted survival rate after EVR repair was 14% lower in women than in men (23% vs 37%; log-rank P<.001), but the rates were comparable after open surgical repair (36% in men vs 32% in women; log-rank P=.22). Risk-adjusted analysis showed that women were associated with higher mortality rates after EVR repair (hazard ratio, 1.13; 95% CI, 1.03-1.24), whereas both men and women had a similar risk of death after open surgical repair (hazard ratio, 0.94; 95% CI, 0.84-1.06). After further stratification by symptom severity, higher risk of mortality among women was limited to elective EVR and open surgical repair for ruptured AAA.Conclusions and Relevance: In this study, women were 65% more likely than men to undergo open surgical repair. After EVR repair, women were 13% more likely to die than men, although no sex-based difference in mortality was found after open surgical repair. The differential treatment benefit of EVR repair in women is concerning given the shift toward an EVR-first approach to AAA repair.

    View details for DOI 10.1001/jamanetworkopen.2019.21240

    View details for PubMedID 32058556

  • Practical Guide to Meta-analysis. JAMA surgery Arya, S., Schwartz, T. A., Ghaferi, A. A. 2020

    View details for DOI 10.1001/jamasurg.2019.4523

    View details for PubMedID 31995161

  • Assessment of Risk Analysis Index for Prediction of Mortality, Major Complications and Length of Stay in Vascular Surgery Patients. Annals of vascular surgery Rothenberg, K. A., George, E. L., Trickey, A. W., Barreto, N. B., Johnson, T. M., Hall, D. E., Johanning, J. M., Arya, S. 2020


    INTRODUCTION: Frailty is a risk factor for adverse postoperative outcomes. We aimed to test the performance of a prospectively-validated frailty measure, the Risk Analysis Index (RAI) in vascular surgery patients and delineate the additive impact of procedure complexity on surgical outcomes.METHODS: We queried the 2007-2013 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to identify six major elective vascular procedure categories (carotid revascularization, abdominal aortic aneurysm [AAA] repair, suprainguinal revascularization, infrainguinal revascularization, thoracic aortic aneurysm [TAA] repair, and thoracoabdominal aortic aneurysm [TAAA] repair). We trained and tested logistic regression models for 30-day mortality, major complications and prolonged length of stay (LOS). The first model, "RAI", used the RAI alone; "RAI-Procedure (RAI-P)" included procedure category (e.g., AAA repair) and procedure approach (e.g., endovascular); "RAI-Procedure Complexity (RAI-PC)" added outpatient versus inpatient surgery, general anesthesia use, work relative value units (RVUs), and operative time.RESULTS: The RAI model was a good predictor of mortality for vascular procedures overall (C-statistic 0.72). The C-statistic increased with the RAI-P (0.78), which further improved minimally, with the RAI-PC (0.79). When stratified by procedure category, the RAI predicted mortality well for infrainguinal (0.79) and suprainguinal (0.74) procedures, moderately well for AAA repairs (0.69) and carotid revascularizations (0.70), and poorly for TAAs (0.62) and TAAAs (0.54). For carotid, infrainguinal, and suprainguinal procedures, procedure complexity (RAI-PC) had little impact on model discrimination for mortality, did improve discrimination for AAAs (0.84), TAAs (0.73), and TAAAs (0.80). While the RAI model was not a good predictor for major complications or LOS, discrimination improved for both with the RAI-PC model.CONCLUSIONS: Frailty as measured by the RAI was a good predictor of mortality overall after vascular surgery procedures. While the RAI was not a strong predictor of major complications or prolonged LOS, the models improved with the addition of procedure characteristics like procedure category and approach.

    View details for DOI 10.1016/j.avsg.2020.01.015

    View details for PubMedID 31935435

  • Validation of the Risk Analysis Index for Evaluating Frailty in Ambulatory Patients. Journal of the American Geriatrics Society Shah, R., Borrebach, J. D., Hodges, J. C., Varley, P. R., Wisniewski, M. K., Shinall, M. C., Arya, S., Johnson, J., Nelson, J. B., Youk, A., Massarweh, N. N., Johanning, J. M., Hall, D. E. 2020


    Frailty is a marker of dependency, disability, hospitalization, and mortality in community-dwelling older adults. However, existing tools for measuring frailty are too cumbersome for rapid point-of-care assessment. The Risk Analysis Index (RAI) of frailty is validated in surgical populations, but its performance outside surgical populations is unknown.Validate the RAI in ambulatory patients.Observational cohort study of outpatient surgical clinics within the University of Pittsburgh Medical Center Healthcare System between July 1, 2016, and December 31, 2016. Frailty was assessed using the RAI. Current Procedural Terminology codes following RAI assessment identified patients with and without minor office-based procedures (eg, joint injection, laryngoscopy).All-cause 1-year mortality, assessed by stratified Cox proportional hazard models.Of 28,059 patients, 13,861 were matched to a minor, office-based procedure and 14,198 did not undergo any procedure. The mean (SD) age was 56.7 (17.2) years; women constituted 15,797 (56.3%) of the cohort. Median time (interquartile range 25th-75th percentile) to measure RAI was 30 (22-47) seconds. Mortality among the frail was two to five times that of patients with normal RAI scores. For example, the hazard ratio for frail ambulatory patients without a minor procedure was 3.69 (95% confidence interval [CI] =?2.51-5.41), corresponding to 30-, 180-, and 365-day mortality rates of 2.9%, 11.2%, and 17.4%, respectively, compared to 0.3%, 2.3%, and 4.0% among patients with normal RAI scores. Discrimination of mortality (overall, and censored at 30, 180, and 365?days) was excellent, ranging from c = 0.838 (95% CI = 0.773-0.902) for 30-day mortality after minor procedures to c = 0.909 (95% CI = 0.855-0.964) without a procedure.RAI is a valid, easily administered tool for point-of-care frailty assessment in ambulatory populations that may help clinicians and patients make better informed decisions about care choices-especially among patients considered high risk with a potentially limited life span.

    View details for DOI 10.1111/jgs.16453

    View details for PubMedID 32310317

  • Poor glycemic control is associated with significant increase in major limb amputation and adverse events in the 30-day postoperative period after infrainguinal bypass. Journal of vascular surgery McGinigle, K. L., Kindell, D. G., Strassle, P. D., Crowner, J. R., Pascarella, L., Farber, M. A., Marston, W. A., Arya, S., Kalbaugh, C. A. 2020


    Understanding modifiable risk factors to improve surgical outcomes is increasingly important in value-based health care. There is an established association between peripheral artery disease (PAD), diabetes, and limb loss, but less is known about expected outcomes after revascularization relative to the degree of glycemic control. The purpose of this study was to determine the association between hemoglobin A1c (HbA1c) management in diabetics and surgical outcomes after open infrainguinal bypass.The Vascular Quality Initiative infrainguinal bypass module was used to identify adult patients (?18 years) with a history of diabetes who underwent bypass for PAD between 2011 and 2018. Exclusion criteria included missing or illogical HbA1c values and if the indication for the limb treated was not PAD. Patients were categorized by preoperative HbA1c levels as low severity/controlled (<7.0%), high severity (7.0%-10.0%), and very high severity (>10.0%). Primary outcomes were 30-day incidence of major adverse cardiac events (MACEs), major adverse limb events (MALEs), ipsilateral amputation, and 1-year all-cause mortality. Thirty-day outcomes were calculated using multivariable regression to compute odds ratios; hazard ratios were calculated for all-cause mortality. All analyses were adjusted for demographics, comorbidities, and clinical characteristics.The final sample included 30,813 operations (27,988 unique patients): 17,517 (57%) nondiabetic patients, 5194 patients with low-severity/controlled diabetes, and 8102 (26%) patients with poorly controlled diabetes, including 5531 (70%) treated with insulin. There were 6439 (21%) patients with high-severity HbA1c values and 1663 (5%) patients with very-high-severity HbA1c values. Those with a very high HbA1c level were more likely to be nonwhite, insulin dependent, and active smokers. Compared with nondiabetics, patients with very-high-severity HbA1c had an 81% increase in MACEs and 31% increase in MALEs, whereas patients with high-severity HbA1c only had a 49% increase in MACEs and a 12% increase in MALEs. Each one-step increase in severity category (eg, low to high to very high) was associated with an average 29% increase in the odds of MACEs and an 8% increase in the odds of MALEs.Uncontrolled diabetes with an HbA1c value >10.0% was associated with significantly worse 30-day surgical outcomes. Patients with incrementally better glycemic control (HbA1c level of 7.0%-10.0%) did not suffer the same rate of complications, suggesting that preoperative attempts at improving diabetes management even slightly could lead to improved surgical outcomes in open infrainguinal bypass patients.

    View details for DOI 10.1016/j.jvs.2019.11.048

    View details for PubMedID 32139308

  • Association of comorbid depression with inpatient outcomes in critical limb ischemia. Vascular medicine (London, England) Zahner, G. J., Cortez, A., Duralde, E., Ramirez, J. L., Wang, S., Hiramoto, J., Cohen, B. E., Wolkowitz, O. M., Arya, S., Hills, N. K., Grenon, S. M. 2019: 1358863X19880277


    There is a growing body of evidence that peripheral artery disease (PAD) may be impacted by depression. The objective of this study is to determine whether outcomes, primarily major amputation, differ between patients with depression and those without who presented to hospitals with critical limb ischemia (CLI), the end-stage of PAD. A retrospective cohort of patients hospitalized for CLI during 2012 and 2013 was identified from the National Inpatient Sample (NIS) using ICD-9 codes. The primary outcome was major amputation and secondary outcomes were length of stay and other complications. The sample included 116,008 patients hospitalized for CLI, of whom 10,512 (9.1%) had comorbid depression. Patients with depression were younger (64 ± 14 vs 67 ± 14 years, p < 0.001) and more likely to be female (55% vs 41%, p < 0.001), white (73% vs 66%, p < 0.001), and tobacco users (46% vs 41%, p < 0.001). They were also more likely to have prior amputations (9.8% vs 7.9%, p < 0.001). During the hospitalization, the rate of major amputation was higher in patients with comorbid depression (11.5% vs 9.1%, p < 0.001). In multivariable analysis, excluding patients who died prior to/without receiving an amputation (n = 2621), comorbid depression was associated with a 39% increased odds of major amputation (adjusted OR 1.39, 95% CI 1.30, 1.49; p < 0.001). Across the entire sample, comorbid depression was also independently associated with a slightly longer length of stay (beta = 0.199, 95% CI 0.155, 0.244; p < 0.001). These results provide further evidence that depression is a variable of interest in PAD and surgical quality databases should include mental health variables to enable further study.

    View details for DOI 10.1177/1358863X19880277

    View details for PubMedID 31713461

  • Simplifying Hospital Quality Comparisons for Vascular Surgery Using Center-Level Frailty Burden Rather than Comorbidities George, E. L., Rothenberg, K., Barreto, N. L., Chen, R., Trickey, A. W., Arya, S. ELSEVIER SCIENCE INC. 2019: S163?S164
  • Novel Preoperative Risk Score to Identify Patients at High Risk for Non-Home Discharge after Elective Thoracic Endovascular Aortic Aneurysm Repair Ramirez, J. L., Zarkowsky, D. S., Boitano, L. T., Conrad, M. F., Arya, S., Gasper, W. J., Conte, M. S., Iannuzzi, J. C. ELSEVIER SCIENCE INC. 2019: S332
  • Patients with Depression Are Less Likely to Go Home after Critical Limb Revascularization Ramirez, J. L., Zahner, G. J., Arya, S., Grenon, S., Gasper, W. J., Sosa, J. A., Conte, M. S., Iannuzzi, J. C. ELSEVIER SCIENCE INC. 2019: S332?S333
  • Genome-wide association study of peripheral artery disease in the Million Veteran Program. Nature medicine Klarin, D., Lynch, J., Aragam, K., Chaffin, M., Assimes, T. L., Huang, J., Lee, K. M., Shao, Q., Huffman, J. E., Natarajan, P., Arya, S., Small, A., Sun, Y. V., Vujkovic, M., Freiberg, M. S., Wang, L., Chen, J., Saleheen, D., Lee, J. S., Miller, D. R., Reaven, P., Alba, P. R., Patterson, O. V., DuVall, S. L., Boden, W. E., Beckman, J. A., Gaziano, J. M., Concato, J., Rader, D. J., Cho, K., Chang, K., Wilson, P. W., O'Donnell, C. J., Kathiresan, S., VA Million Veteran Program, Tsao, P. S., Damrauer, S. M. 2019


    Peripheral artery disease (PAD) is a leading cause of cardiovascular morbidity and mortality; however, the extent to which genetic factors increase risk for PAD is largely unknown. Using electronic health record data, we performed a genome-wide association study in the Million Veteran Program testing ~32 million DNA sequence variants with PAD (31,307 cases and 211,753 controls) across veterans of European, African and Hispanic ancestry. The results were replicated in an independent sample of 5,117 PAD cases and 389,291 controls from the UK Biobank. We identified 19 PAD loci, 18 of which have not been previously reported. Eleven of the 19 loci were associated with disease in three vascular beds (coronary, cerebral, peripheral), including LDLR, LPL and LPA, suggesting that therapeutic modulation of low-density lipoprotein cholesterol, the lipoprotein lipase pathway or circulating lipoprotein(a) may be efficacious for multiple atherosclerotic disease phenotypes. Conversely, four of the variants appeared to be specific for PAD, including F5 p.R506Q, highlighting the pathogenic role of thrombosis in the peripheral vascular bed and providing genetic support for Factor Xa inhibition as a therapeutic strategy for PAD. Our results highlight mechanistic similarities and differences among coronary, cerebral and peripheral atherosclerosis and provide therapeutic insights.

    View details for DOI 10.1038/s41591-019-0492-5

    View details for PubMedID 31285632

  • Frailty as Measured by the Risk Analysis Index Predicts Long-Term Death After Carotid Endarterectomy Rothenberg, K. A., George, E., Barreto, N., Chen, R., Samson, K. K., Johanning, J. M., Trickey, A., Arya, S. MOSBY-ELSEVIER. 2019: E62
  • The Impact of Frailty on Failure to Rescue Following Elective Abdominal Aortic Aneurysm Repair George, E. L., Rothenberg, K. A., Barreto, N., Chen, R., Trickey, A., Johanning, J., Hockenberry, J., Arya, S. MOSBY-ELSEVIER. 2019: E124?E125
  • Association of Frailty and Postoperative Complications With Unplanned Readmissions After Elective Outpatient Surgery. JAMA network open Rothenberg, K. A., Stern, J. R., George, E. L., Trickey, A. W., Morris, A. M., Hall, D. E., Johanning, J. M., Hawn, M. T., Arya, S. 2019; 2 (5): e194330


    Importance: Ambulatory surgery in geriatric populations is increasingly prevalent. Prior studies have demonstrated the association between frailty and readmissions in the inpatient setting. However, few data exist regarding the association between frailty and readmissions after outpatient procedures.Objective: To examine the association between frailty and 30-day unplanned readmissions after elective outpatient surgical procedures as well as the potential mediation of surgical complications.Design, Setting, and Participants: In this retrospective cohort study of elective outpatient procedures from 2012 and 2013 in the National Surgical Quality Improvement Program (NSQIP) database, 417?840 patients who underwent elective outpatient procedures were stratified into cohorts of individuals with a length of stay (LOS) of 0 days (LOS=0) and those with a LOS of 1 or more days (LOS?1). Statistical analysis was performed from June 1, 2018, to March 31, 2019.Exposure: Frailty, as measured by the Risk Analysis Index.Main Outcomes and Measures: The main outcome was 30-day unplanned readmission.Results: Of the 417?840 patients in this study, 59.2% were women and unplanned readmission occurred in 2.3% of the cohort overall (LOS=0, 2.0%; LOS?1, 3.4%). Frail patients (mean [SD] age, 64.9 [15.5] years) were more likely than nonfrail patients (mean [SD] age, 35.0 [15.8] years) to have an unplanned readmission in both LOS cohorts (LOS=0, 8.3% vs 1.9%; LOS?1, 8.5% vs 3.2%; P<.001). Frail patients were also more likely than nonfrail patients to experience complications in both cohorts (LOS=0, 6.9% vs 2.5%; LOS?1, 9.8% vs 4.6%; P<.001). In multivariate analysis, frailty doubled the risk of unplanned readmission (LOS=0: adjusted relative risk [RR], 2.1; 95% CI, 2.0-2.3; LOS?1: adjusted RR, 1.8; 95% CI, 1.6-2.1). Complications occurred in 3.1% of the entire cohort, and frailty was associated with increased risk of complications (unadjusted RR, 2.6; 95% CI, 2.4-2.8). Mediation analysis confirmed that complications are a significant mediator in the association between frailty and readmissions; however, it also indicated that the association of frailty with readmission was only partially mediated by complications (LOS=0, 22.8%; LOS?1, 29.3%).Conclusions and Relevance: These findings suggest that frailty is a significant risk factor for unplanned readmission after elective outpatient surgery both independently and when partially mediated through increased complications. Screening for frailty might inform the development of interventions to decrease unplanned readmissions, including those for outpatient procedures.

    View details for DOI 10.1001/jamanetworkopen.2019.4330

    View details for PubMedID 31125103

  • The Importance of Incorporating Frailty Screening Into Surgical Clinical Workflow JAMA NETWORK OPEN George, E. L., Arya, S. 2019; 2 (5)
  • Appropriateness of Carotid Endarterectomy in Asymptomatic Carotid Disease-Predicting 5-Year Survival JAMA SURGERY Rothenberg, K. A., Arya, S. 2019; 154 (4): 345
  • Outcomes and Durability of Endovascular Aneurysm Repair in Octogenarians Lagergren, E., Chihade, D., Zhan, H., Perez, S., Brewster, L., Arya, S., Jordan, W. D., Duwayri, Y. ELSEVIER SCIENCE INC. 2019: 33?39


    Endovascular aneurysm repair (EVAR) accounts for the majority of all abdominal aortic aneurysm (AAA) repairs in the United States. EVAR utilization in the aging population is increasing due to the minimally invasive nature of the procedure, the low associated perioperative morbidity, and early survival benefit over open repair. The objective of this study is to compare the outcomes of octogenarians after elective EVAR to their younger counterparts, a question that can be answered by a long-term, institutional data set.This was a retrospective series of 255 patients, who underwent elective EVAR within our institution from 2008 to 2015. A comparative analysis of patients aged 80 years and older and less than 80 years was performed. Outcomes measured included perioperative death and myocardial infarction (MI), length of stay, and readmission within 30 days. Aneurysm reintervention, long-term surveillance imaging, and aneurysm-related deaths were also evaluated. In addition, subset analyses of octogenarians were compared for survival at 24 months.Overall, 255 patients were included in our analysis. Fifty-nine patients were octogenarians, and 196 patients were nonoctogenarians. The mean age difference between the two groups was significant (84.5 years [SD, ±3.44] vs. 69.6 years [SD, ±6.13] in the ?80 and <80 groups, respectively; P < 0.0001). There was no significant difference in the mean aneurysm size (6.03 cm [SD, ±1.12] vs. 5.535 cm [SD, ±0.9]; P < 0.06) between the ?80 and < 80 groups. Octogenarians had higher rates of perioperative MI (5% vs. 1%, P < 0.04), thirty-day mortality (7% vs. 0%, P < 0.003), a higher number of perioperative complications (0.64 incidence per patient [SD, ±1.11] vs. 0.31 [SD, ±0.69], P < 0.005), and a longer mean hospital stay (5.34 [SD, ±5.75] days vs. 3.16 [SD, ±3.23] days, P < 0.0003), and they were also less likely to be discharged home after surgery (75% vs. 91%, P < 0.002). In the evaluated long-term outcomes, the two groups were similar with regard to aneurysm reintervention (10% vs. 9%, P < 0.06) and the stability of aneurysm sac size on imaging at last follow-up (71% vs. 80%, P < 0.27). The overall aortic related cause of death was different between the groups (8% vs. 1%, P < 0.003); however, the long-term aortic related mortality was not different between the two groups (2% vs. 1%, P < 0.4). Finally, a subset analysis of the octogenarian group was performed comparing patients based on survival status at 24 months. Higher preoperative creatinine (1.73 mg/dL [SD, ±1.54] vs. 1.15 mg/dL [SD, ±0.46]) and lower preoperative hematocrit (33.9% [SD, ±3.43] vs. 37.2% [SD, ±4.9]) along with number of perioperative complications (1.2 incidence per patient [SD, ±1.74] vs. 0.45 [SD, ±0.73]) were associated with death at 24 months after the index operation.Elective endovascular repair of AAA in octogenarians carries a higher risk of perioperative mortality but acceptable long-term outcomes. Appropriateness of elective EVAR in octogenarians should be answered based on this potential short-lived survival benefit, taking into account that advanced age should not be the sole basis of exclusion for otherwise suitable candidates for elective EVAR.

    View details for PubMedID 30244017

  • The Importance of Incorporating Frailty Screening Into Surgical Clinical Workflow. JAMA network open George, E. L., Arya, S. 2019; 2 (5): e193538

    View details for PubMedID 31074807

  • Comparison of Surgeon Assessment to Frailty Measurement in Abdominal Aortic Aneurysm Repair. The Journal of surgical research George, E. L., Kashikar, A., Rothenberg, K. A., Barreto, N. L., Chen, R., Trickey, A. W., Arya, S. 2019; 248: 38?44


    Endovascular abdominal aortic aneurysm repair (EVAR) allows us to intervene on patients otherwise considered poor candidates for open repair. Despite its importance in determining operative approach, no comparison has been made between the subjective "eyeball test" and an objective measurement of preoperative frailty for EVAR patients.Patients undergoing elective EVAR were identified in the Vascular Quality Initiative (VQI) database (2003-2017). Patients were classified "unfit" based on a surgeon-reported variable. Frailty was defined using the VQI-derived Risk Analysis Index, which includes sex, age, BMI, renal failure, congestive heart failure, dyspnea, preoperative ambulation, and functional status. The association between fitness and/or frailty and adverse outcomes was determined by logistic regression.A total of 11,694 patients undergoing elective EVAR were included of which only 18.1% were "unfit," whereas 34.6% were "frail" and overall 43.6% "unfit or frail." Patients deemed "unfit" or "frail" had significantly increased odds of mortality, complications, and nonhome discharge (P < 0.001), and both frailty and unfitness generated negative predictive values for these outcomes greater than 93%. In adjusted logistic regression, the addition of objective frailty significantly improved model performance in predicting nonhome discharge (C-statistic 0.65 versus 0.71, P < 0.001) and complications (0.59 versus 0.61, P = 0.01), but similarly predicted mortality (0.74 versus 0.73, P = 0.99).Preoperative frailty assessment provides a useful objective measure of risk stratification as an adjunct to a physician's clinical intuition. The addition of frailty expands the pool of high-risk patients who are more likely to experience adverse postoperative events after elective EVAR and may benefit from uniquely tailored perioperative interventions.

    View details for DOI 10.1016/j.jss.2019.11.005

    View details for PubMedID 31841735

  • Appropriateness of Carotid Endarterectomy in Asymptomatic Carotid Disease-Predicting 5-Year Survival. JAMA surgery Rothenberg, K. A., Arya, S. 2019

    View details for PubMedID 30624550

  • Poor glycemic control is a strong predictor of postoperative morbidity and mortality in patients undergoing vascular surgery. Journal of vascular surgery Long, C. A., Fang, Z. B., Hu, F. Y., Arya, S., Brewster, L. P., Duggan, E., Duwayri, Y. 2018


    OBJECTIVE: Hyperglycemia is a common occurrence in patients undergoing cardiovascular surgery. It has been identified in several surgical cohorts that improved perioperative glycemic control reduced postoperative morbidity and mortality. A significant portion of the population with peripheral arterial disease suffers from the sequelae of diabetes or metabolic syndrome. A paucity of data exists regarding the relationship between perioperative glycemic control and postoperative outcomes in vascular surgery patients. The objective of this study was to better understand this relationship and to determine which negative perioperative outcomes could be abated with improved glycemic control.METHODS: This is a retrospective review of a vascular patient database at a large academic center from 2009 to 2013. Eligible procedures included carotid endarterectomy and stenting, endovascular and open aortic aneurysm repair, and all open bypass revascularization procedures. Data collected included standard demographics, outcome parameters, and glucose levels in the perioperative period. Perioperative hyperglycemia was defined as at least one glucose value>180mg/dL within 72hours of surgery. The primary outcome was 30-day mortality, with secondary outcomes of complications, need to return to the operating room, and readmission.RESULTS: Of the total 1051 patients reviewed, 366 (34.8%) were found to have perioperative hyperglycemia. Hyperglycemic patients had a higher 30-day mortality (5.7% vs 0.7%; P< .01) and increased rates of acute renal failure (4.9% vs 0.9%; P<.01), postoperative stroke (3.0% vs 0.7%; P< .01), and surgical site infections (5.7% vs 2.6%; P= .01). In addition, these patients were also more likely to undergo readmission (12.3% vs 7.9%; P= .02) and reoperation (6.3% vs 1.8%; P< .01). Furthermore, multivariable logistic regression demonstrated that perioperative hyperglycemia had a strong association with increased 30-day mortality and multiple negative postoperative outcomes, including myocardial infarction, stroke, renal failure, and wound complications.CONCLUSIONS: This study demonstrates a strong association between perioperative glucose control and 30-day mortality in addition to multiple other postoperative outcomes after vascular surgery.

    View details for PubMedID 30459015

  • Long-Term Mortality in Carotid Revascularization Patients Procedure Risk Versus Patient Risk? CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Arya, S., Girotra, S. 2018; 11 (11)
  • Interaction of Frailty and Postoperative Complications on Unplanned Readmission after Elective Outpatient Surgery Stern, J. R., Blum, K., Trickey, A. W., Hall, D. E., Johanning, J. M., Morris, A. M., Hawn, M. T., Arya, S. ELSEVIER SCIENCE INC. 2018: E25
  • Evaluation of Peripheral Calcium Score as a Measure of Peripheral Artery Disease Severity Lee, S., Kalra, K., Path, B., Little, B., Bernheim, A., Brewster, L., Shaw, L., Arya, S. MOSBY-ELSEVIER. 2018: E137
  • The association of comorbid depression with mortality and amputation in veterans with peripheral artery disease. Journal of vascular surgery Arya, S., Lee, S., Zahner, G. J., Cohen, B. E., Hiramoto, J., Wolkowitz, O. M., Khakharia, A., Binney, Z. O., Grenon, S. M. 2018


    OBJECTIVE: Peripheral artery disease (PAD) is an increasing health concern with rising incidence globally. Previous studies have shown an association between PAD incidence and depression. The objective of the study was to determine the association of comorbid depression with PAD outcomes (amputation and all-cause mortality rates) in veterans.METHODS: An observational retrospective cohort of 155,647 patients with incident PAD (2003-2014) from nationwide U.S. Veterans Health Administration hospitals was conducted using the national Veterans Affairs Corporate Data Warehouse. Depression was measured using concurrent International Classification of Diseases, Ninth Revision diagnosis codes 6months before or after PAD diagnosis. The main outcomes were incident major amputation and all-cause mortality. Crude associations were assessed with Kaplan-Meier plots. The effects of depression adjusted for covariates were analyzed using Cox proportional hazards models.RESULTS: Depression was present in 16% of the cohort, with the occurrence of 9517 amputations and 63,287 deaths (median follow-up, 5.9years). Unadjusted hazard ratios (HRs) of comorbid depression for amputations and all-cause mortality were 1.32 (95% confidence interval [CI], 1.25-1.39) and 1.02 (95% CI, 0.99-1.04), respectively. After adjustment for covariates in Cox regression models, a diagnosis of comorbid depression at the time of PAD diagnosis was associated with a 13% higher amputation (HR, 1.13; 95% CI, 1.07-1.19) and 17% higher mortality (HR, 1.17; 95% CI, 1.14-1.20) risk compared with patients with no depression. On stratification by use of antidepressants, depressed patients not taking antidepressants had a 42% higher risk of amputation (HR, 1.42; 95% CI, 1.27-1.58) compared with those without depression. Patients taking antidepressants for depression still had increased risk of amputation but only 10% higher compared with those without depression (HR, 1.10; 95% CI, 1.03-1.17). Interestingly, patients taking antidepressants for other indications also had a higher risk of amputation compared with those not having depression or not taking antidepressants (HR, 1.08; 95% CI, 1.03-1.14). Having any diagnosis of depression or the need for antidepressants increased the mortality risk by 18% to 25% in the PAD cohort compared with those without depression and not taking antidepressants for any other indication.CONCLUSIONS: PAD patients with comorbid depression have a significantly higher risk of amputation and mortality than PAD patients without depression. Furthermore, untreated depression was associated with an increased amputation risk in the PAD population, more so than depression or other mental illness being treated by antidepressants. The underlying mechanisms for causality, if any, remain to be determined. The association of antidepressant treatment use with amputation risk should prompt further investigations into possible mechanistic links between untreated depression and vascular dysfunction.

    View details for PubMedID 29588133

  • Race and Socioeconomic Status Independently Affect Risk of Major Amputation in Peripheral Artery Disease. Journal of the American Heart Association Arya, S., Binney, Z., Khakharia, A., Brewster, L. P., Goodney, P., Patzer, R., Hockenberry, J., Wilson, P. W. 2018; 7 (2)


    BACKGROUND: Black race has been shown to be a risk factor for amputation in peripheral artery disease (PAD); however, race has been argued to be a marker for socioeconomic status (SES) rather than true disparity. The aim of this study is to study the impact of race and SES on amputation risk in PAD patients.METHODS AND RESULTS: Patients with incident PAD in the national Veterans Affairs Corporate Data Warehouse were identified from 2003 to 2014 (N=155647). The exposures were race and SES (measured by median income in residential ZIP codes). The outcome was incident major amputation. Black veterans were significantly more likely to live in low-SES neighborhoods and to present with advanced PAD. Black patients had a higher amputation risk in each SES stratum compared with white patients. In Cox models (adjusting for covariates), black race was associated with a 37% higher amputation risk compared with white race (hazard ratio: 1.37; 95% confidence interval, 1.30-1.45), whereas low SES was independently predictive of increased risk of amputation (hazard ratio: 1.12; 95% confidence interval, 1.06-1.17) and showed no evidence of interaction with race. In predicted amputation risk analysis, black race and low SES continued to be significant risk factors for amputation regardless of PAD presentation.CONCLUSIONS: Black race significantly increases the risk of amputation within the same SES stratum compared with white race and has an independent effect on limb loss after controlling for comorbidities, severity of PAD at presentation, and use of medications.

    View details for PubMedID 29330260

  • Long-Term Mortality in Carotid Revascularization Patients. Circulation. Cardiovascular quality and outcomes Arya, S., Girotra, S. 2018; 11 (11): e004875

    View details for PubMedID 30571342

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