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The association of comorbid depression with mortality and amputation in veterans with peripheral artery disease.

ABSTRACT: 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 6 months 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, 5.9 years). 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.

SUBMITTER: Arya S

PROVIDER: S-EPMC6057818 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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The association of comorbid depression with mortality and amputation in veterans with peripheral artery disease.

Arya Shipra S Lee Sujin S Zahner Greg J GJ Cohen Beth E BE Hiramoto Jade J Wolkowitz Owen M OM Khakharia Anjali A Binney Zachary O ZO Grenon S Marlene SM

Journal of vascular surgery 20180324 2

<h4>Objective</h4>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.<h4>Methods</h4>An observational retrospective cohort of 155,647 patients with incident PAD (2003-2014) from nationwide U.S. Veterans Health Administ ...[more]

PMID: 29588133

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Project description: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 155?647 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.

Project description:ImportanceThe prevalence and morbidity of peripheral artery disease (PAD) are high, with limb outcomes including revascularization and amputation. In community-dwelling patients with PAD, the role of noninvasive evaluation for risk assessment and rates of limb outcomes have not been established to date.ObjectiveTo evaluate whether ankle-brachial indices are associated with limb outcomes in community-dwelling patients with PAD.Design, setting, and participantsA population-based, observational, test-based cohort study of patients was performed from January 1, 1998, to December 31, 2014. Data analysis was conducted from July 15 to December 15, 2017. Participants included a community-based cohort of 1413 patients with PAD from Olmsted County, Minnesota, identified by validated algorithms deployed to electronic health records. Automated algorithms identified limb outcomes used to build Cox proportional hazards regression models. Ankle-brachial indices and presence of poorly compressible arteries were electronically identified from digital data sets. Guideline-recommended management strategies within 6 months of diagnosis were also electronically retrieved, including therapy with statins, antiplatelet agents, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and smoking abstention.Main outcomes and measuresAnkle-brachial index (index ?0.9 indicates PAD; <.05, severe PAD; and ?1.40, poorly compressible arteries) and limb revascularization or amputation.ResultsOf 1413 patients, 633 (44.8%) were women; mean (SD) age was 70.8 (13.3) years. A total of 283 patients (20.0%) had severe PAD (ankle-brachial indices <0.5) and 350 (24.8%) had poorly compressible arteries (ankle-brachial indices ?1.4); 780 (55.2%) individuals with less than severe disease formed the reference group. Only 32 of 283 patients (11.3%) with severe disease and 68 of 350 patients (19.4%) with poorly compressible arteries were receiving 4 guideline-recommended management strategies. In the severe disease subgroup, the 1-year event rate for revascularization was 32.4% (90 events); in individuals with poorly compressible arteries, the 1-year amputation rate was 13.9% (47 events). In models adjusted for age, sex, and critical limb ischemia, poorly compressible arteries were associated with amputation (hazard ratio [HR], 3.12; 95% CI, 2.16-4.50; P?<?.001) but not revascularization (HR, 0.91; 95% CI, 0.69-1.20; P?=?.49). In contrast, severe disease was associated with revascularization (HR, 2.69; 95% CI, 2.15-3.37; P?<?.001) but not amputation (HR, 1.30; 95% CI, 0.82-2.07; P?=?.27).Conclusions and relevanceCommunity-dwelling patients with severe PAD or poorly compressible arteries have high rates of revascularization or limb loss, respectively. Guideline-recommended management strategies for secondary risk prevention are underused in the community.

Project description:Conflicting data exist regarding changes in amputation rates in patients with ulcers because of diabetes mellitus (DM) and peripheral artery disease (PAD). This study focuses on how population-based amputation rates are changing in the current treatment era.Using the California Office of Statewide Health Planning and Development Patient Discharge database, all patients who underwent major nontraumatic lower extremity (LE) amputation in 2005 through 2011 were identified. Age-adjusted population-based amputation risk was determined by year. Gender and age trends in amputation risk were estimated separately for diabetes-related amputations and PAD-related amputations, treating all California residents as the population at risk.From 2005 to 2011, 32,025 qualifying amputations were performed in California. Of these, 11,896 were DM-associated (n = 1,095), PAD-associated (n = 4,335), or associated with both conditions (n = 6,466). PAD-associated amputation rates and combined PAD/DM-associated amputation rates have changed little since 2009 after decreasing substantially over the prior 5 years, but DM-associated amputation rates have continuously increased since 2005. California residents older than the age of 80 years had the most dramatic decrease in PAD-associated amputation rates from 2005 to 2011 (i.e., from 317 to 175 per million Californians). Men with PAD/DM had amputation rate 1.5 times higher than those of patients with PAD alone and 5 times higher than rates of DM patients. In women the difference between patient with PAD and PAD/DM was not seen; however, these rates were 2.5 times higher than patients with DM alone.Preventable amputations associated with high-risk diseases are no longer decreasing despite continuing advances in care and education. Octogenarians with PAD represent the highest risk group for amputation, but DM-associated amputations have increased since 2005. Further research to understand treatment pathways for patient with LE wounds may shed light on pathways for amputation prevention in the future.

Dataset Information

The association of comorbid depression with mortality and amputation in veterans with peripheral artery disease.

Publications

The association of comorbid depression with mortality and amputation in veterans with peripheral artery disease.

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