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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:BackgroundSocioeconomic factors have been shown to be associated with amputation in peripheral artery disease (PAD); however, analyses have normally focused on insurance status, race, or median income. We sought to determine whether community-level socioeconomic distress was associated with major amputation and if that association differed by race.Materials and methodsCommunity-level socioeconomic distress was measured using the distressed communities index (DCI). The DCI is a zip code level compositive socioeconomic score (0-100) that accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies. A distressed community was defined as a zip code with DCI of 40 or greater. We calculated one-year risk of major amputation by DCI score for individuals with peripheral artery disease in South Carolina, 2012-2017. Treating death as competing event, we reported Fine and Gray subdistribution hazards ratios (sdHR), adjusted for patient demographic and clinical comorbidities associated with amputation. Further analyses were completed to identify potential differences in outcomes within strata of race and DCI.ResultsAmong 82,848 individuals with peripheral artery disease, the one-year incidence of amputation was 3.5% (95% CI: 3.3%, 3.6%) and was significantly greater in distressed communities than non-distressed communities (3.9%; 95% CI: 3.8%, 4.1% vs. 2.4%; 95% CI: 2.2%, 2.6%). After controlling for death and adjusting for covariates, we found an increased hazard of amputation among individuals in a distressed community (sdHR: 1.25; 95% CI: 1.14, 1.37), which persisted across racial strata. However, regardless of DCI score, Black individuals had the highest incidence of amputation.ConclusionSocioeconomic status is independently predictive of limb amputation after controlling for demographic characteristics and clinical comorbidities. Race continues to be an important risk factor, with Black individuals having higher incidence of amputation, even in non-distressed communities, than White individuals had in distressed communities.

Project description:BackgroundAmong patients with peripheral artery disease (PAD), depression is diagnosed in 17-25% and negatively impacts wound healing, quality of life, and survival. We hypothesized that depression is underdiagnosed in patients with PAD. Additionally, given the associations between depression and mortality in PAD patients, there is an increased need to investigate the strength of this relationship. The present analysis includes 2 studies to address the following aims: (1) Investigation of the prevalence of concomitant PAD and depression in a cohort from the Southeastern United States, and (2) Examination of the association between depression and all-cause mortality in a cohort of Canadian patients with PAD.MethodsSTUDY 1: From June-August 2022, the Patient Health Questionnaire Module 9 (PHQ-9) was administered to all patients seeking PAD-related care including medical, wound/podiatric, or vascular interventional/surgical treatment, in the University of North Carolina-Chapel Hill Vascular, Wound, and Podiatry clinics. The PHQ-9 assesses symptoms over 2 weeks and is scored 0-27, with higher scores indicating increasingly severe depression. Demographics, primary diagnosis, depression history, and antidepressant prescription were determined through chart review. We compared the proportion of positive depression screenings (PHQ-9 ≥ 5) to known depression. Among those treated for depression, the PHQ-9 score severity was evaluated. T-tests and χ2 tests were used to compare means and proportions. STUDY 2: From July 2015 to October 2016, the Geriatric Depression Scale Short Form was administered to adult patients with PAD undergoing revascularization. The Geriatric Depression Scale Short Form is a self-report measure of depression with a score >5 consistent with depression. The prevalence of depression was determined; primary outcome was all-cause mortality at 6 months.ResultsSTUDY 1: In 104 PAD patients (mean age 66.6 ± 11.3 years, 37% female), 37% of respondents scored ≥5 on the PHQ-9 survey, indicating at least mild depression. Only 18% of PAD patients had a history of depression, demonstrating a significant difference between the PHQ-9 findings and documented medical history. While depression was underdiagnosed in both men and women, men were more likely to have unrecognized depression (chi-squared statistic = 35.117, df = 1, P < 0.001). Among those with a history of depression, 74% had a current prescription for antidepressant medication, but 57% still had an elevated PHQ-9 score indicating possible undertreatment. STUDY 2: In 148 patients (mean age 70.3 ± 11.0 years, 39% female) the prevalence of screened depression was 28.4%, but only 3.3% had a documented history of depression suggesting significant underdiagnosis. Patients with depression were significantly more likely to die within 6 months of revascularization (9.5% vs. 0.9%; odds ratio 1.48, 95% confidence interval: 1.08 to 2.29). There was no association between depression and risk of length of stay, reintervention, or readmission.ConclusionsDepression is underdiagnosed and undertreated among patients with PAD, which has grave consequences as it is associated with 1.5 times the odds of mortality within 6 months of revascularization. There is a critical need for more robust screenings and comprehensive mental health treatment for patients with concomitant depression and PAD.

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.

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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