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      Association Between Depression and Peripheral Artery Disease: Insights From the Heart and Soul Study

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          Abstract

          Background

          Depression is known to increase the risk of coronary artery disease, but few studies have evaluated the association between depression and peripheral artery disease (PAD). We examined the association of depression with PAD and evaluated potential mediators of this association.

          Methods and Results

          We used data from the Heart and Soul Study, a prospective cohort of 1024 men and women with coronary artery disease recruited in 2000–2002 and followed for a mean of 7.2±2.6 years. Depressive symptoms were assessed with the validated 9-item Patient Health Questionnaire. Prevalent PAD at baseline was determined by self-report. Prospective PAD events were adjudicated on the basis of review of medical records. We used logistic regression and Cox proportional-hazards models to estimate the independent associations of depressive symptoms with prevalent PAD and subsequent PAD events. At baseline, 199 patients (19%) had depressive symptoms (Patient Health Questionnaire ≥10). Prevalent PAD was reported by 12% of patients with depression and 7% of those without depression (base model adjusted for age and sex: odds ratio 1.79, 95% confidence interval 1.06–3.04, P=0.03; full model adjusted for comorbidities, medications, PAD risk factors, inflammation, and health behaviors: odds ratio 1.59, 95% confidence interval 0.90–2.83, P=0.11). During follow-up, PAD events occurred in 7% of patients with depression and 5% of those without depression (base model adjusted for age and sex: hazard ratio 2.09, 95% confidence interval 1.09–4.00, P=0.03; full model adjusted for comorbidities, medications, PAD risk factors, inflammation, and health behaviors: hazard ratio 1.33, 95% confidence interval 0.65–2.71, P=0.44). Factors explaining >5% of the association between depression and incident PAD events included race/ethnicity, diabetes, congestive heart failure, high-density lipoprotein, triglyceride levels, serum creatinine, inflammation, smoking, and levels of physical activity.

          Conclusions

          Depressive symptoms were associated with a greater risk of PAD. Because the association was explained partly by modifiable risk factors, our findings suggest that more aggressive treatment of these risk factors could reduce the excess risk of PAD associated with depression. ( J Am Heart Assoc. 2012;1:e002667 doi: 10.1161/JAHA.112.002667.)

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          Most cited references47

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          Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000.

          Peripheral arterial disease (PAD) is associated with significant morbidity and mortality and is an important marker of subclinical coronary heart disease. However, estimates of PAD prevalence in the general US population have varied widely. We analyzed data from 2174 participants aged 40 years and older from the 1999-2000 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index <0.90 in either leg. The prevalence of PAD among adults aged 40 years and over in the United States was 4.3% (95% CI 3.1% to 5.5%), which corresponds to approximately 5 million individuals (95% CI 4 to 7 million). Among those aged 70 years or over, the prevalence was 14.5% (95% CI 10.8% to 18.2%). In age- and gender-adjusted logistic regression analyses, black race/ethnicity (OR 2.83, 95% CI 1.48 to 5.42) current smoking (OR 4.46, 95% CI 2.25 to 8.84), diabetes (OR 2.71, 95% CI 1.03 to 7.12), hypertension (OR 1.75, 95% CI 0.97 to 3.13), hypercholesterolemia (OR 1.68, 95% CI 1.09 to 2.57), and low kidney function (OR 2.00, 95% CI 1.08 to 3.70) were positively associated with prevalent PAD. More than 95% of persons with PAD had 1 or more cardiovascular disease risk factors. Elevated fibrinogen and C-reactive protein levels were also associated with PAD. This study provides nationally representative prevalence estimates of PAD in the United States, revealing that PAD affects more than 5 million adults. PAD prevalence increases dramatically with age and disproportionately affects blacks. The vast majority of individuals with PAD have 1 or more cardiovascular disease risk factors that should be targeted for therapy.
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            Depression and poor glycemic control: a meta-analytic review of the literature.

            Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically reviewed. Our objective was to determine whether depression is associated with poor glycemic control. Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate effect sizes (ESs), and statistically analyze the collective data. A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15). Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the long-term course of diabetes.
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              The impact of confounder selection criteria on effect estimation.

              Much controversy exists regarding proper methods for the selection of variables in confounder control. Many authors condemn any use of significance testing, some encourage such testing, and other propose a mixed approach. This paper presents the results of a Monte Carlo simulation of several confounder selection criteria, including change-in-estimate and collapsibility test criteria. The methods are compared with respect to their impact on inferences regarding the study factor's effect, as measured by test size and power, bias, mean-squared error, and confidence interval coverage rates. In situations in which the best decision (of whether or not to adjust) is not always obvious, the change-in-estimate criterion tends to be superior, though significance testing methods can perform acceptably if their significance levels are set much higher than conventional levels (to values of 0.20 or more).
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                Author and article information

                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                ahaoa
                jah3
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                Blackwell Publishing Ltd
                2047-9980
                August 2012
                24 August 2012
                : 1
                : 4
                : e002667
                Affiliations
                [1 ]Department of Surgery, University of California San Francisco, San Francisco, CA (S.M.G., J.H.)
                [2 ]Department of Medicine, University of California San Francisco, San Francisco, CA (M.A.W., B.E.C.)
                [3 ]Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA (E.V., M.A.W.)
                [4 ]Department of Surgery, Veterans Affairs Medical Center, San Francisco, CA (S.M.G.)
                [5 ]Department of Medicine, Veterans Affairs Medical Center, San Francisco, CA (M.A.W., B.E.C.)
                [6 ]Saint Luke's Mid America Heart Institute, Kansas City, MO (K.G.S.)
                [7 ]Center of Research on Psychology in Somatic Diseases, Tilburg University, The Netherlands (K.G.S.)
                Author notes
                Correspondence to: S. Marlene Grenon, MDCM, MMSc, FRCSC, Department of Surgery, Division of Vascular and Endovascular Surgery, University of California San Francisco, Surgical Services, Veterans Affairs Medical Center, Mail Code 112G, 4150 Clement St, San Francisco, CA 94121. E-mail marlene.grenon@ 123456ucsfmedctr.org

                SD indicates standard deviation; PAD, peripheral artery disease; CRP, C-reactive protein; IL, interleukin.

                Article
                jah356
                10.1161/JAHA.112.002667
                3487348
                23130170
                521777c8-fc0e-4a9d-b5c6-39fb2ad3c50b
                © 2012 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley-Blackwell.

                This is an Open Access article under the terms of the Creative Commons Attribution Noncommercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 18 April 2012
                : 26 June 2012
                Categories
                Original Research
                Vascular Medicine

                Cardiovascular Medicine
                depression,peripheral artery disease,risk factors
                Cardiovascular Medicine
                depression, peripheral artery disease, risk factors

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