Elsevier

Clinical Therapeutics

Volume 36, Issue 11, 1 November 2014, Pages 1518-1530
Clinical Therapeutics

Original Research
Depression, Coronary Artery Disease, and Physical Activity: How Much Exercise Is Enough?

https://doi.org/10.1016/j.clinthera.2014.10.003Get rights and content

Abstract

Purpose

The mechanisms by which depressive symptoms negatively affect clinical outcomes in patients with coronary artery disease (CAD) remain poorly understood. Previous interventions that have attempted to treat depressive symptoms in patients with CAD to improve their clinical outcomes have been disappointing. Our objectives were, among a cohort of CAD patients, to evaluate the impact of depressive symptoms over time, controlling for comorbidity, in determining both successful long-term lifestyle change (ie, increased physical activity), and cardiovascular morbidity and mortality outcomes. In addition, we examined the impact of physical activity changes over time on 2 known mediators of cardiovascular morbidity: parasympathetic tone and inflammation.

Methods

Clinical data were previously collected (2004–2006) from 242 elective/urgent coronary angioplasty patients who participated in a prospective randomized controlled trial evaluating the efficacy of a behavioral intervention versus an educational control to motivate physical activity over 12 months. Exclusion criteria included: (1) inability to walk; (2) enrollment in other risk-reduction trials; (3) non-English speaking; and (4) lack of cardiologist’s permission to increase physical activity. Participants were assessed every 2 months for interval clinical events and physical activity. In addition, biomarkers were collected at baseline and at 12 months in a subset of 54 participants; these biomarkers included low-frequency heart rate variability (lfHRV), high-frequency heart rate variability (hfHRV), serum C-reactive protein, interleukin-6, and salivary cortisol.

Findings

The mean age of participants was 63 years and 30% were female. Overall, 37% had high depressive symptoms at baseline. Patients with high depressive symptoms who achieved an increase in physical activity of ≥336 kilocalories(kcal)/week by 12 months had significantly lower rates of cardiovascular morbidity/mortality (5.1% vs. 21.3%; odds ratio [OR], 0.20, [95% CI, 0.04–0.98]; P = 0.03). In a multivariate model examining cardiovascular morbidity/mortality in patients with high depressive symptoms, an increase in physical activity of ≥336 kcal/week reduced the risk of new cardiovascular morbidity/mortality (OR, 0.11 [95% CI, 0.02–0.81]; P < 0.03), and comorbidity increased the risk (OR, 1.58 [95% CI, 1.18–2.13]; P = 0.002). In a generalized structural equation model, increasing physical activity by ≥336 kcal/week decreased the risk of complications, and comorbidity increased the risk. Furthermore, increasing physical activity (≥336 kcal/week) predicted an increase in hfHRV, a marker of parasympathetic tone, and the increase in hfHRV predicted a reduction in the proinflammatory mediators interleukin-6 and C-reactive protein.

Implications

This study found a threshold in physical activity in CAD patients with depressive symptoms that is associated with a decrease in cardiovascular morbidity and mortality. Exercise maintenance at this level may improve clinical outcomes via enhanced parasympathetic tone and decreased inflammation. ClinicalTrials.gov identifier: NCT00248846.

Introduction

Among patients with coronary artery disease (CAD), depression (including both major depressive disorder and depressive symptoms) is common.1, 2, 3 Patients with CAD who have major depression or high levels of depressive symptoms are at increased risk for morbidity and mortality.2, 3 In older adults, it is well established that patients with depressive symptoms frequently present with increased medical comorbidity.4 Evidence also suggests that, particularly in older subjects, depression may have an underlying vascular etiology.4, 5 Given that depression, depressive symptoms, and medical comorbidity6 are all important predictors of subsequent adverse outcomes, including increased morbidity and mortality, decreased functional status, and greater resource utilization, the potential for confounding is considerable.4

The mechanisms by which depressive symptoms negatively affect clinical outcomes (eg, cardiovascular morbidity and mortality) in patients with CAD remain poorly understood. In a 5-year longitudinal study of >1000 participants with CAD, the association between depressive symptoms and adverse cardiovascular events was largely explained by physical inactivity, which was associated with a 44% higher rate of cardiovascular events.7

Patients with CAD who increase their physical activity can achieve significant reductions in morbidity and mortality.8, 9 However, randomized trial data are sparse. Unfortunately, and for many psychosocial, medical, and motivational reasons, only a small percentage of people with CAD are successful at maintaining long-term lifestyle changes such as increased physical activity.10

Physical activity may play a particularly important role in reducing the risk of cardiovascular events among CAD patients with depressive symptoms. Of note, increased physical activity may ameliorate depressive symptoms; by itself, an intensive 16-week aerobic exercise regimen has been shown to be as effective as pharmacologic therapy in treating older adults for major depressive disorder.11 However, CAD patients with depressive symptoms are less successful in increasing physical activity over 12 months compared with those without depressive symptoms.12

Physical activity may also reduce the risk of cardiovascular events by suppressing inflammation. Inflammation is known to be an important pathophysiologic factor in cardiovascular disease progression,13, 14 and a large body of research has shown that depressive symptoms are associated with increased inflammation.15, 16 Exercise interventions have been shown to reduce inflammation in patients with CAD.17 Moreover, low parasympathetic tone has been linked to poor prognosis, more severe symptoms, and mortality from cardiovascular disease.18, 19 Physical activity can increase parasympathetic tone,20, 21 which is low in patients with major depression,22 and functions to both increase emotional regulation23 and suppress inflammation.24, 25

The objectives of the present study were, among a cohort of post coronary angioplasty patients, to evaluate the impact of depressive symptoms over time, controlling for comorbidity, in determining: (1) successful long-term lifestyle change (ie, increased physical activity); and (2) cardiovascular morbidity and mortality outcomes. In addition, we examined the impact of physical activity changes over time on 2 known mediators of cardiovascular morbidity: parasympathetic tone and inflammation.

Section snippets

Study Design

Data were collected between October 2004 and October 2006 at a tertiary academic medical center in New York City. Participants were enrolled in a National Heart, Lung, and Blood Institute–funded prospective, randomized controlled trial evaluating the efficacy of a behavioral medicine intervention versus an educational control to motivate physical activity over 12 months. The methods have been described previously.26 A subgroup of patients were recruited from the randomized trial for a

Results

Overall, 2605 patients with CAD were screened between October 2004 and October 2006.26 Of these, 242 patients were randomized to treatment and enrolled in the study. Attrition was 4.5%, and 2.1% of the participants died.

Discussion

To our knowledge, this is the first report of a threshold in physical activity in CAD patients with depressive symptoms that is associated with a reduction in cardiovascular morbidity and mortality. The notion that exercise augmentation at this level may improve clinical outcomes via enhanced parasympathetic tone and decreased inflammation is supported by our data. In this secondary data analysis of a randomized controlled trial that focused on patients with high depressive symptoms, we found

Conclusions

Our results reinforce the benefits of physical activity in high-risk CAD patients with high depressive symptoms and extend the literature in several important ways. First, we have documented a clinically important threshold in physical activity (ie, ≥336 kcal/week) that is associated with a significant decrease in cardiovascular morbidity and mortality in CAD patients with high depressive symptoms. Second, we have the benefit of 12 months of follow-up, which underscores the challenges of

Conflicts of Interest

■ ■ ■

Conflicts of Interest

The authors have indicated that they have no conflicts of interest regarding the content of this article.

Acknowledgments

The study was supported by grant 1N01-HC-25196 from the National Heart, Lung, and Blood Institute.

Dr. Peterson is the recipient of a Paul B. Beeson Award from the National Institute on Aging, the American Federation for Aging Research, The John A. Hartford Foundation, and The Atlantic Philanthropies under award K23AG042869.

Drs. Peterson, Altemus, Wells and Charlson had full access to all study data and responsibility for the integrity of the data and the accuracy of the data analysis. Peterson,

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