title: Depression, coronary artery disease, and physical activity: how much exercise is enough?
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Clinical Epidemiology and Evaluative Sciences Research, Center for Integrative Medicine, Weill Cornell Medical College, New York, New York. Electronic address: jcpeters@med.cornell.edu.
authors.forename: Janey C
authors.initials: JC
authors.lastname: Peterson
authors.affiliation: Division of Clinical Epidemiology and Evaluative Sciences Research, Center for Integrative Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Charlson
authors.affiliation: Departments of Statistical Science and Social Statistics, Cornell University, Ithaca, New York.
authors.forename: Martin T
authors.initials: MT
authors.lastname: Wells
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, New York.
authors.forename: Margaret
authors.initials: M
authors.lastname: Altemus
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D003863:Depression / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D015444:Exercise; D005260:Female; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D012463:Saliva / Q000737:chemistry
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D002097:C-Reactive Protein; D006854:Hydrocortisone
keywords: coronary artery disease; depression; exercise; heart rate variability; interleukin-6