Psychological distress as a risk factor for cardiovascular events: pathophysiological and behavioral mechanisms

J Am Coll Cardiol. 2008 Dec 16;52(25):2156-62. doi: 10.1016/j.jacc.2008.08.057.


Objectives: This study sought to estimate the extent to which behavioral and pathophysiological risk factors account for the association between psychological distress and incident cardiovascular events.

Background: The intermediate processes through which psychological distress increases the risk of cardiovascular disease (CVD) are incompletely understood. An understanding of these processes is important for treating psychological distress in an attempt to reduce CVD risk.

Methods: In a prospective study of 6,576 healthy men and women (ages 50.9 +/- 13.1 years), we measured psychological distress (using the 12-item version of the General Health Questionnaire >or=4) and behavioral (smoking, alcohol, physical activity) and pathophysiological (C-reactive protein, fibrinogen, total and high-density lipoprotein cholesterol, obesity, hypertension) risk factors at baseline. The main outcome was CVD events (hospitalization for nonfatal myocardial infarction, coronary artery bypass, angioplasty, stroke, heart failure, and CVD-related mortality).

Results: Cigarette smoking, physical activity, alcohol intake, C-reactive protein, and hypertension were independently associated with psychological distress. There were 223 incident CVD events (63 fatal) over an average follow-up of 7.2 years. The risk of CVD increased in relation to presence of psychological distress in age- and sex-adjusted models (hazard ratio: 1.54, 95% confidence interval: 1.09 to 2.18, p = 0.013). In models that were adjusted for potential mediators, behavioral factors explained the largest proportion of variance ( approximately 65%), whereas pathophysiological factors accounted for a modest amount (C-reactive protein approximately 5.5%, hypertension, approximately 13%).

Conclusions: The association between psychological distress and CVD risk is largely explained by behavioral processes. Therefore, treatment of psychological distress that aims to reduce CVD risk should primarily focus on health behavior change.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcohol Drinking / adverse effects
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / physiopathology*
  • Cardiovascular Diseases / psychology*
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Disease Progression
  • Female
  • Fibrinogen / metabolism
  • Health Behavior
  • Humans
  • Hypertension / complications
  • Inflammation / complications
  • Male
  • Middle Aged
  • Motor Activity
  • Obesity / complications
  • Odds Ratio
  • Prospective Studies
  • Psychological Tests
  • Psychometrics
  • Risk Factors
  • Smoking / adverse effects
  • Stress, Psychological / blood
  • Stress, Psychological / complications*
  • Surveys and Questionnaires
  • United Kingdom / epidemiology


  • Biomarkers
  • Cholesterol, HDL
  • Fibrinogen
  • C-Reactive Protein
  • Cholesterol