Cardiovascular Reactivity to Mental Stress and Adverse Cardiovascular Outcomes in Patients With Coronary Artery Disease

J Am Heart Assoc. 2025 Jan 23:e034683. doi: 10.1161/JAHA.124.034683. Online ahead of print.

Abstract

Background: Acute psychological stress may induce physiological changes predisposing individuals to adverse health outcomes through hemodynamic and vascular effects. We studied the association between the aggregated stress-induced changes in hemodynamic and vascular function tests with adverse cardiovascular outcomes in patients with coronary artery disease, after adjusting for sociodemographic and clinical factors.

Methods and results: Individuals with stable coronary artery disease from 2 prospective cohort studies were studied. Hemodynamic reactivity, changes in endothelial function, and vasoconstriction during mental stress were evaluated using changes in rate-pressure product, brachial artery flow-mediated vasodilation, and peripheral arterial tonometry, respectively. A cardiovascular reactivity risk score was calculated by allotting 0 to 3 points for each quartile of increasing abnormality for each of the 3 reactivity responses and summing the quartile points from the MIPS (Mental Stress Ischemia Prognosis Study) to yield a cardiovascular reactivity risk score ranging from 0 to 9. The outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and heart failure hospitalizations during follow-up. A total of 629 participants were included. After adjustment for demographic and traditional risk factors, a blunted hemodynamic response, a greater decrease in flow-mediated vasodilation, and a greater degree of peripheral vasoconstriction to mental stress were all independently associated with a higher risk of adverse outcomes in both cohorts. By adding the cardiovascular reactivity risk score, the C-statistic increased significantly by 10% (P<0.001).

Conclusions: Among individuals with stable coronary artery disease, a risk score derived from cardiovascular reactivity to mental stress was predictive of adverse cardiovascular outcomes beyond traditional cardiovascular risk factors.

Keywords: adverse outcomes; coronary artery disease; endothelial function; hemodynamic reactivity; mental stress; vasoconstriction.