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Mental Stress–Induced Endothelial Dysfunction and Adverse CV Events in CAD
Study Questions:
What is the association between mental stress-induced impairment in endothelium-dependent relaxation as assessed by brachial artery flow-mediated vasodilation and adverse cardiovascular outcomes among individuals with stable coronary artery disease (CAD)?
Methods:
The investigators conducted a cohort study at a university-affiliated hospital network between June 2011 and August 2014. A cohort of individuals with stable CAD were included. Data analysis took place from November 2018 to May 2019. Study participants were subjected to a laboratory mental stress task (public speaking). Flow-mediated vasodilation was measured before and 30 minutes after a public-speaking mental stress task. The authors examined the association of the rest (prestress), poststress, and δ flow-mediated vasodilation (poststress minus prestress levels) with an adjudicated composite endpoint of adverse events, including cardiovascular death, myocardial infarction, unstable angina leading to revascularization, and heart failure hospitalization, after adjusting for sociodemographic factors, medical history, and depression. To investigate the association between flow-mediated vasodilation and cardiovascular events, prestress, poststress, and δ flow-mediated vasodilation levels were examined as continuous variables in Fine and Gray subdistribution hazard models with noncardiovascular death treated as the competing risk.
Results:
A total of 569 patients were included (mean [standard deviation] age, 62.6 [9.3] years; 420 men [73.8%]). Flow-mediated vasodilation decreased from a mean (standard deviation) of 4.8% (3.7%) before mental stress to 3.9% (3.6%) after mental stress (a 23% reduction; p < 0.001), and 360 participants (63.3%) developed transient endothelial dysfunction (a decrease in flow-mediated vasodilation). During a median (interquartile range) follow-up period of 3.0 (2.9-3.1) years, 74 patients experienced a major adverse cardiovascular event. The presence of transient endothelial dysfunction with mental stress was associated with a 78% increase (subdistribution hazard ratio [sHR], 1.78; 95% confidence interval [CI], 1.15-2.76) in the incidence of major adverse cardiovascular event. Both the δ flow-mediated vasodilation (sHR, 1.15; 95% CI, 1.03-1.27 for each 1% decline) and poststress flow-mediated vasodilation (sHR, 1.14; 95% CI, 1.04-1.24 for each 1% decline) were associated with major adverse cardiovascular event. Risk discrimination statistics demonstrated a significant model improvement after addition of either poststress flow-mediated vasodilation (change in the area under the curve, 0.05; 95% CI, 0.01-0.09) or prestress plus δ flow-mediated vasodilation (change in the area under the curve, 0.04; 95% CI, 0.00-0.08) compared with conventional risk factors.
Conclusions:
The authors concluded that transient endothelial dysfunction with mental stress was associated with adverse cardiovascular outcomes in patients with CAD.
Perspective:
This cohort study reports that a greater decrease in endothelium-dependent flow-mediated vasodilation provoked by mental stress is associated with higher rates of incident cardiovascular death and major adverse cardiovascular disease outcomes, independent of other patient characteristics and prestress flow-mediated vasodilation levels. These results point to endothelial responses to psychological stress as an important risk marker linking stress to adverse outcomes and disease progression in CAD patients. Furthermore, the current findings may potentially lead to the development and validation of mental stress–testing methods in conjunction with vascular assessments that could be applied in the clinical care environment, and the assessment of future interventions to ameliorate endothelial responses to stress or their adverse consequences.
Keywords: Acute Coronary Syndrome, Angina, Unstable, Coronary Artery Disease, Depression, Disease Progression, Endothelium, Heart Failure, Myocardial Infarction, Myocardial Ischemia, Risk Factors, Secondary Prevention, Stress, Psychological, Vasodilation
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