Mental stress promotes endothelial dysfunction, increases odds of MACE

Transient endothelial dysfunction stemming from mental duress was associated with a 78% increase in the incidence of major adverse cardiovascular events (MACE) in a study of patients with stable coronary artery disease (CAD), providing scientists with a look at just how much psychological stress can influence our risk of CVD.

Stress has long been associated with heightened CV morbidity and mortality, lead author Bruno B. Lima, MD, PhD, and colleagues at Emory University wrote in JAMA Cardiology. But the pathway through which stress elevates those risk factors is less clear.

“One postulated mechanism is that chronic or repeated exposure to psychological stress, through activation of the sympathoadrenal pathways, causes cumulative wear and tear of the endothelial lining of blood vessels, eventually leading to endothelial dysfunction, accelerated atherogenesis and elevated incidence of cardiovascular events,” Lima et al. said in the journal. “However, there are few empirical data in humans in support of this theoretical model.”

Lima’s team conducted a cohort study within an Emory-affiliated hospital network between 2011 and 2014, recruiting 569 patients with stable CAD for the effort. The researchers measured flow-mediated vasodilation (FMD) for each participant before and 30 minutes after a public-speaking mental stress task.

Looking at the link between prestress, poststress and delta FMD (poststress minus prestress levels) with a composite endpoint of cardiovascular death, MI, unstable angina leading to revascularization and heart failure hospitalization, the authors found that CAD patients who underwent the lab mental stress test were more likely to exhibit symptoms of endothelial dysfunction.

After adjusting for sociodemographic factors, medical history and depression, Lima and colleagues reported that 360 patients—63.3% of the total cohort—developed transient endothelial dysfunction after the public speaking task. Flow-mediated vasodilation decreased from an average of 4.8% before mental stress to 3.9% after mental stress, translating to a 23% overall reduction.

During a mean follow-up period of three years, 74 patients experienced a major adverse CV event. The presence of transient endothelial dysfunction with mental stress was tied to a 78% increase in the incidence of MACE; both delta FMD and poststress FMD were linked to MACE.

“In this study, we demonstrate that poststress FMD levels are more robustly associated with MACE than prestress measurements are,” Lima et al. wrote. “In addition, we have recently shown that mental stress promotes endothelium-dependent coronary vasoconstriction. Combined with prior observations that brachial arterial FMD levels reflect coronary vascular endothelial function, the current findings imply that the stress-induced transient endothelial dysfunction in the peripheral circulation is reflected in the coronary vascular bed.”

The authors said they believe their results could spur the development and validation of mental stress-testing methods in the clinic that could go hand-in-hand with vascular assessments. They wrote that further studies will be needed to determine whether the changes they observed in the lab reflect the same endothelial responses people experience during everyday stressors.