Racial Differences in Mental Stress-Induced Transient Endothelial Dysfunction and Its Association With Cardiovascular Outcomes

Abstract

Objective: This study aimed to investigate differences in transient endothelial dysfunction (TED) with mental stress in Black and non-Black individuals with coronary heart disease (CHD), and their potential impact on cardiovascular outcomes.

Methods: We examined 812 patients with stable CHD between June 2011 and March 2016 and followed through February 2020 at a university-affiliated hospital network. Flow-mediated vasodilation (FMD) was assessed before and 30 minutes after mental stress. TED was defined as a lower poststress FMD than prestress FMD. We compared prestress FMD, post-stress FMD, and TED between Black and non-Black participants. In both groups, we examined the association of TED with an adjudicated composite end point of cardiovascular death or nonfatal myocardial infarction (first and recurring events) after adjusting for demographic, clinical, and socioeconomic factors.

Results: Prestress FMD was lower in Black than non-Black participants (3.7 [2.8] versus 4.9 [3.8], p < .001) and significantly declined with mental stress in both groups. TED occurred more often in Black (76%) than non-Black patients (67%; multivariable-adjusted odds ratio = 1.6, 95% confidence interval = 1.5-1.7). Over a median (interquartile range) follow-up period of 75 (65-82) months, 142 (18%) patients experienced either cardiovascular death or nonfatal myocardial infarction. Black participants had a 41.9% higher risk of the study outcome than non-Black participants (95% confidence interval = 1.01-1.95). TED with mental stress explained 69% of this excess risk.

Conclusions: Among CHD patients, Black individuals are more likely than non-Black individuals to develop endothelial dysfunction with mental stress, which in turn explains a substantial portion of their excess risk of adverse events.

Figure 1:

Comparison of pre- and post-stress brachial artery flow mediated dilation in Blacks and non-Blacks (A). Incidence of transient endothelial dysfunction after mental stress in Black vs. non-Black participants. (B)

Figure 2:

Distribution of first and recurrent events for the study endpoints in Black (A) and non-Black (B) participants stratified by transient endosthelial dysfunction status. (+): Present; (−): Absent

Figure 3:

Multivariable analysis of the association of transient endothelial dysfunction with the primary endpoint (a composite of cardiovascular death or nonfatal first or recurring MI) among Black (Panel A) and non-Black (Panel B) participants. Models sequentially added sets of variables, and the percent effect explained was calculated as the percent change in hazard ratio compared to Model 1. Footnote: Socioeconomic factors included income (<35,000 vs. ≥35,000 per year), education (<12 years vs. ≥12 years), employment (not employed vs. employed fulltime or part-time). Clinical risk factors included body mass index, current smoking status, history of diabetes, hypertension, dyslipidemia, congestive heart failure, and current medications (beta-blockers, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and statins). Psychosocial risk factors included a composite distress score based on average ranks of 6 psychosocial scale scores (symptoms of depression, posttraumatic stress disorder, anger, anxiety, perceived stress, and hostility.

Figure 3:

Multivariable analysis of the association of transient endothelial dysfunction with the primary endpoint (a composite of cardiovascular death or nonfatal first or recurring MI) among Black (Panel A) and non-Black (Panel B) participants. Models sequentially added sets of variables, and the percent effect explained was calculated as the percent change in hazard ratio compared to Model 1. Footnote: Socioeconomic factors included income (<35,000 vs. ≥35,000 per year), education (<12 years vs. ≥12 years), employment (not employed vs. employed fulltime or part-time). Clinical risk factors included body mass index, current smoking status, history of diabetes, hypertension, dyslipidemia, congestive heart failure, and current medications (beta-blockers, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and statins). Psychosocial risk factors included a composite distress score based on average ranks of 6 psychosocial scale scores (symptoms of depression, posttraumatic stress disorder, anger, anxiety, perceived stress, and hostility.