Coronary and Peripheral Vasomotor Responses to Mental Stress

Abstract

Background: Coronary microvascular dysfunction may contribute to myocardial ischemia during mental stress (MS). However, the role of coronary epicardial and microvascular function in regulating coronary blood flow (CBF) responses during MS remains understudied. We hypothesized that coronary vasomotion during MS is dependent on the coronary microvascular endothelial function and will be reflected in the peripheral microvascular circulation.

Methods and results: In 38 patients aged 59±8 years undergoing coronary angiography, endothelium-dependent and endothelium-independent coronary epicardial and microvascular responses were measured using intracoronary acetylcholine and nitroprusside, respectively, and after MS induced by mental arithmetic testing. Peripheral microvascular tone during MS was measured using peripheral arterial tonometry (Itamar Inc, Caesarea, Israel) as the ratio of digital pulse wave amplitude compared to rest (peripheral arterial tonometry ratio). MS increased the rate-pressure product by 22% (±23%) and constricted epicardial coronary arteries by -5.9% (-10.5%, -2.6%) (median [interquartile range]), P=0.001, without changing CBF. Acetylcholine increased CBF by 38.5% (8.1%, 91.3%), P=0.001, without epicardial coronary diameter change (0.1% [-10.9%, 8.2%], P=not significant). The MS-induced CBF response correlated with endothelium-dependent CBF changes with acetylcholine (r=0.38, P=0.03) but not with the response to nitroprusside. The peripheral arterial tonometry ratio also correlated with the demand-adjusted change in CBF during MS (r=-0.60, P=0.004), indicating similarity between the microcirculatory responses to MS in the coronary and peripheral microcirculation.

Conclusions: The coronary microvascular response to MS is determined by endothelium-dependent, but not endothelium-independent, coronary microvascular function. Moreover, the coronary microvascular responses to MS are reflected in the peripheral microvascular circulation.

Keywords: endothelial function; epicardial; flow; mental stress; microvascular; resistance.

Figure 1

Schematic flowchart of the study protocol and respective measurements. APV indicates average peak velocity; BP, blood pressure; HR, heart rate; MS, mental stress test; PAT, peripheral arterial tonometry.

Figure 2

Hemodynamic and coronary vascular responses during mental stress (MS). Bars and error bars represent the median change and 95% confidence interval, respectively. CBF indicates coronary blood flow; CI, confidence interval; CVR, coronary vascular resistance; HR, heart rate; MAP, mean arterial pressure.

Figure 3

Relationship between coronary blood flow (CBF) and epicardial responses during mental stress (MS) and acetylcholine infusion. r values are Spearman correlation coefficients. A, The solid line represents the line of best fit, and the dashed lines represent 95% confidence interval. B, The vertical and the horizontal reference lines (dashed) represent no change in epicardial diameter in response to acetylcholine and MS, respectively.

Figure 4

Relationship between coronary microvascular responses during mental stress and during (A) acetylcholine, (B) sodium nitroprusside, and (C) adenosine infusions. Subjects divided by median CBF responses. Bars and error bars represent the median change and 95% CI, respectively. CBF indicates coronary blood flow; CI, confidence interval; CVR, coronary vascular resistance.

Figure 5

Relationship between mental stress–induced digital microvascular response, measured as the peripheral arterial tonometry (PAT) ratio, and the coronary microvascular vasomotor response, measured as the coronary blood flow (CBF) response adjusted for the rate‐pressure product (RPP). The solid line represents the line of best fit, and the dashed lines represent the 95% confidence interval.