Coronary Vascular Function and Cardiomyocyte Injury: A Report From the WISE-CVD

Abstract

Objective: Women with symptoms or signs of myocardial ischemia but no obstructive coronary artery disease (INOCA) often have coronary vascular dysfunction and elevated risk for adverse cardiovascular events. We hypothesized that u-hscTnI (ultra-high-sensitivity cardiac troponin I), a sensitive indicator of ischemic cardiomyocyte injury, is associated with coronary vascular dysfunction in women with INOCA. Approach and Results: Women (N=263) with INOCA enrolled in the WISE-CVD study (Women's Ischemic Syndrome Evaluation-Coronary Vascular Dysfunction) underwent invasive coronary vascular function testing and u-hscTnI measurements (Simoa HD-1 Analyzer; Quanterix Corporation, Lexington, MA). Logistic regression models, adjusted for traditional cardiovascular risk factors were used to evaluate associations between u-hscTnI and coronary vascular function. Women with coronary vascular dysfunction (microvascular constriction and limited coronary epicardial dilation) had higher plasma u-hscTnI levels (both P=0.001). u-hscTnI levels were associated with microvascular constriction (odds ratio, 1.38 per doubling of u-hscTnI [95% CI, 1.03-1.84]; P=0.033) and limited coronary epicardial dilation (odds ratio, 1.37 per doubling of u-hscTnI [95% CI, 1.04-1.81]; P=0.026). u-hscTnI levels were not associated with microvascular dilation or coronary epicardial constriction.

Conclusions: Our findings indicate that higher u-hscTnI is associated with coronary vascular dysfunction in women with INOCA. This suggests that ischemic cardiomyocyte injury in the setting of coronary vascular dysfunction has the potential to contribute to adverse cardiovascular outcomes observed in these women. Additional studies are needed to confirm and investigate mechanisms underlying these findings in INOCA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00832702.

Keywords: INOCA; acetylcholine; cardiomyocyte injury; coronary artery disease; myocardial ischemia; risk; troponin I; vascular function.

Figure 1:. Distribution of Selected Coronary Vascular Function Testing in 263 Women with Evidence of Ischemia and no Obstructive Coronary Artery Disease.

Most women underwent evaluation of >1 coronary vascular function pathway. Green represents women who underwent evaluation of coronary microvascular dilation using coronary flow reserve (CFR); orange represents women who underwent evaluation of coronary microvascular constriction using coronary blood flow (CBF); yellow represents women who underwent evaluation of coronary epicardial constriction using change in coronary artery diameter in response to intracoronary acetylcholine (IC-Ach); blue represents women who underwent evaluation of coronary epicardial dilation using change in in response to intracoronary nitroglycerin (IC-NTG).

Figure 2:

Box Plots demonstrating the relationship between the ultra-high sensitivity troponin I (u hscTnI) levels (log transformed) and (A) Normal and limited coronary blood flow response to intra-coronary acetylcholine (normal response defined as an increase in coronary blood flow in response to acetylcholine by ≥50%), (B) Normal and limited microvascular dilation to intra-coronary adenosine (normal coronary flow reserve ≥2.32), (C) Normal and limited coronary dilation in response to intra-coronary acetylcholine (normal response defined as an increase in coronary artery diameter in response to acetylcholine by ≥0%), (D) Normal and limited coronary artery dilation in response to intra-coronary nitroglycerin (normal response defined as an increase in coronary artery diameter in response to nitroglycerin by ≥20%).