What is already known on this topic
- Epicardial coronary atherosclerosis of varying severity is prevalent among patients with ischaemia with no obstructive coronary artery disease (INOCA), although the pathophysiological associations between atherosclerosis and microvascular dysfunction remain uncertain.
What this study adds
- In this cross-sectional study of prospectively recruited individuals, clinical endotypes of INOCA were defined by coronary angiography, fractional flow reserve, thermodilution tests of microvascular function and responses to intracoronary infusion of acetylcholine. This was then correlated with the Gensini score, a quantitative measure of coronary plaque burden.
- Novel measures of coronary microvascular dysfunction, including reduced microvascular resistance reserve and resistive reserve ratio, and microvascular angina, were associated with higher Gensini scores.
How this study might affect research, practice or policy
- Our study identifies mechanistic associations between coronary atherosclerosis burden and microvascular dysfunction in INOCA, thereby reinforcing the importance of antiatherosclerosis therapy in this population.
Introduction
Many patients with suspected or proven myocardial ischaemia are found to have no flow-limiting disease in the epicardial circulation (ischaemia with no obstructive coronary artery disease (INOCA)). The Coronary Vasomotion Disorders International Study Group (COVADIS) have established criteria for the diagnosis microvascular and vasospastic angina (VSA). These conditions are prognostically important and, potentially, a therapeutic target. Guidelines recommend coronary function testing to aid clinical diagnosis. In the CorMicA trial, patients underwent invasive coronary function testing, to allow endotype classification according to COVADIS criteria: microvascular angina (MVA), VSA, both, or non-cardiac chest pain.
Epicardial coronary atherosclerosis of varying severity is prevalent among patients with INOCA, although the pathophysiological associations between atherosclerosis and microvascular dysfunction remain uncertain. Echavarria-Pinto et al studied 78 patients with ‘intermediate’ coronary artery disease. Coronary flow reserve (CFR) and Index of Microcirculatory Resistance (IMR) differed according to the distribution of coronary artery disease (focal vs diffuse). However, this cohort was relatively small, 41% of patients had flow-limiting atherosclerosis (fractional flow reserve (FFR) ≤0.80), acetylcholine vasoreactivity testing was not included, and substantive analyses in the subgroup of patients with non-flow-limiting atherosclerosis (FFR >0.80; n=54 arteries) were uncertain. While CFR reflects the combined vasodilator reserve of the epicardial coronary artery and microcirculation, specific associations between atherosclerosis burden and novel microvascular-specific indices are uncertain.
To address these knowledge gaps, we aimed to investigate the relationships between atherosclerosis and microvascular function in a well-defined, prospectively recruited population. The microvascular resistance reserve (MRR) and resistive reserve ratio (RRR) are novel indices. Unlike CFR, they are specific measures of microvascular function and independent of epicardial coronary atherosclerosis. We investigated potential associations between cumulative atherosclerotic plaque burden quantified using the Gensini score, novel invasive indices of coronary microvascular function and related INOCA endotypes. We hypothesised MRR and RRR are inversely correlated with atherosclerosis burden in this population.
