Introduction: Approximately 40% of patients undergoing diagnostic coronary angiography for chest pain have no significant coronary stenosis. In such cases, functional disorders including vasospastic angina (VSA) and coronary microvascular dysfunction may cause myocardial ischemia. However, coronary microvascular function of VSA patients remains to be elucidated, especially in terms of sex differences.
Methods and Results: We enrolled 180 consecutive patients with suspected angina and unobstructive coronary arteries (62.7±12.4 [SD] years-old, M/F 112/68). We divided them into two groups according to the results of acetylcholine provocation test; VSA group (n=123) and non-VSA group (n=57). To assess their coronary microvascular function, we measured coronary flow reserve (CFR) and index of microcirculation resistance (IMR) in the left anterior descending artery with a pressure-temperature sensor guidewire. CFR was calculated as resting mean transient time (Tmn) divided by hyperemic Tmn, and IMR as the distal coronary pressure multiplied by the hyperemic Tmn. Although there was no significant difference in CFR between VSA and non-VSA groups (2.74±1.42 vs. 2.86±1.34, P=0.52), IMR at hyperemic state induced by intravenous adenosine was significantly higher in the VSA group than in the non-VSA group (20.7±12.6 vs. 16.8±8.2, P=0.04). Importantly, the difference in IMR between the VSA and the non-VSA groups was abolished after intracoronary administration of fasudil, a selective Rho-kinase inhibitor (17.9±9.8 vs. 18.1±10.6, P=0.86). Furthermore, we examined sex differences in those two parameters in VSA patients (M/F 75/48). Intriguingly, there was no significant difference in IMR between male and female patients (M, 21.3±14.4 vs. F, 19.8±9.0, P=0.88), whereas CFR was significantly lower in female VSA patients than in male VSA patients (M, 2.93±1.49 vs. F, 2.45±1.27, P<0.05). Furthermore, intracoronary administration of fasudil eliminated the sex difference in CFR among VSA patients (M, 3.28±1.73 vs. F, 3.04±1.80, P=0.31).
Conclusions: These results indicate that coronary microvascular dysfunction is present in VSA patients, especially in female VSA patients, for which Rho-kinase activation may substantially be involved.