Cold pressor testing and sympathetic nervous system contribution to ischemia with no obstructive coronary artery disease: Results from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Project

Cold pressor testing (CPT) is a known stimulus of the sympathetic nervous system (SNS). To better understand sympathetic contribution to coronary blood flow regulation in women with suspected ischemia and no obstructive coronary arteries (INOCA), we compared myocardial perfusion reserve during CPT stress cardiac magnetic resonance (CMR) imaging between women with suspected INOCA and reference subjects. Prospective cohort. Academic hospital. 107 women with suspected INOCA and 21-age-matched reference women. CPT stress CMR was performed with measurement of myocardial perfusion reserve index (MPRI), adjusted for rate pressure product (MPRIRPP). Invasive coronary function testing in a subset of INOCA women (n = 42) evaluated for endothelial dysfunction in response to acetylcholine, including impaired coronary diameter response ≤0% and coronary blood flow response (ΔCBF) <50%. MPRIRPP. Compared to reference women, the INOCA group demonstrated higher resting RPP (p = 0.005) and CPT MPRIRPP (1.09 ± 0.36 vs 0.83 ± 0.18, p = 0.002). Furthermore, INOCA women with impaired ΔCBF (n = 23) had higher CPT MPRIRPP (p = 0.044) compared to reference women despite lower left ventricular ejection fraction (64 ± 7% vs 69 ± 2%, p = 0.005) and higher mass-to-volume ratio (0.79 ± 0.15 vs 0.62 ± 0.09, p < 0.0001). These differences in CPT MPRIRPP did not persist after adjusting for age, body mass index, and history of hypertension. CPT MPRIRPP among INOCA women did not differ based on defined acetylcholine responses. Myocardial perfusion reserve to CPT stress is greater among women with INOCA compared to reference subjects. This CPT response was also noted in women with coronary endothelial dysfunction, suggesting a greater contribution of the SNS to coronary flow than endothelial dysfunction. Therapies to modulate sympathetic activity should be studied in this population.