Traditional cardiovascular risk factors and coronary microvascular disease in women and men- a single center study
Authors: Zornitzki L , Shetrit A , Freund F , Frydman S , Banai A , Amar Shamir R , Ben-Shoshan J , Arbel Y , Banai S , Konigstein M 
Published: October 2024

Abstract

Introduction
Coronary microvascular dysfunction (CMD) is a common, often missed, cause for effort intolerance and angina symptoms, and is associated with adverse clinical outcomes. Risk factors for the development of CMD have not been fully elucidated, and studies examining sex associated differences in traditional cardiovascular risk factors (TCRs) for obstructive coronary artery disease (CAD) in patients with CMD have yielded conflicting results. Although several non-invasive methods for the evaluation of CMD exist, currently, catheter-based invasive assessment is the gold standard for the diagnosis of coronary microvascular dysfunction.

Purpose
To examine the association between TCR and CMD and sex associated differences in TCR, in a prospective cohort of patients undergoing invasive microvascular function evaluation in a large tertiary medical center.

Methods
In this single center, prospective registry, we enrolled patients with non-obstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Measurements of microvascular function included CFR, IMR, RRR as well as FFR. Pathologic CFR was defined as &lt;2.5 or &lt;2. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models.

Results
Overall, 245 patients with non-obstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range [IQR]: 59,75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men in the entire cohort (59.0% vs. 57.0%; p=0.77). In 41 patients diagnosed with functional microvascular dysfunction there were more women than men (70.7% vs. 29%). When using a threshold of CFR&lt;2.5 no association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (CFR) (β=-0.29; p&lt;0.01 and β=-0.15; p=0.05, respectively) and lower resistive reserve ratio (RRR) (β=-0.28; p&lt;0.01 and β=-0.17; p=0.04, respectively). When using a threshold of &lt;2.0 for CFR similar results were found.

Conclusion
The prevalence of TCRs was similar in patients with and without CMD. In women, older age and previous IHD were associated with lower CFR and RRR values while no association between TCRs and indices of CMD was found in men. It is likely that there are other, currently unknown risk factors for CMD as well as unique risk factors for each of its endotypes, beyond TCRs. It is unclear which parameter of microvascular dysfunction is the most accurate, and whether different parameters should be used in women and men. Large-scale multi-center studies to further evaluate these issues are needed.Variables associated with CMDStudy inclusion process