Excess Cardiovascular Risk in Women With Low Flow Reserve

Study Questions:

Does coronary flow reserve (CFR) identify women at increased risk for cardiovascular (CV) events?


Consecutive patients who were referred for invasive coronary angiography (n = 329) comprised the study population for this analysis. Patients all had a stress test prior to angiography, which included myocardial perfusion positron emission tomography (PET), and had a left ventricular ejection fraction over 40%. Follow-up was a median of 3 years. The primary outcome of interest was a composite endpoint of major adverse CV events including CV death and hospitalization for nonfatal myocardial infarction (MI) or heart failure.


A total of 329 patents were included in the analysis, of which 43% were women. Women had lower pretest clinical score, rates of prior MI, and burden of coronary artery disease (CAD) by angiography compared with men. However, women had a greater risk for CVD events compared with men, even after adjustment for traditional risk factors, imaging findings, and early revascularization (adjusted hazard ratio, 2.05; 95% confidence interval, 1.05-4.02; p = 0.03). Impaired CFR was similar among men and women. Among patients with low CFR (<1.6, n = 163), women had a higher frequency of nonobstructive CAD, while men had a higher frequency of severely obstructive CAD (p = 0.002). After adjustment for CFR, the effect of sex on outcomes was no longer significant. When stratified by sex and CFR, only women with severely impaired CFR demonstrated significantly increased adjusted risk of CV events (p < 0.0001, p for interaction = 0.04).


The investigators concluded that women referred for coronary angiography had significantly lower burden of obstructive CAD relative to men, but were not protected from CV events. Excess CV risk in women was independently associated with impaired CFR, representing a hidden biological risk, and a phenotype less amenable to revascularization. Impaired CFR, particularly absent severely obstructive CAD, may represent a novel target for CVD risk reduction.


Prior work has also observed that women presenting with cardiac events are more likely to present with nonobstructive CAD compared with men; however, this study examines the risk for future CV events associated with low CFR. The observation of significant effect modification by sex and CFR suggests that research should focus on the biology of gender-related differences in ischemic heart disease, which could explain these differences between men and women. Clinical research effort also should focus on understanding how to mitigate the risk associated with low CFR among both men and women.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Nuclear Imaging

Keywords: Acute Coronary Syndrome, AHA Annual Scientific Sessions, Cardiovascular Diseases, Coronary Angiography, Coronary Artery Disease, Exercise Test, Fractional Flow Reserve, Myocardial, Heart Failure, Myocardial Infarction, Myocardial Ischemia, Positron-Emission Tomography, Primary Prevention, Risk Factors, Stroke Volume, Women

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