Sex, Microvascular Dysfunction, and Long-Term Outcomes

Quick Takes

  • There were no sex differences in index of microcirculatory resistance (IMR) and IMR did not predict clinical events at 5 years among men or women.
  • Women have faster resting blood flow compared to men.
  • Clinical relevance of this difference remains unknown.

Study Questions:

What is the relationship between sex and microvascular dysfunction as assessed by index of microcirculatory resistance (IMR), and long-term outcomes?


Four hundred and thirty-four patients (133 women and 301 men) underwent coronary flow reserve (CFR), IMR, fractional flow reserve (FFR), and quantitative coronary angiography. Clinical outcomes were assessed by major adverse cardiovascular events (MACE) of cardiac death, myocardial infarction, and revascularization during 5 years of follow-up.


Women had milder epicardial disease compared with men (FFR: 0.91 [interquartile range (IQR), 0.87-0.96] vs. 0.90 [IQR, 0.86-0.95]; p = 0.037). IMR was similar between the sexes, but CFR was lower in women (2.69 [IQR, 2.08-3.90] vs. 3.20 [IQR, 2.20-4.31]; p = 0.006) due to a shorter resting mean transit time in women, whereas hyperemic mean transit times were similar. At 5-year follow-up, MACE was significantly lower in women compared with men (1.1% vs. 5.5%; p = 0.017). Sex, diabetes mellitus, and CFR were independent predictors for MACE for all patients. The risk of MACE was significantly higher in men with low versus high CFR (hazard ratio, 4.58; 95% confidence interval [CI], 1.85-11.3; p = 0.011), which was not seen in women.


There was no sex difference in microvascular function by IMR. CFR was lower in women due to a higher resting coronary flow; however, long-term clinical outcomes in deferred lesions were better in women compared with men.


The results of this analysis compared measures of coronary microvascular function using IMR (CFR and IMR) among men and women and evaluated long-term event rates. There were no significant differences in IMR between men and women; however, CFR was lower in women (due to higher resting blood flow). CFR <2.0 predicted clinical events in men over the long-term, but not women. Interpretation of findings is limited by a very low event rate among women (study was not powered for event rates studied) and vessel-specific (vs. patient-specific) analysis. Assessment, interpretation, and clinical implications of sex differences in coronary microvascular dysfunction remain incompletely understood and warrant continued investigation.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Vascular Medicine, SCD/Ventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging

Keywords: Coronary Angiography, Death, Sudden, Cardiac, Diabetes Mellitus, Fractional Flow Reserve, Myocardial, Hemodynamics, Hyperemia, Microcirculation, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Outcome Assessment (Health Care)

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