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Comparative Study
. 2015 Sep;8(11):1433-1441.
doi: 10.1016/j.jcin.2015.03.045.

Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease

Yuhei Kobayashi  1 , William F Fearon  1 , Yasuhiro Honda  1 , Shigemitsu Tanaka  1 , Vedant Pargaonkar  1 , Peter J Fitzgerald  1 , David P Lee  1 , Marcia Stefanick  1 , Alan C Yeung  1 , Jennifer A Tremmel  2
Affiliations
Comparative Study

Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease

Yuhei Kobayashi et al. JACC Cardiovasc Interv. 2015 Sep.

Abstract

Objectives: This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease.

Background: Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation.

Methods: We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia.

Results: All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn.

Conclusions: Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.

Keywords: coronary flow reserve; coronary microvascular resistance; physiology; sex.

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Figures

FIGURE 1
FIGURE 1. Schematic of Physiological Assessment Using a Single Coronary PressureWire
Image modified from Kobayashi and Fearon (9). CFR = coronary flow reserve; FFR = fractional flow reserve; IMR = the index of microcirculatory resistance; Pa = mean proximal coronary pressure; Pd = mean distal coronary pressure; and Tmn = mean transit time.
FIGURE 2
FIGURE 2. Comparison of CFR and IMR Between Women and Men
CFR is significantly lower in women than men. On the contrary, IMR, a direct measure of microcirculation, is similar. Abbreviations as in Figure 1.
FIGURE 3
FIGURE 3. Comparison of Tmn Between Women and Men
Resting Tmn is significantly shorter in women than men. On the contrary, hyperemic Tmn was similar. These findings suggest resting coronary flow is higher in women than men, whereas hyperemic coronary flow is similar. Tmn = mean transit time.
FIGURE 4
FIGURE 4. Comparison of Physiological Indexes According to Patient Sex and Vessel Size
ANOVA = analysis of variance; other abbreviations as in Figure 1.
See this image and copyright information in PMC

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