Abstract

BackgroundPremenopausal women have fewer cardiovascular disease (CVD) events than postmenopausal women and age-matched men, but the reasons are not fully understood. Coronary endothelial function (CEF), a barometer of coronary vascular health, promises important insights into age and sex differences in atherosclerotic CVD risk, but has not been well characterized in healthy individuals because of the invasive nature of conventional CEF measurements. Recently developed magnetic resonance imaging (MRI) methods were used to quantify CEF (coronary area and flow changes in response to isometric handgrip exercise (IHE), an endothelial-dependent stressor) to test the hypothesis that healthy women have better CEF compared to men particularly at a younger age.MethodsThe study participants were 50 healthy women and men with no history of coronary artery disease (CAD) or traditional CV risk factors and Agatston coronary calcium score (on prior CT) <10 for those ≥ 50 years. Coronary cross-sectional area (CSA) measurements and flow-velocity encoded images (CBF) were obtained at baseline and during continuous IHE using 3T breath-hold cine MRI-IHE. CEF (%change in CSA and CBF with IHE) comparisons were made according to age and sex, and all women ≥50 years were post-menopausal.ResultsIn the overall population, there were no differences in CEF between men and women. However, when stratified by age and sex the mean changes in CSA and CBF during IHE were higher in younger premenopausal women than older postmenopausal women (%CSA: 15.2±10.6% vs. 7.0±6.8%, p = 0.03 and %CBF: 59.0±37.0% vs. 30.5±24.5% p = 0.02). CBF change was also nearly two-fold better in premenopausal women than age-matched men (59.0±37.0% vs. 33.6±12.3%, p = 0.03).ConclusionsPremenopausal women have nearly two-fold better mean CEF compared to postmenopausal women. CEF, measured by CBF change is also better in premenopausal women than age-matched men but there are no sex differences in CEF after menopause. Fundamental age and sex differences in CEF exist and may contribute to differences in the development and clinical manifestations of atherosclerotic CVD, and guide future trials targeting sex-specific mechanisms of atherogenesis.

Highlights

  • Despite declines in cardiovascular disease (CVD) mortality rates in the United States over the past several decades, CVD is still the leading cause of morbidity and mortality in women [1]

  • When stratified by age and sex the mean changes in cross-sectional area (CSA) and CBF during isometric handgrip exercise (IHE) were higher in younger premenopausal women than older postmenopausal women (%CSA: 15.2 ±10.6% vs. 7.0±6.8%, p = 0.03 and %CBF: 59.0±37.0% vs. 30.5±24.5% p = 0.02)

  • Coronary endothelial function (CEF), measured by CBF change is better in premenopausal women than age-matched men but there are no sex differences in CEF after menopause

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Summary

Introduction

Despite declines in cardiovascular disease (CVD) mortality rates in the United States over the past several decades, CVD is still the leading cause of morbidity and mortality in women [1]. Some lines of research show that peripheral endothelial function measured by flow mediated vasodilation (FMD) of the brachial artery decreases with age in a gradual manner in men beginning in the fifth decade, while it remains preserved in young women followed by a more rapid decline in postmenopausal women in the sixth decade [12, 13]. Coronary endothelial function (CEF), a barometer of coronary vascular health, promises important insights into age and sex differences in atherosclerotic CVD risk, but has not been well characterized in healthy individuals because of the invasive nature of conventional CEF measurements. Developed magnetic resonance imaging (MRI) methods were used to quantify CEF (coronary area and flow changes in response to isometric handgrip exercise (IHE), an endothelial-dependent stressor) to test the hypothesis that healthy women have better CEF compared to men at a younger age

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