Mathews Lena, Iantorno Micaela, Schär Michael, Bonanno Gabriele, Gerstenblith Gary, Weiss Robert G, Hays Allison G
Department of Medicine, Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
Department of Radiology, Division of Magnetic Resonance Research, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2017 Oct 26;12(10):e0186448. doi: 10.1371/journal.pone.0186448. eCollection 2017.
Premenopausal 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.
The 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.
In 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).
Premenopausal 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.
绝经前女性发生心血管疾病(CVD)事件的次数少于绝经后女性和年龄匹配的男性,但其原因尚未完全明确。冠状动脉内皮功能(CEF)是冠状动脉血管健康的一项指标,有望为动脉粥样硬化性CVD风险的年龄和性别差异提供重要见解,但由于传统CEF测量具有侵入性,在健康个体中尚未得到充分研究。最近开发的磁共振成像(MRI)方法被用于量化CEF(冠状动脉面积和血流变化对静态握力运动(IHE)的反应,IHE是一种内皮依赖性应激源),以检验以下假设:健康女性,尤其是在较年轻的时候,与男性相比具有更好的CEF。
研究参与者为50名无冠状动脉疾病(CAD)病史或传统心血管风险因素的健康女性和男性,对于年龄≥50岁的参与者,其阿加斯顿冠状动脉钙化评分(基于之前的CT)<10。在基线和持续IHE期间,使用3T屏气电影MRI-IHE获得冠状动脉横截面积(CSA)测量值和流速编码图像(CBF)。根据年龄和性别对CEF(IHE时CSA和CBF的变化百分比)进行比较,所有≥50岁的女性均已绝经。
在总体人群中,男性和女性的CEF没有差异。然而,按年龄和性别分层时,年轻绝经前女性IHE期间CSA和CBF的平均变化高于老年绝经后女性(CSA变化百分比:15.2±10.6%对7.0±6.8%,p = 0.03;CBF变化百分比:59.0±37.0%对30.5±24.5%,p = 0.02)。绝经前女性的CBF变化也比年龄匹配的男性高出近两倍(59.0±37.0%对33.6±12.3%,p = 0.03)。
绝经前女性的平均CEF比绝经后女性高出近两倍。通过CBF变化测量的CEF在绝经前女性中也比年龄匹配的男性更好,但绝经后CEF不存在性别差异。CEF存在基本的年龄和性别差异,可能导致动脉粥样硬化性CVD发生发展和临床表现的差异,并为未来针对动脉粥样硬化性别特异性机制的试验提供指导。