From the Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada.
Circ Res. 2017 Feb 17;120(4):681-691. doi: 10.1161/CIRCRESAHA.116.309306. Epub 2016 Nov 22.
Calcific aortic stenosis (AS) is characterized by calcium deposition in valve leaflets. However, women present lower aortic valve calcification loads than men for the same AS hemodynamic severity.
We, thus, aimed to assess sex differences in aortic valve fibrocalcific remodeling.
One hundred and twenty-five patients underwent Doppler echocardiography and multidetector computed tomography within 3 months before aortic valve replacement. Explanted stenotic tricuspid aortic valves were weighed, and fibrosis degree was determined. Sixty-four men and 39 women were frequency matched for age, body mass index, hypertension, renal disease, diabetes mellitus, and AS severity. Mean age (75±9 years), mean gradient (41±18 mm Hg), and indexed aortic valve area (0.41±0.12 cm/m) were similar between men and women (all ≥0.18). Median aortic valve calcification (1973 [1124-3490] Agatston units) and mean valve weight (2.36±0.99 g) were lower in women compared with men (both <0.0001). Aortic valve calcification density correlated better with valve weight in men (=0.57; <0.0001) than in women (=0.26; =0.0008). After adjustment for age, body mass index, aortic valve calcification density, and aortic annulus diameter, female sex was an independent risk factor for higher fibrosis score in AS valves (=0.003). Picrosirius red staining of explanted valves showed greater amount of collagen fibers (=0.01), and Masson trichrome staining revealed a greater proportion of dense connective tissue (=0.02) in women compared with men.
In this series of patients with tricuspid aortic valve and similar AS severity, women have less valvular calcification but more fibrosis compared with men. These findings suggest that the pathophysiology of AS and thus potential targets for drug development may be different according to sex.
钙化性主动脉瓣狭窄（AS）的特征是瓣叶钙沉积。然而，对于相同严重程度的 AS 血流动力学，女性主动脉瓣钙化负荷低于男性。
我们旨在评估主动脉瓣纤维钙化重塑的性别差异。
125 例患者在主动脉瓣置换前 3 个月内行多普勒超声心动图和多排螺旋 CT 检查。取出的狭窄三尖瓣主动脉瓣称重，并确定纤维化程度。64 名男性和 39 名女性按年龄、体重指数、高血压、肾脏疾病、糖尿病和 AS 严重程度进行频数匹配。男性和女性的平均年龄（75±9 岁）、平均梯度（41±18mmHg）和指数化主动脉瓣面积（0.41±0.12cm/m）相似（均≥0.18）。女性的主动脉瓣钙化中位数（1973[1124-3490]Agatston 单位）和平均瓣重（2.36±0.99g）低于男性（均<0.0001）。主动脉瓣钙化密度与男性瓣重相关性更好（r=0.57；<0.0001），而与女性相关性更差（r=0.26；=0.0008）。调整年龄、体重指数、主动脉瓣钙化密度和主动脉瓣环直径后，女性是 AS 瓣膜纤维化评分较高的独立危险因素（=0.003）。与男性相比，女性的三尖瓣主动脉瓣标本中天狼星红染色胶原纤维量更大（=0.01），Masson 三色染色显示致密结缔组织比例更高（=0.02）。
在这一系列三尖瓣主动脉瓣和相似 AS 严重程度的患者中，女性的瓣叶钙化较少，但纤维化程度高于男性。这些发现表明，AS 的病理生理学，以及因此药物开发的潜在靶点可能因性别而异。
