IntroductionThere are significant sex differences in the prevalence and severity of cardiac calcifying processes. Women harbour more severe mitral annular calcification (MAC), while men exhibit worse aortic valve (AVC) and coronary artery (CAC) calcification. To better understand these differences, we investigated the correlates of cardiac calcification according to sex.MethodsWe conducted a cross-sectional study of 406 patients with ≥mild aortic stenosis (AS) defined by an aortic valve area ≤1.5 cm2, a peak aortic jet velocity >2.0 m/s, or a mean transvalvular gradient >15 mm Hg. Doppler-echocardiography and non-contrast multidetector CT were performed concomitantly to assess AS and cardiac calcifications.ResultsMean age was 71±11 years and 33% were women. The AS haemodynamics were not significantly different between sexes (all p>0.50), with a mean indexed aortic valve area of 0.59±0.21 cm2/m2, peak aortic jet velocity of 2.78 (2.37–3.68) m/s, and mean gradient of 17.9 (12.8–31.3) mm Hg for the whole cohort. Compared with men, women harboured lower AVC (480 (222–1191) vs 1003 (484–2329) Agatston unit, AU; p<0.0001) and CAC (366 (50–914) vs 618 (167–1357) AU; p=0.007), but more severe MAC (60 (1–887) vs 48 (0–351) AU; p=0.08) and ascending aorta calcification (227 (43–863) vs 142 (7–493) AU; p=0.03). After comprehensive adjustment, sex remained an independent predictor of each cardiac calcification subtype (all p<0.02) except for the ascending aorta (p=0.32). In multivariable analysis, certain variables, like age or bicuspid aortic valve, were associated with the calcification scores in both sexes. Sex-specific predictors of calcification burden were absence of angiotensin receptor blockers (β=−0.26; p=0.007) and renal impairment (β=0.26; p=0.003) for AVC, and bisphosphonates (β=0.20; p=0.05) for CAC in women; coronary artery disease (β=0.25; p=0.001) for AVC, and angiotensin receptor blockers (β=0.19; p=0.02) and calcium/vitamin D (β=0.15; p=0.02) for MAC in men.ConclusionIn AS, factors associated with cardiac valvular and arterial calcification differ between sexes, suggesting an important contributory role of sex in the pathophysiology of these calcifying processes.

Introduction: It has been shown that women present lower coronary artery (CAC) and aortic valve calcification (AVC) loads while heavier mitral annular calcification (MAC) than men. However, the sex-specific predictors to these cardiac calcifications remain poorly characterized. Methods: We conducted a cross-sectional study in patients with at least mild AS (indexed aortic valve area: AVAi < 1.5 cm 2 /m 2 , Peak aortic jet velocity: Vpeak > 2.0 m/s, or Mean gradient: MG >15 mmHg). Doppler-echocardiography and non-contrast multidetector compute tomography were performed within 3 months. Ascending aorta calcification (AAC), AVC, CAC and MAC scores were measured using the Agatston method. Descriptive statistical analyses (t-test, Wilcoxon, univariate and multivariate analysis) were performed. Results: We studied 406 patients (71±11 years, 33% women) with AVAi= 0.59±0.21 cm 2 /cm 2 , Vpeak= 3.1±9.8 m/s, MG= 24.7±17.8 mmHg (equivalent between men and women, all p>0.34). Women present less AVC (480[222-1191] vs 1005[485-2364]AU; p<0.0001), and CAC (366[50-914] vs 626[167-1354]AU; p=0.006), but more MAC (60[1-887] vs 48[0-363]AU; p=0.05) and AAC (227[43-863] vs 142[7-493]AU; p=0.03) than men. Even after comprehensive adjustment, sex remained an independent predictor of each cardiac calcification (all p<0.01). In multivariate analysis, correlates with higher AVC or higher MAC were sex dependent (cf. table). Collinearity was avoided with all variance inflating factor <2.5. Conclusion: In AS patients, sex is a powerful and independent predictor of cardiac calcifications. Moreover, predictors of valvular calcification appear to be sex specific.