The aim of this study was to assess the impact of sex on the management and outcome of patients according to aortic stenosis (AS) severity. Sex differences in the management and outcome of AS are poorly understood. Doppler echocardiography data of patients with at least mild-to-moderate AS [aortic valve area (AVA) ≤1.5 cm² and peak jet velocity (V_Peak) ≥2.5 m/s or mean gradient (MG) ≥25 mmHg] were prospectively collected between 2005 and 2015 and retrospectively analysed. Patients with reduced left ventricular ejection fraction (mild were excluded. Among 3632 patients, 42% were women. The mean indexed AVA (0.48 ± 0.17 cm²/m²), V_Peak (3.74 ± 0.88 m/s), and MG (35.1 ± 18.2 mmHg) did not differ between sexes (all P ≥ 0.18). Women were older (72.9 ± 13.0 vs. 70.1 ± 11.8 years) and had more hypertension (75% vs. 70%; P = 0.0005) and less coronary artery disease (38% vs. 55%, P < 0.0001) compared to men. After inverse-propensity weighting (IPW), female sex was associated with higher mortality (IPW-HR: 1.91 [1.14–3.22]; P = 0.01) and less referral to valve intervention (competitive model IPW-HR: 0.88 [0.82–0.96]; P = 0.007) in the whole cohort. This excess mortality in women was blunted in concordant non-severe AS initially treated conservatively (IPW-HR = 1.03 [0.63–1.68]; P = 0.88) or in concordant severe AS initially treated by valve intervention (IPW-HR = 1.25 [0.71–2.21]; P = 0.43). Interestingly, the excess mortality in women was observed in discordant low-gradient AS patients (IPW-HR = 2.17 [1.19–3.95]; P = 0.01) where women were less referred to valve intervention (IPW-Sub-HR: 0.83 [0.73–0.95]; P = 0.009). In this large series of patients, despite similar baseline hemodynamic AS severity, women were less referred to AVR and had higher mortality. This seemed mostly to occur in the patient subset with discordant markers of AS severity (i.e. low-gradient AS) where women were less referred to AVR. Compared to men, women with low-gradient aortic stenosis have a worse survival, which could be partly explained by a lower rate of aortic valve replacement in women. IPW-HR, inverse-probability weighted hazard ratio.

Background: Early vascular aging (EVA) is associated with higher risk of adverse cardiovascular events and can be estimated noninvasively by assessing arterial hemodynamics. Women with a history of preeclampsia have increased risk of cardiovascular disease, but underlying mechanisms are incompletely understood. We hypothesized that women with a history of preeclampsia display persistent arterial abnormalities and EVA in the postpartum period. Methods and Results: We performed a comprehensive, noninvasive arterial hemodynamic evaluation in women with a history of preeclampsia (n=40) and age‐matched controls with previous normotensive pregnancies (n=40). We used validated methods integrating applanation tonometry with transthoracic echocardiography to obtain measures of aortic stiffness, steady and pulsatile arterial load, central blood pressure, and arterial wave reflections. Presence of EVA was defined as aortic stiffness higher than that predicted from reference values based on the participant's age and blood pressure. The association of preeclampsia with arterial hemodynamic variables was assessed with multivariable linear regression, and the association of severe preeclampsia with EVA was assessed with multivariable logistic regression, adjusted for confounders. We found that women with a history of preeclampsia had greater aortic stiffness, steady arterial load, central blood pressure, and arterial wave reflections when compared with controls. We observed a dose–response relationship, with the greatest abnormalities observed in subgroups with severe, preterm, or recurrent preeclampsia. Women with severe preeclampsia had 9.23 times greater odds of having EVA as compared with controls (95% CI, 1.67–51.06, P =0.011) and 7.87 greater odds of EVA as compared with women with nonsevere preeclampsia (95% CI, 1.29–47.77, P =0.025). Conclusions: Our study comprehensively characterizes arterial hemodynamic abnormalities after preeclampsia and suggests that specific subgroups of women with a history of preeclampsia exhibit greater alterations in arterial hemodynamics related to arterial health. Our findings have important implications for understanding potential links between preeclampsia and cardiovascular events, and suggest women with severe, preterm, or recurrent preeclampsia as subgroups who may deserve intensification of efforts for prevention and early detection of cardiovascular disease.

Purpose of review: Coronary artery bypass graft (CABG) surgery remains the gold-standard treatment for multivessel and left main coronary artery disease. Despite significant improvement in cardiovascular outcomes, patients undergoing CABG remain at risk for recurrent adverse ischemic events and other cardiovascular outcomes (coronary revascularisation, stroke, cardiac death, etc.). The purpose of this review is to summarize the most recent evidence in pharmacological preventive therapies addressing the residual cardiovascular risk in patients who have undergone CABG. Recent findings: Novel cardiovascular pharmacological preventive strategies targeting inflammatory, metabolic and prothrombotic (antiplatelet and anticoagulation) pathways have been recently assessed, with promising results for secondary prevention after CABG. Summary: Secondary prevention is an essential part of postoperative care after CABG. Novel lipid-lowering and glucose-controlling agents suggest a strong and consistent benefit on native coronary artery disease and overall cardiovascular outcomes. The role and the choice of enhanced antiplatelet/anticoagulation/lipid/glucose-modulating therapies following CABG should be better defined and deserves further investigation. Additional studies are required to identify new therapeutic target addressing the specific multifactorial nature of the graft CV disease and identifying the best preventive strategies for long-term graft patency.

Background: Myocardial infarction (MI) has been shown to induce fibrotic remodelling of the mitral and tricuspid valves. It is unknown whether MI also induces pathological remodelling of the aortic valve and alters aortic stenosis (AS) progression. We thus compared AS progression after an acute MI and in patients with/without history of MI, and assessed post-MI pathobiological changes within the aortic valve leaflets in a sheep model. Methods: Serial echocardiograms in human patients with AS were retrospectively analysed and compared between 3 groups: (1) acute MI at baseline (n=68), (2) prior history of MI (n=45) and (3) controls without MI (n=101). Annualised progression rates of AS severity were compared between these 3 groups. In addition, aortic valves were harvested from 15 sheep: (1) induced inferior MI (n=10) and (2) controls without MI (n=5), for biological and histological analyses. Results: In humans, the acute MI, previous MI and control groups had comparable baseline AS severity. Indexed aortic valve area (AVA_i) declined faster in the acute MI group compared with controls (−0.07±0.06 vs −0.04±0.04 cm²/m²/year; p=0.004). After adjustment, acute MI status was significantly associated with faster AVA_i progression (mean difference: −0.013 (95% CI −0.023 to −0.003) cm²/m²/year, p=0.008). In the post-MI experimental animal model, aortic valve thickness and qualitative/quantitative expression of collagen were significantly increased compared with controls. Conclusions: The results of this study suggest that AS progression is accelerated following acute MI, which could be caused by increased collagen production and thickening of the aortic valve after the ischaemic event.

Introduction: There 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. Methods: We 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. Results: Mean 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. Conclusion: In 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.