Age, Sex, and Valve Phenotype Differences in Fibro‐Calcific Remodeling of Calcified Aortic Valve

Abstract

Background In calcific aortic valve disease on tricuspid aortic valves ( TAVs ), men have higher aortic valve calcification and less fibrosis than women. However, little is known in bicuspid aortic valves ( BAV ). We thus aimed to investigate the impact of age, sex, and valve phenotype ( TAVs versus BAVs ) on fibro‐calcific remodeling in calcific aortic valve disease. Methods and Results We included 2 cohorts: 411 patients who underwent multidetector computed tomography (37% women) for aortic valve calcification density assessment and 138 explanted aortic valves (histological cohort; 50% women). The cohorts were divided in younger (<60 years old) or older patients with BAV (≥60 years old), and TAV patients. In each group, women and men were matched. Women presented less aortic valve calcification density than men in each group of the multidetector computed tomography cohort (all P ≤0.01). Moreover, in women, younger patients with BAV had the lowest aortic valve calcification density (both P =0.02). In multivariate analysis, aortic valve calcification density correlated with age (β estimate±standard error: 6.5±1.8; P =0.0004) and male sex (109.2±18.4; P <0.0001), and there was a trend with TAVs (41.5±23.0; P =0.07). Women presented a higher collagen content than men (77.8±10.8 versus 69.9±12.9%; P <0.001) in the entire cohort. In women, younger patients with BAV had denser connective tissue than TAV and older patients with BAV (both P ≤0.05), while no difference was observed between men. Conclusions In calcific aortic valve disease, women had less calcification and more fibrotic remodeling than men, regardless of the phenotype of the valve or age of the patient. Moreover, younger women with BAVs had less valve calcification. Thus, mineralization/fibrosis of the aortic valve is likely to have sex/age‐specific mechanisms and be influenced by the valve morphology.

Changing epidemiology of calcific aortic valve disease: 30-year trends of incidence, prevalence, and deaths across 204 countries and territories

“…In a study by Tromsø, Cox proportional hazards regression was used, with age (hazard ratio 1.11, 95% CI: 1.08–1.14) identified as an independent predictor for incident CAVD [ 12 ]. Recently, a cohort study disclosed that aortic valve calcification density was related to age (β estimate±standard error: 6.5±1.8; p=0.0004) in a multivariate analysis [ 13 ]; the potential causes may include activation of the renin–angiotensin system and alteration of the phosphocalcic metabolism in older patients [ 14 – 16 ].…”

Sex-Specific Features of Calcific Aortic Valve Disease

“…To elucidate the possible differences during the progression of CAVD, several recent studies have been conducted. A recent study demonstrated that, compared to men, women with AS had more pronounced fibrotic remodeling, irrespective of the valve morphology or age of the patient [32]. The same study also showed that, in CAVD, AS hemodynamic severity may not be correlated to the degree of AVC in young women with BAV so that these women may have a hemodynamically severe AS with no or minimal AVC load.…”

Collagen fiber regulation in human pediatric aortic valve development and disease

“…Genomic studies, primarily characterized from adult end-stage phenotypes, show complex genetics with dissimilar patterns of inheritance, genetically heterogenous phenotypes, and multiple chromosomal regions that impact the ECM network directly or indirectly 45 , 47 – 49 . Gender may also play a role—while bicuspid aortic valve is three times as likely to be found in males, females have more collagen deposition and less calcification 50 , 51 . Surgical replacement of valves is an option in adults, but in children, valve replacements do not grow with the patient, leading to heart dysfunction and failure 4 , 52 .…”