Mitral Annular Calcification as a Marker of the HFpEF Phenotype: The Interplay of Cardiac Remodeling, Age, and Sex.

Mitral annular calcification (MAC) is recognized as a marker of cardiovascular risk. However, the structural and hemodynamic predictors of its presence and severity remain insufficiently defined. We analyzed a large, consecutive cohort of 49,093 individuals undergoing echocardiography at our tertiary medical center, classifying them into three groups: normal annulus (79.5%), MAC (17.3%), or severe MAC (3.2%). Clinical and echocardiographic multivariable logistic regression models were used to identify independent predictors of MAC presence and severity. Age was a significant predictor of MAC and was characterized by a marked age-by-sex interaction, with the prevalence diverging after age 60. Severe MAC was twice as frequent in women aged ≥70 years. Diabetes, hypertension, renal dysfunction, obesity and heart failure with preserved ejection fraction (HFPEF) were significant independent predictors of MAC. After incorporation of structural variables, concentric remodeling and diastolic parameters emerged as significant determinants. Increased absolute and relative wall thickness, smaller left ventricular end diastolic dimension (LVEDD), higher E/e', left atrial enlargement, and elevated pulmonary pressures were significant predictors of the presence of MAC. Among individuals with MAC, severity was associated with age, sex, diabetes, HFPEF, smaller LVEDD, and elevated filling pressures. During 1,786 days of median follow-up, MAC was an independent predictor of mortality (severe MAC: HR 1.29, 95% CI 1.12-1.48, p<0.001). In conclusion, MAC is age and sex-related and is significantly associated with structural features of a diastolic impairment profile. Severe MAC serves as an indicator of cardiac remodeling and may warrant focused management of diastolic dysfunction and systemic metabolic risk.