Graded Severity of Aortic Valve Sclerosis as an Independent Clinical Marker of Systemic Disease, Diastolic Dysfunction, and Mortality Risk: A Large Echocardiographic Cohort Study

Background: Aortic valve sclerosis (AVS) is highly prevalent in the elderly. However, the prognostic implications of different degrees of echocardiographic AVS severity, and its association with comorbidities, myocardial remodeling, and heart failure phenotypes remains incompletely defined. Methods: We studied 42,959 participants from a large institutional echocardiographic database. AVS severity was classified as Normal (69%), Thickened (16%), Calcified (13%), or Severely Calcified (2%). Subjects with aortic stenosis greater than mild were excluded. Results: Increasing AVS severity was consistently associated with a higher burden of systemic comorbidities: hypertension, diabetes mellitus, atherosclerotic cardiovascular disease, heart failure, atrial fibrillation and renal disease. It was also associated with concentric left ventricular (LV) geometry, reflected by increased relative wall thickness and LV mass index. Worsening diastolic dysfunction was evident with increasing degrees of AVS, including reduced mitral annular e′ velocity, an elevated E/e′ ratio, increased left atrial volume index, and higher tricuspid regurgitation gradient. A rising prevalence of clinical heart failure with preserved ejection fraction (HFpEF) was observed. After multivariable adjustment including diastolic parameters, AVS severity demonstrated a strong, dose-dependent, independent association with all-cause mortality. Patients with severe calcification demonstrated the highest risk, with a hazard increase exceeding 60%. AVS severity was also a predictor of the composite endpoint of death and cardiovascular hospitalization. Conclusions: AVS severity assessed on echocardiography demonstrates strong, dose‑dependent associations with systemic comorbidities, concentric LV geometry, and HFpEF, and carries substantial prognostic significance. These findings highlight the clinical relevance of AVS severity as an early stage of the aortic valve disease spectrum, underscoring the need for proactive management of the systemic disease continuum.