Aortic sclerosis

Definition. Aortic sclerosis is focal thickening, fibrosis and calcification of the aortic valve leaflets WITHOUT significant obstruction to left ventricular outflow — by convention a peak transvalvular velocity below 2.5 m/s with normal leaflet excursion. It is the earliest, non-obstructive stage of the same disease process that culminates in calcific degenerative aortic stenosis.

Prevalence. It is very common. Aortic valve cusp sclerosis or calcification is present in 26% of adults older than 65, and in the Cardiovascular Health Study the prevalence was 29% of the elderly, rising to about 40–50% of those over 80. Roughly 10–15% progress to haemodynamically significant aortic stenosis over 5–10 years, at an average rate of about 1–2% per year.

Pathogenesis — an atherosclerosis-like process. Degenerative aortic valve disease was for many years thought to result from the passive accumulation of calcium on the surface of the valve leaflet; it is now established that its aetiology has a pathophysiology similar to that of vascular atherosclerosis. Early stages resemble active atherosclerotic inflammation — basement membrane disruption, lipid deposition, inflammatory cell infiltration and calcification, with later osteoblastic differentiation of valve interstitial cells. Shared risk factors — age, male sex, smoking, hypertension, diabetes, dyslipidaemia (particularly raised Lp(a)), chronic kidney disease and visceral obesity — give rise to the concept of valvulo-metabolic risk. Note that only about 50% of patients with degenerative aortic valve disease have significant coronary disease, and most patients with coronary disease do not have valve disease, so additional factors must be involved.

Clinical features. Aortic sclerosis is asymptomatic by definition and is usually found incidentally. The sign is an ejection systolic murmur, loudest at the aortic area, typically early-peaking, short and grade 1–2/6, and crucially it is accompanied by a normal carotid upstroke, a normal pulse pressure and a normally preserved (often accentuated) aortic component of the second heart sound. There is no left ventricular hypertrophy attributable to the valve.

Distinguishing sclerosis from stenosis. This is the crux of the answer, and it can be difficult in older adults on clinical grounds alone.

Prognostic significance and management. Aortic sclerosis is NOT a benign incidental finding: it is associated with an increase in the risk of death from cardiovascular causes and the risk of myocardial infarction, even in the absence of haemodynamically significant obstruction of left ventricular outflow — an approximately 50% relative increase in cardiovascular death and myocardial infarction in the Cardiovascular Health Study. It should therefore be treated as a marker of systemic atherosclerotic burden and a trigger for comprehensive cardiovascular risk assessment: assess and treat blood pressure, lipids, diabetes, smoking, weight and renal function. No treatment retards progression of the valve lesion itself — statins have been shown not to slow progression despite the atherosclerotic pathogenesis, since 60–70% of patients with degenerative valve disease are already dyslipidaemic and on statins yet still progress rapidly, suggesting that targeting the entire metabolic risk rather than lipids alone may be more effective. Management is therefore risk factor modification plus surveillance: repeat echocardiography every 3–5 years, or sooner if symptoms develop or the murmur changes. Antibiotic prophylaxis for infective endocarditis is not recommended for aortic sclerosis.

Lipoprotein(a) has emerged as the strongest causal lipid driver of calcific aortic valve disease, and it is the one modifiable factor that distinguishes valve disease from ordinary atherosclerosis. Mendelian randomisation and cohort data show that elevated Lp(a) and the LPA risk genotype are causally associated with aortic valve calcification, incident aortic stenosis and faster progression from sclerosis to stenosis — which explains why statins, which do not lower Lp(a), have repeatedly failed to slow valve disease. Current ESC/EAS and 2025 AHA/ACC guidance recommends measuring Lp(a) at least once in every adult, and Lp(a)-lowering agents (pelacarsen in Lp(a)HORIZON, olpasiran, lepodisiran) are in phase 3 trials, offering the first prospect of disease-modifying therapy for calcific aortic valve disease.