A large population-based cohort study published in the European Journal of Preventive Cardiology reported that apolipoprotein B (apoB)-containing lipid markers and lipoprotein(a) [Lp(a)] were independently associated with incident AS, with additional sex-specific effects observed for Lp(a).

The analysis included 365,771 participants from the UK Biobank without baseline cardiovascular disease. The cohort had a mean age of 56.1±8.07 years, and 55.74% were women. Routine lipid traits underwent hierarchical clustering, and sex-stratified Cox proportional hazards models were used to evaluate associations with incident AS and aortic regurgitation (AR). Discordance analyses and time-dependent concordance index assessments compared the predictive performance of different lipid markers.

Hierarchical clustering identified three lipid clusters in both sexes, including an apoB-containing cluster and an apolipoprotein A-containing cluster, while Lp(a) formed an independent branch. During a median follow-up of 13.8 years, 3118 incident AS cases and 1239 AR cases were documented.

Total cholesterol, apoB, low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein cholesterol, and Lp(a) were independently associated with increased AS risk in both sexes (all P<0.01). Lp(a) demonstrated an additional sex-specific association with AS risk (P for interaction=0.004). Discordance analyses showed apoB had a stronger association with AS than LDL-c. Combining Lp(a) with apoB or LDL-c improved AS risk prediction, particularly in men. No lipid biomarker was associated with AR.
The findings identified apoB and Lp(a) as important markers associated with incident AS risk.

The analysis also demonstrated sex-specific differences in the association between Lp(a) and AS risk.