Elevated OxPL-apoB is significantly associated with prevalent aortic valve calcium (OR 1.19 per SD) and faster progression of established aortic stenosis, particularly in the setting of elevated Lp(a) levels.
Cohort (n=5,576)
Yes
Odds Ratio: 1.19 (95% CI 1.07–1.32)
BACKGROUND Oxidized phospholipids (OxPLs) are carried by apolipoprotein B-100–containing lipoproteins (OxPL-apoB) including lipoprotein(a) (Lpa). Both OxPL-apoB and Lp(a) have been associated with calcific aortic valve disease (CAVD). OBJECTIVES This study aimed to evaluate the associations between OxPL-apoB, Lp(a) and the prevalence, incidence, and progression of CAVD. METHODS OxPL-apoB and Lp(a) were evaluated in MESA (Multi-Ethnic Study of Atherosclerosis) and a participant-level meta-analysis of 4 randomized trials of participants with established aortic stenosis (AS). In MESA, the association of OxPL-apoB and Lp(a) with aortic valve calcium (AVC) at baseline and 9.5 years was evaluated using multivariable ordinal regression models. In the meta-analysis, the association between OxPL-apoB and Lp(a) with AS progression (annualized change in peak aortic valve jet velocity) was evaluated using multivariable linear regression models. RESULTS In MESA, both OxPL-apoB and Lp(a) were associated with prevalent AVC (OR per SD: 1.19 95% CI: 1.07–1.32 and 1.13 95% CI: 1.01–1.27, respectively) with a significant interaction between the two (P < 0.01). Both OxPL-apoB and Lp(a) were associated with incident AVC at 9.5 years when evaluated individually (interaction P < 0.01). The OxPL-apoB*Lp(a) interaction demonstrated higher odds of prevalent and incident AVC for OxPL-apoB with increasing Lp(a) levels. In the meta-analysis, when analyzed separately, both OxPL-apoB and Lp(a) were associated with faster increase in peak aortic valve jet velocity, but when evaluated together, only OxPL-apoB remained significant (ß: 0.07; 95% CI: 0.01–0.12). CONCLUSIONS OxPL-apoB is a predictor of the presence, incidence, and progression of AVC and established AS, particularly in the setting of elevated Lp(a) levels, and may represent a novel therapeutic target for CAVD.
“This is really exciting because we might have one therapy that's addressing both ASCVD risk associated with Lp(a) as well as potentially the first medical therapy for aortic stenosis.”
Bhatia et al. (2024) conducted a cohort in Calcific Aortic Valvular Disease (n=5,576). Oxidized phospholipids on apolipoprotein B (OxPL-apoB) vs. Lower levels of OxPL-apoB was evaluated on Prevalent aortic valve calcium (AVC) (OR 1.19, 95% CI 1.07-1.32). Elevated OxPL-apoB is significantly associated with prevalent aortic valve calcium (OR 1.19 per SD) and faster progression of established aortic stenosis, particularly in the setting of elevated Lp(a) levels.