Key result
Elevated apoB driven by high remnant cholesterol is linked to ~45% greater ASCVD risk.
Why the study?
Lipid-lowering therapy is typically initiated for high LDL cholesterol marked by elevated apoB, but whether elevated apoB due to high remnant cholesterol confers equal ASCVD risk with less treatment initiation was unknown.
Does elevated apoB due to high remnant cholesterol confer a higher risk of ASCVD and lower initiation of lipid-lowering therapy compared to elevated apoB due to high LDL cholesterol in primary prevention?
Cohort (n=94,299)
Does elevated apoB due to high remnant cholesterol confer a higher risk of ASCVD and lower initiation of lipid-lowering therapy compared to elevated apoB due to high LDL cholesterol in primary prevention?
Effect estimate: HR 1.45 (95% CI 1.34-1.56)
Elevated apoB driven by high remnant cholesterol confers a higher ASCVD risk but prompts less lipid-lowering therapy initiation than elevated apoB driven by high LDL cholesterol, identifying a critical gap in primary prevention guidelines.
Remnant cholesterol-driven apoB elevation was associated with higher ASCVD risk yet lower therapy initiation; leaves open remnant-targeted strategies in primary prevention.
AIMS: Lipid-lowering therapy is typically initiated at high low-density lipoprotein(LDL) cholesterol marked by elevated apolipoprotein B(apoB). We tested the hypothesis that elevated apoB alternatively due to high remnant cholesterol confers equally high risk of atherosclerotic cardiovascular disease(ASCVD) but less initiation of lipid-lowering therapy, compared to elevated apoB due to high LDL cholesterol. METHODS AND RESULTS: From the Copenhagen General Population Study, 94 299 lipid-lowering therapy naïve adults without a history of ASCVD were included in 2003-2015. Discordance groups were formed by median levels of remnant cholesterol, LDL cholesterol and apoB. In the national Danish health registries, individuals were followed for a prescription of lipid-lowering therapy and for incident ASCVD until December 2021. During a median follow-up of 12 years, 9269 developed ASCVD. Compared to individuals with concordant low values of remnant cholesterol, apoB, and LDL cholesterol, those with high remnant cholesterol and high apoB but low LDL cholesterol had a hazard ratio(HR) of 1.45 (95% confidence interval: 1.34-1.56) for ASCVD and an odds ratio(OR) of 3.0 (2.5-3.6) for starting lipid-lowering therapy within one year. Correspondingly, those with low remnant cholesterol but high apoB and high LDL cholesterol had a HR of 1.20 (1.11-1.30) for ASCVD and an OR of 5.1 (4.3-5.9) for starting lipid-lowering therapy. CONCLUSION: In a primary prevention setting, elevated apoB due to high remnant cholesterol confers high risk of ASCVD but less initiation of lipid-lowering therapy compared to elevated apoB due to high LDL cholesterol, representing a guideline-based limitation and an unmet medical need.
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Hvid et al. (2025) conducted a cohort in Primary prevention of ASCVD (n=94,299). High remnant cholesterol and high apoB but low LDL cholesterol vs. Concordant low values of remnant cholesterol, apoB, and LDL cholesterol was evaluated on Incident ASCVD (HR 1.45, 95% CI 1.34-1.56). Elevated apoB driven by high remnant cholesterol increased ASCVD risk compared to concordant low lipid levels (HR 1.45; 95% CI 1.34-1.56) but prompted less lipid-lowering therapy initiation.
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