Why the study?
Conventional LDL-C quantification includes lipoprotein(a) cholesterol due to overlapping densities. How correcting LDL-C for Lp(a)-C compares with conventional LDL-C for incident CHD risk, and whether Lp(a) levels influence LDL-C or apoB associations with coronary events, needed investigation.
Does correcting LDL-C for Lp(a)-C content or stratifying by Lp(a) mass alter the estimated risk of incident coronary heart disease associated with LDL-C or apolipoprotein B in a CHD-free general population?
Cohort (n=68,748)
Does correcting LDL-C for Lp(a)-C content or stratifying by Lp(a) mass alter the estimated risk of incident coronary heart disease associated with LDL-C or apolipoprotein B in a CHD-free general population?
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Lp(a) levels may add information on CHD-related risk for some groups. However, data from this large cohort did not observe the added value of Lp(a) when examining LDL or apoB in association with CHD risk in a general population.”
Routine mathematical correction of LDL-C for its Lp(a)-C content does not meaningfully improve population-level coronary heart disease risk estimation compared with standard LDL-C.
BACKGROUND Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities. OBJECTIVES The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events. METHODS Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile). RESULTS Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49). CONCLUSIONS Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.
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Arnold et al. (2024) conducted a cohort in Primary prevention of coronary heart disease (CHD-free general population) (n=68,748). LDL-C corrected for Lp(a)-C (assuming Lp(a)-C is 30% or 17.3% of total Lp(a) mass) and stratification by Lp(a) mass (≥/<90th percentile) vs. Conventional uncorrected LDL-C and apolipoprotein B (top vs bottom fifth) was evaluated on Incident coronary heart disease (CHD) (HR 2.51, 95% CI 2.15-2.93).
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