Genetics
In 68,748 subjects, correcting LDL-C for its Lp(a) cholesterol content adds nothing at the population level, but Lp(a) mass changes what apoB and LDL-C mean for individual risk (J Am Coll Cardiol 2024)
Original title: Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol- or Apolipoprotein B-Related Risk of Coronary Heart Disease
Among 68,748 coronary heart disease (CHD)-free subjects, this study compared standard LDL-C against LDL-C corrected for its Lp(a)-cholesterol content (subtracting 30% or 17.3% of total Lp(a) mass) for predicting incident CHD, and tested whether Lp(a) mass modifies the LDL-C or apolipoprotein B (apoB) risk relationship. Risk estimates for incident CHD were similar for uncorrected LDL-C and both corrected versions (subdistribution hazard ratios 2.73, 2.51, and 2.64 respectively, top versus bottom fifth). However, stratifying by Lp(a) mass (90th percentile or above versus below) showed uncorrected LDL-C carried a much higher hazard ratio for incident CHD in the high-Lp(a) group (4.38) than the low-Lp(a) group (2.60), while the apoB hazard ratio was lower in the high-Lp(a) group (2.43) than the low-Lp(a) group (3.34). Correcting LDL-C for its Lp(a) content provides no meaningful population-level improvement in CHD risk prediction, but simply knowing whether a patient's Lp(a) mass is high or low changes how LDL-C and apoB should be interpreted for individual risk.
Original abstract
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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.