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Arnold, N.* ; Blaum, C.* ; Goßling, A.* ; Brunner, F.J.* ; Bay, B.* ; Zeller, T.* ; Ferrario, M.M.* ; Brambilla, P.* ; Cesana, G.* ; Leoni, V.* ; Palmieri, L.* ; Donfrancesco, C.* ; Ojeda, F.* ; Linneberg, A.* ; Söderberg, S.* ; Iacoviello, L.* ; Gianfagna, F.* ; Costanzo, S.* ; Sans, S.* ; Veronesi, G.* ; Thorand, B. ; Peters, A. ; Tunstall-Pedoe, H.* ; Kee, F.* ; Salomaa, V.* ; Schnabel, R.B.* ; Kuulasmaa, K.* ; Blankenberg, S.* ; Waldeyer, C.* ; Koenig, W.*

Impact of lipoprotein(a) level on low-density lipoprotein cholesterol– or apolipoprotein B–related risk of coronary heart disease.

J. Am. Coll. Cardiol. 84, 165-177 (2024)
DOI PMC
Open Access Green: Postprint online available 07/2025
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Apolipoprotein B ; Coronary Heart Disease ; General Population ; Lipoprotein(a) ; Low-density Lipoprotein; Oxidized Phospholipids; Ldl-c; Plasma
ISSN (print) / ISBN 0735-1097
e-ISSN 1558-3597
Quellenangaben Volume: 84, Issue: 2, Pages: 165-177 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Grants Bristol Myers Squibb
Berlin-Chemie
LIB Therapeutics
Genentech
Esperion
Kowa
Medicines Company