Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol- or Apolipoprotein B-Related Risk of Coronary Heart Disease.

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 (LDL _Lp(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 LDL _Lp(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 LDL _Lp(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-C _Lp(a)corr30 or LDL-C _{Lp(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; P _interaction 0.39). 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]) (P _interaction 0.49).
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.
Competing Interests: Funding Support and Author Disclosures The BiomarCaRE Project is funded by the European Union Seventh Framework Programme Collaborative Project (FP7/2007–2013) under grant agreement no. HEALTHF2-2011–278913. The MORGAM Project has received funding from European Union projects MORGAM (Biomed, BMH4-CT98-3183), GenomEUtwin (Fifth Framework Programme FP5, QLG2-CT-2002-01254), BiomarCaRE (FP7, HEALTH-F2-2011-278913), European Network for Genetic and Genomic Epidemiology (ENGAGE) (FP7, HEALTH-F4-2007-201413), Consortium on Health and Ageing: Network of cohorts in Europe and the United States (CHANCES) (FP7, HEALTH-F3-2010-242244), euCanSHare (Horizon 2020, No. 825903), Digital, Risk-Based Screening for Atrial Fibrillation in the European Community project - European Union (AFFECT-EU) (Horizon 2020, no. 847770), and Medical Research Council, London (G0601463, no. 80983: Biomarkers in the MORGAM Populations). This funding has supported central coordination, workshops, and part of the activities of the MORGAM Data Centre, the MORGAM Laboratories, and the MORGAM Participating Centres; MORGAM Participating Centres are funded by regional and national governments, research councils, charities, and other local sources. Dr Schnabel has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 648131), German Ministry of Research and Education (BMBF 01ZX1408A), and German Center for Cardiovascular Research (DZHK e.V.; grant no. 81Z1710103); and has received personal fees from BMS/Pfizer. Dr Kee has received funding from the National Institute of Health Research United Kingdom. Dr Salomaa was supported by the Finnish Foundation for Cardiovascular Research and the Juho Vainio Foundation; and has received grants from Bayer AG. Dr Zeller was supported by the German Center of Cardiovascular Research (DZHK e.V.; DZHK, 81Z0710102). Dr Blankenberg has received a grant from Abbott Diagnostics during the conduct of the study; has received grants and personal fees from Abbott Diagnostics, Bayer, SIEMENS, and Thermo Fisher; has received grants from Singulex; and has received personal fees from AstraZeneca, AMGEN, Medtronic, Pfizer, Roche, Siemens Diagnostic, and Novartis. Dr Söderberg has been supported by the Swedish Heart-Lung Foundation (20140799, 20120631, and 20100635), the County Council of Västerbotten (ALF, VLL- RV-967561, RV-841381548791), and Umeå University; and has received grants and personal fees from Actelion Ltd. All funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Outside the scope of the present work, Dr Arnold has received consulting fees and grant support from Novartis. Dr Brunner has received grant supports from Daiichi-Sankyo, Novartis, Pfizer, and Sanofi; has received nonfinancial support from Abbott, ASAHI INTECC, and Inari Medical; and has received personal fees from Amgen and Novartis. Dr Bay is supported by a grant from the German Heart Foundation (grant no. S/06/23). Dr Koenig has received consulting fees and lecture fees from AstraZeneca, Novartis, and Amgen; has received consulting fees from Pfizer, The Medicines Company, DalCor Pharmaceuticals, Kowa, Corvidia Therapeutics, Esperion, Genentech, OMEICOS, Novo Nordisk, LIB Therapeutics, TenSixteen Bio, New Amsterdam Pharma, and Daiichi-Sankyo; has received lecture fees from Berlin-Chemie, Bristol Myers Squibb, and Sanofi; and has received grant support and provision of reagents from Singulex, Abbott, Roche Diagnostics, and Dr Beckmann Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)