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

BiomarCaRE investigators, Natalie Arnold, Christopher Blaum, Alina Goßling, Fabian J. Brunner, Benjamin Bay, Tanja Zeller, Marco M. Ferrario, Paolo Brambilla, Giancarlo Cesana, Valerio Leoni, Luigi Palmieri, Chiara Donfrancesco, Francisco Ojeda, Allan Linneberg, Stefan Söderberg, Licia Iacoviello, Francesco Gianfagna, Simona Costanzo, Susana SansGiovanni Veronesi, Barbara Thorand, Annette Peters, Hugh Tunstall-Pedoe, Frank Kee, Veikko Salomaa, Renate B. Schnabel, Kari Kuulasmaa, Stefan Blankenberg, Christoph Waldeyer, Wolfgang Koenig

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)165-177
Number of pages13
JournalJournal of the American College of Cardiology
Volume84
Issue number2
DOIs
Publication statusPublished - 9 Jul 2024

Keywords

  • apolipoprotein B
  • coronary heart disease
  • general population
  • lipoprotein(a)
  • low-density lipoprotein

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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