Article, 2024

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

Journal of the American College of Cardiology, ISSN 1558-3597, 0735-1097, Volume 84, 2, Pages 165-177, 10.1016/j.jacc.2024.04.050

Contributors

Arnold, Natalie 0000-0002-0809-8108 [1] [2] Blaum, Christopher M 0000-0002-7414-2162 [1] Goßling, Alina 0000-0002-5211-5593 [1] Brunner, Fabian Johannes [1] [2] Bay, Benjamin 0000-0002-4927-8033 [1] [2] Zeller, T Aaron 0000-0003-3379-2641 [1] [2] Ferrario, Marco M. [3] Brambilla, Paolo [4] Cesana, Gian Carlo 0000-0003-2728-2485 [4] Leoni, Valerio 0000-0002-8954-0366 [4] Palmieri, Luigi [5] Donfrancesco, Chiara 0000-0002-8040-5571 [5] Ojeda, Francisco [1] Linneberg, Allan 0000-0002-0994-0184 [6] [7] Söderberg, Stefan [8] Iacoviello, Licia 0000-0003-0514-5885 [9] [10] Gianfagna, Francesco 0000-0003-4615-0816 [3] [11] Costanzo, Simona 0000-0003-4569-1186 [9] Sans, Susana [12] Veronesi, Giovanni [3] Thorand, Barbara 0000-0002-8416-6440 [13] [14] Peters, Annette 0000-0001-6645-0985 [2] [13] [14] Tunstall-Pedoe, Hugh D [15] Kee, Frank [16] Salomaa, Veikko [17] Schnabel, Renate B 0000-0001-7170-9509 [1] [2] Kuulasmaa, Kari Antero 0000-0003-2165-1411 [17] Blankenberg, Stefan 0000-0001-6488-2362 [1] [2] Waldeyer, Christoph [1] [2] Koenig, Wolfgang 0000-0002-2064-9603 (Corresponding author) [2] [18] [19] Investigators, Biomarcare [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]

Affiliations

  1. [1] University Medical Center Hamburg-Eppendorf
    2. [NORA names: Germany; Europe, EU; OECD];
  2. [2] German Centre for Cardiovascular Research
    3. [NORA names: Germany; Europe, EU; OECD];
  3. [3] University of Insubria
    4. [NORA names: Italy; Europe, EU; OECD];
  4. [4] University of Milano-Bicocca
    5. [NORA names: Italy; Europe, EU; OECD];
  5. [5] Istituto Superiore di Sanità
    6. [NORA names: Italy; Europe, EU; OECD];

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.

Keywords

CHD risk estimates, CHD-free subjects, Gray, HR, LDL, LDL-C, Lp(a, Lp(a) mass, Lp(a)-C, apoB, apolipoprotein, apolipoprotein B, association, association of LDL-C, baseline, categorization, cholesterol, content, coronary events, coronary heart disease, correction, density, disease, estimation, events, general population, heart disease, impact, incident coronary heart disease, information, levels, lipoprotein cholesterol, lipoprotein(a, low-density, low-density lipoprotein cholesterol, mass, model, outcomes, percentile, population, population level, quantification, risk, risk estimates, risk of coronary heart disease, risk-adjustment models, samples, stratification, study, subdistribution, subdistribution HR, subjects

Funders

  • European Research Council
  • Juho Vainio Foundation
  • German Centre for Cardiovascular Research
  • Swedish Heart-Lung Foundation
  • National Institute for Health and Care Research
  • Federal Ministry of Education and Research
  • Finnish Foundation for Cardiovascular Research
  • Medical Research Council
  • Novo Nordisk (Denmark)
  • European Commission
  • Västerbottens Läns Landsting

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