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

• Published in: Journal of the American College of Cardiology Vol. 84; no. 2; pp. 165 - 177
• Main Authors: Arnold, Natalie, MD, Blaum, Christopher, MD, Goßling, Alina, MSc, Brunner, Fabian J., MD, Bay, Benjamin, MD, Zeller, Tanja, PhD, Ferrario, Marco M., MD, PhD, Brambilla, Paolo, MD, Cesana, Giancarlo, PhD, Leoni, Valerio, MD, Palmieri, Luigi, PhD, Donfrancesco, Chiara, PhD, Ojeda, Francisco, PhD, Linneberg, Allan, MD, Söderberg, Stefan, MD, Iacoviello, Licia, MD, PhD, Gianfagna, Francesco, MD, Costanzo, Simona, PhD, Sans, Susana, MD, PhD, Veronesi, Giovanni, PhD, Thorand, Barbara, PhD, Peters, Annette, PhD, Tunstall-Pedoe, Hugh, MD, Kee, Frank, MD, Salomaa, Veikko, MD, Schnabel, Renate B., MD, Kuulasmaa, Kari, PhD, Blankenberg, Stefan, MD, Waldeyer, Christoph, MD, Koenig, Wolfgang, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.07.2024
• Subjects: Adult; Aged; apolipoprotein B; Apolipoproteins B - blood; Cardiovascular; Cholesterol, LDL - blood; Coronary Disease - blood; Coronary Disease - epidemiology; coronary heart disease; Female; general population; Humans; Incidence; lipoprotein(a); Lipoprotein(a) - blood; low-density lipoprotein; Male; Middle Aged; Risk Assessment - methods; Risk Factors; ASCVD; LDL-C; low-density lipoprotein cholesterol; myocardial infarction; atherosclerotic cardiovascular disease; general population; subdistribution HR; Lp(a); low-density lipoprotein; apoB; HDL-C; oxPL; LDL; high-density lipoprotein cholesterol; coronary heart disease; MI; sHR; apolipoprotein B; lipoprotein(a); CHD; oxidized phospholipid
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2024.04.050

AbstractBackgroundConventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities. ObjectivesThe 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. MethodsAmong 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). ResultsSimilar 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; 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). ConclusionsCorrection 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.