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

TY - JOUR

T1 - Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol– or Apolipoprotein B–Related Risk of Coronary Heart Disease

AU - BiomarCaRE investigators

AU - Arnold, Natalie

AU - Blaum, Christopher

AU - Goßling, Alina

AU - Brunner, Fabian J.

AU - Bay, Benjamin

AU - Zeller, Tanja

AU - Ferrario, Marco M.

AU - Brambilla, Paolo

AU - Cesana, Giancarlo

AU - Leoni, Valerio

AU - Palmieri, Luigi

AU - Donfrancesco, Chiara

AU - Ojeda, Francisco

AU - Linneberg, Allan

AU - Söderberg, Stefan

AU - Iacoviello, Licia

AU - Gianfagna, Francesco

AU - Costanzo, Simona

AU - Sans, Susana

AU - Veronesi, Giovanni

AU - Thorand, Barbara

AU - Peters, Annette

AU - Tunstall-Pedoe, Hugh

AU - Kee, Frank

AU - Salomaa, Veikko

AU - Schnabel, Renate B.

AU - Kuulasmaa, Kari

AU - Blankenberg, Stefan

AU - Waldeyer, Christoph

AU - Koenig, Wolfgang

N1 - Publisher Copyright: © 2024 American College of Cardiology Foundation

PY - 2024/7/9

Y1 - 2024/7/9

N2 - 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.

AB - 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.

KW - apolipoprotein B

KW - coronary heart disease

KW - general population

KW - lipoprotein(a)

KW - low-density lipoprotein

U2 - 10.1016/j.jacc.2024.04.050

DO - 10.1016/j.jacc.2024.04.050

M3 - Article

C2 - 38960510

AN - SCOPUS:85196710068

SN - 0735-1097

VL - 84

SP - 165

EP - 177

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 2

ER -