Impact of lipoprotein(a) level on low-density lipoprotein cholesterol– or apolipoprotein B–related risk of coronary heart disease

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 Sans; Giovanni Veronesi; Barbara Thorand; Annette Peters; Hugh Tunstall-Pedoe; Frank Kee; Veikko Salomaa; Renate B. Schnabel; Kari Kuulasmaa; Stefan Blankenberg; Christoph Waldeyer; Wolfgang Koenig

doi:10.1016/j.jacc.2024.04.050

Impact of lipoprotein(a) level on low-density lipoprotein cholesterol– or apolipoprotein B–related risk of coronary heart disease

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 Sans
, Giovanni Veronesi

Barbara Thorand, Annette Peters, Hugh Tunstall-Pedoe, Frank Kee, Veikko Salomaa, Renate B. Schnabel, Kari Kuulasmaa, Stefan Blankenberg, Christoph Waldeyer, Wolfgang Koenig^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

22 Citations (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 language	English
Pages (from-to)	165-177
Number of pages	13
Journal	Journal of the American College of Cardiology
Volume	84
Issue number	2
Early online date	01 Jul 2024
DOIs	https://doi.org/10.1016/j.jacc.2024.04.050
Publication status	Published - 09 Jul 2024

Keywords

Adult
Aged
Apolipoproteins B - blood
Cholesterol, LDL - blood
Coronary Disease - blood - epidemiology
Female
Humans
Incidence
Lipoprotein(a) - blood
Male
Middle Aged
Risk Assessment - methods
Risk Factors
apolipoprotein B
coronary heart disease
general population
lipoprotein(a)
low-density lipoprotein

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Arnold, N., Blaum, C., Goßling, A., Brunner, F. J., Bay, B., Zeller, T., Ferrario, M. M., Brambilla, P., Cesana, G., Leoni, V., Palmieri, L., Donfrancesco, C., Ojeda, F., Linneberg, A., Söderberg, S., Iacoviello, L., Gianfagna, F., Costanzo, S., Sans, S., ... Koenig, W. (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, 84(2), 165-177. https://doi.org/10.1016/j.jacc.2024.04.050

@article{d87c57b661ab4e7ba96c0d186b2a16c8,

title = "Impact of lipoprotein(a) level on low-density lipoprotein cholesterol{\textendash} or apolipoprotein B{\textendash}related risk of coronary heart disease",

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 {\textquotedblleft}LDL-C{\textemdash}Lp(a)-C,{\textquotedblright} 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 = "Adult, Aged, Apolipoproteins B - blood, Cholesterol, LDL - blood, Coronary Disease - blood - epidemiology, Female, Humans, Incidence, Lipoprotein(a) - blood, Male, Middle Aged, Risk Assessment - methods, Risk Factors, apolipoprotein B, coronary heart disease, general population, lipoprotein(a), low-density lipoprotein",

author = "Natalie Arnold and Christopher Blaum and Alina Go{\ss}ling and Brunner, \{Fabian J.\} and Benjamin Bay and Tanja Zeller and Ferrario, \{Marco M.\} and Paolo Brambilla and Giancarlo Cesana and Valerio Leoni and Luigi Palmieri and Chiara Donfrancesco and Francisco Ojeda and Allan Linneberg and Stefan S{\"o}derberg and Licia Iacoviello and Francesco Gianfagna and Simona Costanzo and Susana Sans and Giovanni Veronesi and Barbara Thorand and Annette Peters and Hugh Tunstall-Pedoe and Frank Kee and Veikko Salomaa and Schnabel, \{Renate B.\} and Kari Kuulasmaa and Stefan Blankenberg and Christoph Waldeyer and Wolfgang Koenig",

year = "2024",

month = jul,

day = "9",

doi = "10.1016/j.jacc.2024.04.050",

language = "English",

volume = "84",

pages = "165--177",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier Inc.",

number = "2",

}

Arnold, N, Blaum, C, Goßling, A, Brunner, FJ, Bay, B, Zeller, T, Ferrario, MM, Brambilla, P, Cesana, G, Leoni, V, Palmieri, L, Donfrancesco, C, Ojeda, F, Linneberg, A, Söderberg, S, Iacoviello, L, Gianfagna, F, Costanzo, S, Sans, S, Veronesi, G, Thorand, B, Peters, A, Tunstall-Pedoe, H, Kee, F, Salomaa, V, Schnabel, RB, Kuulasmaa, K, Blankenberg, S, Waldeyer, C & Koenig, W 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, vol. 84, no. 2, pp. 165-177. https://doi.org/10.1016/j.jacc.2024.04.050

TY - JOUR

T1 - Impact of lipoprotein(a) level on low-density lipoprotein cholesterol– or apolipoprotein B–related risk of coronary heart disease

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

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 - Adult

KW - Aged

KW - Apolipoproteins B - blood

KW - Cholesterol, LDL - blood

KW - Coronary Disease - blood - epidemiology

KW - Female

KW - Humans

KW - Incidence

KW - Lipoprotein(a) - blood

KW - Male

KW - Middle Aged

KW - Risk Assessment - methods

KW - Risk Factors

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

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 -

Impact of lipoprotein(a) level on low-density lipoprotein cholesterol– or apolipoprotein B–related risk of coronary heart disease

Abstract

Keywords

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