Lipoprotein (a) and Incident Coronary Heart Disease in the Community: Impact of Traditional Cardiovascular Risk Factors

BiomarCaRE investigators; Natalie Arnold; Alina Goßling; Benjamin Bay; Jessica Weimann; Christopher Blaum; Fabian J Brunner; Marco M Ferrario; Paolo Brambilla; Giancarlo Cesana; Valerio Leoni; Luigi Palmieri; Chiara Donfrancesco; Teresa Padró; Jonas Andersson; Pekka Jousilahti; Francisco Ojeda; Tanja Zeller; Allan Linneberg; Stefan Söderberg; Licia Iacoviello; Francesco Gianfagna; 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:10.1093/eurjpc/zwaf340

Lipoprotein (a) and Incident Coronary Heart Disease in the Community: Impact of Traditional Cardiovascular Risk Factors

BiomarCaRE investigators
, Natalie Arnold
, Alina Goßling
, Benjamin Bay
, Jessica Weimann
, Christopher Blaum
, Fabian J Brunner
, Marco M Ferrario
, Paolo Brambilla
, Giancarlo Cesana
, Valerio Leoni
, Luigi Palmieri
, Chiara Donfrancesco
, Teresa Padró
, Jonas Andersson
, Pekka Jousilahti
, Francisco Ojeda
, Tanja Zeller
, Allan Linneberg
, Stefan Söderberg

Licia Iacoviello, Francesco Gianfagna, 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 (Lead / Corresponding author)

Cardiovascular Research

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

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Abstract

AIMS

Deleterious effects Lipoprotein (a) (Lp(a)) might be mitigated by overall cardiovascular (CV) risk reduction. However, data on the relationship between increased Lp(a) and incident coronary heart disease (CHD) according to the distribution of modifiable CV risk factors (CVRF) at baseline are still scarce. We investigated the association between high Lp(a) and incident CHD in the general population, depending on the presence/absence of four major CVRFs (hypertension, diabetes, hypercholesterolemia, smoking) at baseline.

METHODS

Overall 66,495 CHD-free individuals from eight European prospective population-based cohorts were included. The cohort was stratified according to CVRF burden at baseline in "0/1 CVRF" (low risk; n= 41,770) and"≥2 CVRFs" (increased risk; n=24,725). Fine and Gray competing risk-adjusted models were calculated for the association between Lp(a) mass (<90th versus ≥90th percentile (pctl.); cut-off 43.2 mg/dL) and future CHD events.

RESULTS: During a median follow-up of 9.7 years, 3,467 incident CHD events occurred. Despite being at very low absolute risk based on traditional CVRF, individuals with 0/1CVRF demonstrated a strong association between increased Lp(a) mass (≥90th pctl.) and future CHD events, which was comparable to the association observed among individuals with ≥2 CVRFs. The fully-adjusted sub-distribution Hazard Ratios [sHRs] for elevated Lp(a) were 1.38 (95% CI, 1.12-1.71) versus 1.27 (95% CI, 1.10-1.46) in those having 0/1 versus ≥2 CVRFs at baseline (Pinteraction0.50).

CONCLUSION

Among CHD-free subjects, high Lp(a) was related to adverse outcome even in individuals with no or only one CVRF at baseline, thereby generating substantial challenges in mitigating Lp(a)-associated CHD risk in very low risk populations.

Original language	English
Article number	zwaf340
Number of pages	9
Journal	European Journal of Preventive Cardiology
Early online date	12 Jun 2025
DOIs	https://doi.org/10.1093/eurjpc/zwaf340
Publication status	E-pub ahead of print - 12 Jun 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Lipoprotein (a)
Traditional modifiable risk factors
Incident coronary heart disease
Primary prevention
General Population

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10.1093/eurjpc/zwaf340Licence: CC BY-NC

Final Published VersionFinal published version, 487 KBLicence: CC BY-NC

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BiomarCaRE investigators, Arnold, N., Goßling, A., Bay, B., Weimann, J., Blaum, C., Brunner, F. J., Ferrario, M. M., Brambilla, P., Cesana, G., Leoni, V., Palmieri, L., Donfrancesco, C., Padró, T., Andersson, J., Jousilahti, P., Ojeda, F., Zeller, T., Linneberg, A., ... Koenig, W. (2025). Lipoprotein (a) and Incident Coronary Heart Disease in the Community: Impact of Traditional Cardiovascular Risk Factors. European Journal of Preventive Cardiology, Article zwaf340. Advance online publication. https://doi.org/10.1093/eurjpc/zwaf340

@article{58823d271eec43c39fb246a56c64d9b8,

title = "Lipoprotein (a) and Incident Coronary Heart Disease in the Community: Impact of Traditional Cardiovascular Risk Factors",

abstract = "AIMS Deleterious effects Lipoprotein (a) (Lp(a)) might be mitigated by overall cardiovascular (CV) risk reduction. However, data on the relationship between increased Lp(a) and incident coronary heart disease (CHD) according to the distribution of modifiable CV risk factors (CVRF) at baseline are still scarce. We investigated the association between high Lp(a) and incident CHD in the general population, depending on the presence/absence of four major CVRFs (hypertension, diabetes, hypercholesterolemia, smoking) at baseline.METHODS Overall 66,495 CHD-free individuals from eight European prospective population-based cohorts were included. The cohort was stratified according to CVRF burden at baseline in {"}0/1 CVRF{"} (low risk; n= 41,770) and{"}≥2 CVRFs{"} (increased risk; n=24,725). Fine and Gray competing risk-adjusted models were calculated for the association between Lp(a) mass (<90th versus ≥90th percentile (pctl.); cut-off 43.2 mg/dL) and future CHD events.RESULTS: During a median follow-up of 9.7 years, 3,467 incident CHD events occurred. Despite being at very low absolute risk based on traditional CVRF, individuals with 0/1CVRF demonstrated a strong association between increased Lp(a) mass (≥90th pctl.) and future CHD events, which was comparable to the association observed among individuals with ≥2 CVRFs. The fully-adjusted sub-distribution Hazard Ratios [sHRs] for elevated Lp(a) were 1.38 (95\% CI, 1.12-1.71) versus 1.27 (95\% CI, 1.10-1.46) in those having 0/1 versus ≥2 CVRFs at baseline (Pinteraction0.50).CONCLUSION Among CHD-free subjects, high Lp(a) was related to adverse outcome even in individuals with no or only one CVRF at baseline, thereby generating substantial challenges in mitigating Lp(a)-associated CHD risk in very low risk populations.",

keywords = "Lipoprotein (a), Traditional modifiable risk factors, Incident coronary heart disease, Primary prevention, General Population",

author = "\{BiomarCaRE investigators\} and Natalie Arnold and Alina Go{\ss}ling and Benjamin Bay and Jessica Weimann and Christopher Blaum and Brunner, \{Fabian J\} and Ferrario, \{Marco M\} and Paolo Brambilla and Giancarlo Cesana and Valerio Leoni and Luigi Palmieri and Chiara Donfrancesco and Teresa Padr{\'o} and Jonas Andersson and Pekka Jousilahti and Francisco Ojeda and Tanja Zeller and Allan Linneberg and Stefan S{\"o}derberg and Licia Iacoviello and Francesco Gianfagna 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",

note = "{\textcopyright} The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2025",

month = jun,

day = "12",

doi = "10.1093/eurjpc/zwaf340",

language = "English",

journal = "European Journal of Preventive Cardiology",

issn = "2047-4873",

publisher = "Oxford University Press",

}

BiomarCaRE investigators, Arnold, N, Goßling, A, Bay, B, Weimann, J, Blaum, C, Brunner, FJ, Ferrario, MM, Brambilla, P, Cesana, G, Leoni, V, Palmieri, L, Donfrancesco, C, Padró, T, Andersson, J, Jousilahti, P, Ojeda, F, Zeller, T, Linneberg, A, Söderberg, S, Iacoviello, L, Gianfagna, F, 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 2025, 'Lipoprotein (a) and Incident Coronary Heart Disease in the Community: Impact of Traditional Cardiovascular Risk Factors', European Journal of Preventive Cardiology. https://doi.org/10.1093/eurjpc/zwaf340

TY - JOUR

T1 - Lipoprotein (a) and Incident Coronary Heart Disease in the Community

T2 - Impact of Traditional Cardiovascular Risk Factors

AU - BiomarCaRE investigators

AU - Arnold, Natalie

AU - Goßling, Alina

AU - Bay, Benjamin

AU - Weimann, Jessica

AU - Blaum, Christopher

AU - Brunner, Fabian J

AU - Ferrario, Marco M

AU - Brambilla, Paolo

AU - Cesana, Giancarlo

AU - Leoni, Valerio

AU - Palmieri, Luigi

AU - Donfrancesco, Chiara

AU - Padró, Teresa

AU - Andersson, Jonas

AU - Jousilahti, Pekka

AU - Ojeda, Francisco

AU - Zeller, Tanja

AU - Linneberg, Allan

AU - Söderberg, Stefan

AU - Iacoviello, Licia

AU - Gianfagna, Francesco

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 - 2025/6/12

Y1 - 2025/6/12

N2 - AIMS Deleterious effects Lipoprotein (a) (Lp(a)) might be mitigated by overall cardiovascular (CV) risk reduction. However, data on the relationship between increased Lp(a) and incident coronary heart disease (CHD) according to the distribution of modifiable CV risk factors (CVRF) at baseline are still scarce. We investigated the association between high Lp(a) and incident CHD in the general population, depending on the presence/absence of four major CVRFs (hypertension, diabetes, hypercholesterolemia, smoking) at baseline.METHODS Overall 66,495 CHD-free individuals from eight European prospective population-based cohorts were included. The cohort was stratified according to CVRF burden at baseline in "0/1 CVRF" (low risk; n= 41,770) and"≥2 CVRFs" (increased risk; n=24,725). Fine and Gray competing risk-adjusted models were calculated for the association between Lp(a) mass (<90th versus ≥90th percentile (pctl.); cut-off 43.2 mg/dL) and future CHD events.RESULTS: During a median follow-up of 9.7 years, 3,467 incident CHD events occurred. Despite being at very low absolute risk based on traditional CVRF, individuals with 0/1CVRF demonstrated a strong association between increased Lp(a) mass (≥90th pctl.) and future CHD events, which was comparable to the association observed among individuals with ≥2 CVRFs. The fully-adjusted sub-distribution Hazard Ratios [sHRs] for elevated Lp(a) were 1.38 (95% CI, 1.12-1.71) versus 1.27 (95% CI, 1.10-1.46) in those having 0/1 versus ≥2 CVRFs at baseline (Pinteraction0.50).CONCLUSION Among CHD-free subjects, high Lp(a) was related to adverse outcome even in individuals with no or only one CVRF at baseline, thereby generating substantial challenges in mitigating Lp(a)-associated CHD risk in very low risk populations.

AB - AIMS Deleterious effects Lipoprotein (a) (Lp(a)) might be mitigated by overall cardiovascular (CV) risk reduction. However, data on the relationship between increased Lp(a) and incident coronary heart disease (CHD) according to the distribution of modifiable CV risk factors (CVRF) at baseline are still scarce. We investigated the association between high Lp(a) and incident CHD in the general population, depending on the presence/absence of four major CVRFs (hypertension, diabetes, hypercholesterolemia, smoking) at baseline.METHODS Overall 66,495 CHD-free individuals from eight European prospective population-based cohorts were included. The cohort was stratified according to CVRF burden at baseline in "0/1 CVRF" (low risk; n= 41,770) and"≥2 CVRFs" (increased risk; n=24,725). Fine and Gray competing risk-adjusted models were calculated for the association between Lp(a) mass (<90th versus ≥90th percentile (pctl.); cut-off 43.2 mg/dL) and future CHD events.RESULTS: During a median follow-up of 9.7 years, 3,467 incident CHD events occurred. Despite being at very low absolute risk based on traditional CVRF, individuals with 0/1CVRF demonstrated a strong association between increased Lp(a) mass (≥90th pctl.) and future CHD events, which was comparable to the association observed among individuals with ≥2 CVRFs. The fully-adjusted sub-distribution Hazard Ratios [sHRs] for elevated Lp(a) were 1.38 (95% CI, 1.12-1.71) versus 1.27 (95% CI, 1.10-1.46) in those having 0/1 versus ≥2 CVRFs at baseline (Pinteraction0.50).CONCLUSION Among CHD-free subjects, high Lp(a) was related to adverse outcome even in individuals with no or only one CVRF at baseline, thereby generating substantial challenges in mitigating Lp(a)-associated CHD risk in very low risk populations.

KW - Lipoprotein (a)

KW - Traditional modifiable risk factors

KW - Incident coronary heart disease

KW - Primary prevention

KW - General Population

U2 - 10.1093/eurjpc/zwaf340

DO - 10.1093/eurjpc/zwaf340

M3 - Article

C2 - 40504886

SN - 2047-4873

JO - European Journal of Preventive Cardiology

JF - European Journal of Preventive Cardiology

M1 - zwaf340

ER -

Lipoprotein (a) and Incident Coronary Heart Disease in the Community: Impact of Traditional Cardiovascular Risk Factors

Abstract

UN SDGs

Keywords

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