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Lipoprotein(a) and residual cardiovascular risk in statin-treated patients

Sam-Lennart Oftadeh1, Andreas Pütz1, Malte Jacobsen1

  • 1Department of Cardiology, Angiology and Intensive Care Medicine (Med. Clinic I), University Hospital RWTH Aachen, RWTH Aachen University, Aachen.

European Journal of Preventive Cardiology
|June 4, 2026
PubMed

Insights

Moderately elevated lipoprotein(a) (Lp[a]) levels increase cardiovascular risk in statin-treated patients. The risk is higher in those without established atherosclerotic cardiovascular disease (ASCVD), suggesting current thresholds may underestimate risk.

Area of Science:

  • Cardiovascular Medicine
  • Lipidology
  • Pharmacology

Background:

  • Elevated lipoprotein(a) (Lp[a]) is a known risk factor for cardiovascular disease (CVD).
  • Current guidelines may not adequately identify individuals at risk due to Lp(a)] levels below established thresholds, particularly in statin-treated populations.
  • Understanding Lp(a)]'s impact across different patient groups, including those with and without established atherosclerotic cardiovascular disease (ASCVD), is crucial for risk stratification.

Purpose of the Study:

  • To assess the cardiovascular risk associated with moderately elevated Lp(a)] levels (<46.8 nmol/L) in statin-treated patients.
  • To explore potential differences in Lp(a)]'s effect on cardiovascular events between patients with and without established ASCVD.
  • To evaluate if current Lp(a)] thresholds underestimate residual cardiovascular risk in high-risk statin-treated individuals.

Main Methods:

  • Analysis of 17,376 UK Biobank participants aged ≥45 years with established ASCVD or type 2 diabetes.
  • Primary endpoint: major adverse cardiovascular events (MACE), including myocardial infarction (MI), stroke, and cardiovascular (CV) mortality.
  • Comparison of CV outcomes between lower (<12.5 nmol/L) and upper (>46.8 nmol/L) Lp(a)] tertiles using adjusted Poisson and generalized additive Cox models, stratified by ASCVD status.

Main Results:

  • The upper Lp(a)] tertile was linked to a 20% higher risk of MACE (p<0.01), 27% higher risk of MI hospitalization (p<0.05), 34% higher rate of coronary revascularization (p<0.001), and 30% increased CV mortality (p<0.05) compared to the lower tertile.
  • Dose-response models revealed a more pronounced effect of Lp(a)] on MACE risk in individuals without established ASCVD.
  • These associations persisted in a statin-treated, high-CV-risk population.

Conclusions:

  • Moderately elevated Lp(a)] levels (>46.8 nmol/L), even below current thresholds, significantly increase CV event risk in high-risk statin-treated patients.
  • The impact of Lp(a)] on MACE is substantially greater in individuals without established ASCVD.
  • Findings suggest current Lp(a)] thresholds may underestimate residual CV risk, particularly in statin-treated patients without prior ASCVD.
Abstract

Keywords:
Cardiovascular Risk FactorsHeart diseaseLipoprotein(a)Statins

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