Lipoprotein (a) in primary cardiovascular disease prevention is actionable today

Abstract

Lipoprotein(a) [Lp(a)] has emerged as an important, genetically determined, and independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease. Despite growing evidence of its causal role in cardiovascular morbidity and mortality, its actionability in primary prevention remains underrecognized. This review highlights the contemporary scientific foundation supporting early Lp(a) measurement, elucidates its pathogenic mechanisms, evaluates the evolving therapeutic landscape, and proposes a pragmatic clinical framework for integrating Lp(a) into preventive cardiology today. Through clinical vignettes and current data, we argue that identifying elevated Lp(a) can meaningfully guide risk reclassification, intensify modifiable risk management, and inform patient-centered preventive strategies thereby making Lp(a) testing actionable in contemporary primary prevention.

Fig. 1

Estimated Lifetime Risk of ASCVD by Baseline Risk and Lp(a) Concentration. Lifetime risk of atherosclerotic cardiovascular disease (ASCVD) is shown across five strata of baseline risk (5 %, 10 %, 15 %, 20 %, and 25 %) as determined by the Joint British Societies (JBS3) Lifetime Risk Estimator. The incremental impact of lipoprotein(a) [Lp(a)] is modeled across plasma concentration categories (<30, 30–50, 51–75, 76–100, and 101–150 mg/dL), assuming a constant hazard ratio for Lp(a) across all baseline risk levels. Risk estimates are derived from a cohort of 415,274 UK Biobank participants of European ancestry. Modified from data presented in Fig. 6 and Supplementary Table 3, as published in the 2022 European Atherosclerosis Society Consensus Statement [12].

Fig. 2A

Familial Hypercholesterolemia with Elevated Lp(a).

Fig. 2B

Family History of Aortic Stenosis with High Lp(a).

Fig. 2C

Family History of Premature Coronary Heart Disease.

Fig. 2D

Borderline LDL-C and Elevated Lp(a) in a ‘Low-Risk’ Patient.

Fig. 2E

Isolated High Lp(a) Discovered by Screening.