Should a new parameter be included in the lipid profile for primary prevention? In any case, this is what the study published in JAMA Cardiology on January 7, 2026 suggests. It indeed analyzes the association between concentrations of lipoprotein(a) [Lp(a)] and very long-term cardiovascular risk in initially healthy women. The main objective was to evaluate the cumulative risk over 30 years of cardiovascular events according to different clinical thresholds of Lp(a), in a context of primary prevention, in order to shed light on the relevance of more systematic screening and consideration of this biomarker.
A median duration of 30 years
The study is based on data from the Women’s Health Study, a large prospective American cohort including 27,748 women aged at least 45 years, with no history of cardiovascular disease, cancer or major pathology at the time of inclusion. The participants were followed for a median duration of almost 30 years. Plasma Lp(a) concentrations were measured at baseline, then analyzed according to usual clinical thresholds (including ≥30 mg/dL, ≥50 mg/dL and ≥120 mg/dL), as well as according to population distribution percentiles. A genetic analysis was also carried out, focusing on the rs3798220 polymorphism of the LPA gene, known to be associated with high levels of Lp(a).
Outcomes included major cardiovascular events (including myocardial infarction, stroke and cardiovascular death), coronary heart disease, ischemic stroke in isolation and cardiovascular mortality. Analyzes were adjusted for major traditional cardiovascular risk factors, including age, smoking, high blood pressure, diabetes, body mass index and LDL cholesterol.
Association between high Lp(a) level and CV risk
The results show a clear association between high Lp(a) levels and long-term cardiovascular risk. Women with Lp(a) greater than 30 mg/dL or above the 75th percentile had a significantly increased risk of major cardiovascular events and coronary heart disease over 30 years compared to those with lower concentrations. This excess risk was particularly marked for coronary heart disease. On the other hand, the associations with ischemic stroke and cardiovascular mortality became especially significant for very high concentrations of Lp(a), particularly from 120 mg/dL or beyond the 99th percentile.
Analyzes in terms of relative risk show hazard ratios of the order of 1.5 to 2 depending on the type of event and the threshold considered, after multivariate adjustment. These results confirm that Lp(a) constitutes an independent risk factor, not redundant with other classic lipid parameters. Genetic analysis reinforces this observation, with carriers of the rs3798220 allele exhibiting both higher concentrations of Lp(a) and an increased risk of major cardiovascular events, suggesting a likely causal link.
The authors underline the clinical interest of these data in a context where Lp(a) remains insufficiently dosed in daily practice, particularly among women in primary prevention. The study shows that the risk associated with Lp(a) is fully expressed over the very long term, which may explain why its impact is sometimes underestimated in shorter follow-up studies. These results argue in favor of dosing at least once in a lifetime, in particular to identify patients with very high values, likely to benefit from more intensive management of other risk factors and, in the future, from specific treatments for Lp(a).
