Key result
Top-percentile Lp(a) in index patients is linked to ~28% higher MACE risk in first-degree relatives.
Why the study?
Does having a first-degree relative with elevated Lp(a) increase the risk of major adverse cardiovascular events?
Cohort (n=61,715)
Does having a first-degree relative with elevated Lp(a) increase the risk of major adverse cardiovascular events?
Hazard Ratio: 1.28 (95% CI 1.06–1.55)
Absolute Event Rate: 8.1% vs 6.2%
p-value: p=<0.001
First-degree relatives of individuals with elevated Lp(a) (≥80th percentile) have a significantly higher incidence of cardiovascular events, supporting the use of family cascade screening.
Background and Aims Elevated lipoprotein(a) [Lp(a)] is a hereditary dyslipoproteinemia causing atherosclerosis. The aim was to study the development of incident atherosclerotic cardiovascular disease in first-degree relatives (FDRs) to individuals with a measured Lp(a). Methods Based on 41,304 indexes with a clinical routine plasma Lp(a) measurement, 61,715 FDRs without a measured Lp(a) aged 35 to 69 years (49% women) were identified in the Swedish STRIREG cohort. FDRs were stratified according to their indexes’ Lp(a) percentile level; <50th, 50–<80th, 80–<95th and ≥95th. In competing risk-adjusted cumulative incidence and adjusted Cox proportional hazards regressions, the association between Lp(a) strata and major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, ischemic stroke, coronary revascularization) was investigated. In a nested analysis of 4,243 indexes with a first-degree relationship with another index, the plasma Lp(a) concordance was assessed. Results During a median follow-up time of 19 (11–26) years, 2,043 FDRs had a MACE. At age 65 years, the cumulative incidences for MACE in FDRs were 6.2%, 7.0%, 7.5% and 8.1% by increasing index Lp(a) stratum (P<0.001). Compared to FDRs in the lowest Lp(a) stratum, there was a stepwise higher hazard ratio for MACE by increasing Lp(a) strata; 1.08 (95% confidence interval, 0.97–1.19), 1.30 (1.15–1.47), and 1.28 (1.06–1.55, Ptrend<0.001). The Lp(a) concordance was 86% (<80th) and 53% (≥80th). Conclusion FDRs to individuals with Lp(a)≥80th percentile have a higher incidence of cardiovascular events. Family cascade screening measuring plasma Lp(a) may be an effective method to identify FDRs at heightened cardiovascular risk.
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Kindborg et al. (2025) conducted a cohort in First-degree relatives of individuals with measured Lp(a) (n=61,715). Elevated index Lp(a) percentile level (≥95th percentile) vs. Index Lp(a) <50th percentile was evaluated on Major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, ischemic stroke, coronary revascularization) (HR 1.28, 95% CI 1.06-1.55, p=<0.001). First-degree relatives of individuals with Lp(a) ≥95th percentile had a higher risk of MACE compared to those with index Lp(a) <50th percentile (HR 1.28; 95% CI 1.06-1.55; Ptrend<0.001).
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