Major cardiovascular events in first-degree relatives of individuals with elevated plasma lipoprotein(a): a registry-based cohort study

Lipoprotein(a) [Lp(a)] levels are genetically determined and causal in the development of atherosclerotic cardiovascular disease. Whether first-degree relatives (FDR) of individuals with elevated Lp(a) levels (≥80th percentile) have an increased cardiovascular disease risk is unknown. Based on 41,304 indexes with a routine plasma Lp(a) measurement, 61,715 FDR without a measured Lp(a) aged 35-69 years (49% women) were identified in the Swedish STRIREG cohort. FDR were stratified according to index 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, ischaemic stroke, coronary revascularization) was investigated. In a nested analysis of 4243 indexes with a first-degree relationship with another index, the concordance of plasma Lp(a) levels was assessed. During a median follow-up of 19 (11-26) years, 2043 FDR had a MACE. The cumulative incidences of MACE in FDR until age of 65 were 6.2%, 7.0%, 7.5%, and 8.1% by increasing index Lp(a) level strata (P<0.001). Compared with FDR in the lowest Lp(a) stratum, there was a higher hazard ratio for MACE by increasing Lp(a) stratum: 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 percentile) and 53% (≥80th percentile). FDR of individuals with elevated Lp(a) levels have a higher incidence of MACE. Cascade screening could be a feasible strategy to identify FDR at heightened risk.