Lipoprotein(a) and risk of sudden cardiac death in middle-aged Finnish men: A new prospective cohort study

Background

Lipoprotein(a) [Lp(a)] is an established and independent risk factor for cardiovascular outcomes. However, the relationship of Lp(a) with risk of sudden cardiac death (SCD) is unknown. We aimed to assess the association of Lp(a) with risk of SCD in the Kuopio Ischemic Heart Disease prospective cohort study of 1,881 men aged 42-61 years at recruitment.

Methods and Results

Plasma Lp(a) concentration was assessed at baseline and repeat measurements made several years apart. After a median follow-up of 24.7 years, 141 SCDs were recorded. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed and were corrected for within-person variability in Lp(a) levels. The regression dilution ratio of loge Lp(a) adjusted for age was 0.84 (95% CI: 0.81-0.88). Lipoprotein(a) levels were log-linearly associated with risk of SCD. In analyses adjusted for established risk factors, the HR (95% CI) for SCD per 1 standard deviation (3.56-fold) higher baseline loge Lp(a) was 1.24 (1.05-1.47; P = 0.013). This remained consistent on further adjustment for alcohol consumption, resting heart rate, lipids, and C-reactive protein 1.23 (1.04-1.46; P = 0.018). HRs remained unchanged after accounting for incident coronary events and did not vary importantly in several relevant clinical subgroups. Adding Lp(a) to a SCD risk prediction model did not significantly improve risk discrimination beyond established risk factors, but improved the continuous net reclassification 30.2% (1.1 to 59.2%, P = 0.042).

Conclusions

Available evidence shows a continuous and independent association between Lp(a) levels and risk of SCD. Further research is needed to replicate these findings.