Circulating lipoprotein (a) and all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis

Aims: To investigate the association between circulating lipoprotein(a) (Lp(a)) and risk of all-cause and cause-specific mortality in the general population and in patients with chronic diseases, and to elucidate the dose-response relations. Methods and results: We searched literature to find prospective studies reporting adjusted risk estimates on the association of Lp(a) and mortality outcomes. Forty-three publications, reporting on 75 studies (957,253 participants), were included. The hazard ratios (HRs) and 95% confidence intervals (95%CI) for the top versus bottom tertile of Lp(a) levels and risk of all-cause mortality were 1.09 (95%CI: 1.01–1.18, I²: 75.34%, n = 19) in the general population and 1.18 (95%CI: 1.04–1.34, I²: 52.5%, n = 12) in patients with cardiovascular diseases (CVD). The HRs for CVD mortality were 1.33 (95%CI: 1.11–1.58, I²: 82.8%, n = 31) in the general population, 1.25 (95%CI: 1.10–1.43, I²: 54.3%, n = 17) in patients with CVD and 2.53 (95%CI: 1.13–5.64, I²: 66%, n = 4) in patients with diabetes mellitus. Linear dose-response analyses revealed that each 50 mg/dL increase in Lp(a) levels was associated with 31% and 15% greater risk of CVD death in the general population and in patients with CVD. No non-linear dose-response association was observed between Lp(a) levels and risk of all-cause or CVD mortality in the general population or in patients with CVD (P_nonlinearity > 0.05). Conclusion: This study provides further evidence that higher Lp(a) levels are associated with higher risk of all-cause mortality and CVD-death in the general population and in patients with CVD. These findings support the ESC/EAS Guidelines that recommend Lp(a) should be measured at least once in each adult person’s lifetime, since our study suggests those with higher Lp(a) might also have higher risk of mortality.