Plasma PCSK9 concentrations predict Cardiovascular Events in subjects free of vascular disease and with stable coronary artery disease: Findings from a community-based prospective study and a meta-analysis

Abstract Background The secreted protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular disease. Objective We aimed to determine the relationship between PCSK9 levels and cardiovascular (CV) events using a large cohort and a systematic review with meta-analysis. Methods We analyzed the association of plasma PCSK9 levels with CV events in 1324 subjects (mean age, 61.3 years) from a community-based population in Beijing, China. For the systematic review, we pooled the results of our cohort with other eligible studies in a meta-analysis using a random effects model. Results After a median follow-up interval of 4.8 years, 79 CV events were identified. Cox regression analysis showed that the presence of CV events (HR: 1.83, 95% CI, 1.07-3.17; P=0.046) was related to PCSK9 levels significantly. Combining another 8 prospective cohorts and our findings in a meta-analysis (9 prospective cohorts with a total of 13013 participants were included) showed a positive association between plasma PCSK9 levels and CV events, with a summary HR of 1.26 (95% CI: 1.07-1.50; P=0.007). When pooled estimates were derived for pre-existent and free of coronary artery disease (CAD) populations, baseline PCSK9 levels predicted total CV events only in subjects free of CAD (pooled HR: 1.34, 95% CI, 1.11-1.61; P=0.003). In patients with pre-existent CAD, further subgroup analysis showed that baseline PCSK9 levels predicted CV events only in subjects with stable CAD (pooled HR: 1.58, 95% CI, 1.04-2.38; P=0.030) but not in patients with unstable CAD (pooled HR: 1.02, 95% CI, 0.76-1.35; P=0.908). Conclusion Our findings in the Chinese cohort and the meta-analysis support that high plasma PCSK9 level was a predictive factor for future CV events in subjects free of CAD and with stable CAD but not in patients with established unstable CAD. Keywords PCSK9; cardiovascular events; cohort; meta-analysis.