Prediction of cardiovascular events with levels of proprotein convertase subtilisin/kexin type 9: A systematic review and meta-analysis

Background and aims: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces atherogenic lipoproteins and could lead to reduction of cardiovascular (CV) events. However, it is unclear whether blood PCSK9 levels predict future CV events. We performed a meta-analysis of all longitudinal studies to determine the ability of PCSK9 levels to predict risk of future CV events. Methods: A comprehensive search of electronic databases was conducted up to February 2016. Longitudinal studies that reported events or relative risk (RR) estimates with 95% confidence intervals (CI) were included. Results: All 9 studies included (12,081 participants, mean follow-up 6.62 years) reported results on total CV events. The pooled RR of total CV events for an increase in baseline PCSK9 by 1 standard deviation (SD) was 1.098 (95% CI, 1.02-1.18), corresponding to a risk increase of 10% (Z = 2.43, p = 0.015). The pooled RR of total CV events for subjects categorized in the highest tertile of baseline PCSK9 was 1.228 (95% CI, 1.035-1.457), corresponding to a risk increase of 23% (Z = 2.35, p = 0.019). When pooled estimates were derived independently for low-and high-CV risk populations, baseline PCSK9 levels predicted total CV events only in apparently healthy subjects (RR = 1.13, 95% CI: 1.050-1.222, Z = 3.21, p = 0.001) and not in populations with established CV or renal disease (RR = 1.09, 95% CI: 0.961-1.23, Z = 1.33, p = 0.182). Conclusions: PCSK9 levels are modestly but significantly associated with increased risk of total CV events. These results suggest a predictive role of PCSK9 levels on CV health and support the possible clinical role of PCSK9 inhibitors. (C) 2016 Elsevier Ireland Ltd. All rights reserved.