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

- PCSK9 levels are associated with increased risk of total CV events.
- This predictive role is attenuated in high CV risk and high inflammatory burden.
- Randomized studies with PCSK9 inhibitors will further elucidate its practical use.

Background and aimsInhibition 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.MethodsA 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.ResultsAll 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).ConclusionsPCSK9 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.