Abstract 20898: PCSK9 Levels and Cardiovascular Outcomes: A Systematic Review, Meta-Analysis and Meta-Regression Analysis
Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein that promotes degradation of the low-density lipoprotein receptor. Inhibition of 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.
Hypothesis: We performed a meta-analysis of all longitudinal studies to determine the ability of PCSK9 levels to predict risk of future CV events and dissected factors influencing this predictive ability.
Methods: We searched the MEDLINE, Cochrane and EMBASE databases, and reviewed reference lists from retrieved articles and abstracts from large international CV conventions until February 2016. Longitudinal studies that reported events or relative risk (RR) estimates with 95% confidence intervals were included. Two reviewers extracted data independently and summary estimates of association were obtained using a random-effects model.
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 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.
Author Disclosures: D. Terentes-Printzios: None. C. Vlachopoulos: None. G. Georgiopoulos: None. I. Skoumas: None. I. Koutagiar: None. N. Ioakeimidis: None. C. Stefanadis: None. D. Tousoulis: None.
- © 2016 by American Heart Association, Inc.