title: Prediction of cardiovascular events with levels of proprotein convertase subtilisin/kexin type 9: A systematic review and meta-analysis.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors: Hypertension and Cardiometabolic Unit, (1st) Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece. Electronic address: cvlachop@otenet.gr.
authors: Charalambos
authors: C
authors: Vlachopoulos
authors: Hypertension and Cardiometabolic Unit, (1st) Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece.
authors: Dimitrios
authors: D
authors: Terentes-Printzios
authors: Hypertension and Cardiometabolic Unit, (1st) Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece.
authors: Georgios
authors: G
authors: Georgiopoulos
authors: Hypertension and Cardiometabolic Unit, (1st) Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece.
authors: Ioannis
authors: I
authors: Skoumas
authors: Hypertension and Cardiometabolic Unit, (1st) Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece.
authors: Iosif
authors: I
authors: Koutagiar
authors: Hypertension and Cardiometabolic Unit, (1st) Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece.
authors: Nikolaos
authors: N
authors: Ioakeimidis
authors: Hypertension and Cardiometabolic Unit, (1st) Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece.
authors: Christodoulos
authors: C
authors: Stefanadis
authors: Hypertension and Cardiometabolic Unit, (1st) Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece.
authors: Dimitrios
authors: D
authors: Tousoulis
mesh_terms: D000368:Aged; D050197:Atherosclerosis; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D007249:Inflammation; D008074:Lipoproteins / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000097:blood* / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D008074:Lipoproteins; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Cardiovascular risk; Lipids; Meta-analysis; Mortality; PCSK9