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Measurement assay and inflammation influence the predictive role of levels of proprotein convertase subtilisin/kexin type 9 for cardiovascular events: a meta-analysis and a meta-regression analysis
Authors : D Terentes-Printzios (Athens,GR), C Vlachopoulos (Athens,GR), G Georgiopoulos (Athens,GR), I Skoumas (Athens,GR), I Koutagiar (Athens,GR), N Ioakeimidis (Athens,GR), C Stefanadis (Athens,GR), D Tousoulis (Athens,GR)
1Hippokration Hospital, University of Athens, 1st Department of Cardiology - Athens - Greece
2Hippokration General Hospital - Athens - Greece
Background/Introduction: Blood proprotein convertase subtilisin/kexin type 9 (PCSK9) levels modestly predict future CV events and its inhibition reduces atherogenic lipoproteins and could lead to reduction of cardiovascular (CV) events.
Purpose: We performed a meta-analysis and meta-regression analysis of all longitudinal studies to determine the factors that influence the predictive role of PCSK9.
Methods: A comprehensive search of electronic databases was conducted up to April 2016. Longitudinal studies that reported events or relative risk (RR) estimates with 95% confidence intervals were included. Sensitivity analyses and meta-regression analysis with a random-efffects model were applied.
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). (Figure) 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). When pooled risk estimates were calculated independently for studies that measured PSCK9 with Assay A (i.e. all other ELISA assays apart from the most commonly used) and Assay B (i.e. the most commonly used ELISA assay in the included studies), baseline PCSK9 levels predicted total CV events only when measured with Assay A [(RR=1.15, 95% CI: 1.064–1.234, Z=3.61, P<0.001 versus (RR= 1.073, 95% CI: 0.948–1.214, Z=1.11, P=0.268) for Assay B]. A relevant test for interaction was marginally non-significant (P for interaction=0.073). C-reactive protein (CRP) at enrolment was the only baseline variable that showed a trend to be a predictor of the magnitude of the RR for total CV events (p=0.07) showing an inverse association with the predictive value of high PCSK9 levels.
Conclusions: PCSK9 levels are modestly but significantly associated with increased risk of total CV events and this predictive role is higher in low-inflammatory states and with specific measurement assays.
ESC 365 is supported by Bayer, Boehringer Ingelheim and Lilly Alliance, Bristol-Myers Squibb and Pfizer Alliance, Novartis Pharma AG and Vifor Pharma in the form of educational grants. The sponsors were not involved in the development of this platform and had no influence on its content.
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