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Xiaona Wang
Chinese PLA General Hospital
Corresponding Author
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Background The secreted protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular disease. Objective We aimed to determine the relationship between PCSK9 levels and cardiovascular (CV) events using a large cohort and a systematic review with meta-analysis.
Methods We analyzed the association of plasma PCSK9 levels with CV events in 1324 subjects (mean age, 61.3 years) from a community-based population in Beijing, China. For the systematic review, we pooled the results of our cohort with other eligible studies in a meta-analysis using a random effects model.
Results After a median follow-up interval of 4.8 years, 79 CV events were identified. Cox regression analysis showed that the presence of CV events (HR: 1.83, 95% CI, 1.07-3.17; P=0.046) was related to PCSK9 levels significantly. Combining another 8 prospective cohorts and our findings in a meta-analysis (9 prospective cohorts with a total of 13013 participants were included) showed a positive association between plasma PCSK9 levels and CV events, with a summary HR of 1.26 (95% CI: 1.07-1.50; P=0.007). When pooled estimates were derived for pre-existent and free of coronary artery disease (CAD) populations, baseline PCSK9 levels predicted total CV events only in subjects free of CAD (pooled HR: 1.34, 95% CI, 1.11-1.61; P=0.003). In patients with pre-existent CAD, further subgroup analysis showed that baseline PCSK9 levels predicted CV events only in subjects with stable CAD (pooled HR: 1.58, 95% CI, 1.04-2.38; P=0.030) but not in patients with unstable CAD (pooled HR: 1.02, 95% CI, 0.76-1.35; P=0.908).
Conclusion Our findings in the Chinese cohort and the meta-analysis support that high plasma PCSK9 level was a predictive factor for future CV events in subjects free of CAD and with stable CAD but not in patients with established unstable CAD. Keywords PCSK9; cardiovascular events; cohort; meta-analysis.
Keywords
PCSK9, cardiovascular events, cohort, meta-analysis
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Xiaona Wang
Chinese PLA General Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 10 May, 2020
No community comments so far
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Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Endocrinology & Metabolism
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background The secreted protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular disease. Objective We aimed to determine the relationship between PCSK9 levels and cardiovascular (CV) events using a large cohort and a systematic review with meta-analysis.
Methods We analyzed the association of plasma PCSK9 levels with CV events in 1324 subjects (mean age, 61.3 years) from a community-based population in Beijing, China. For the systematic review, we pooled the results of our cohort with other eligible studies in a meta-analysis using a random effects model.
Results After a median follow-up interval of 4.8 years, 79 CV events were identified. Cox regression analysis showed that the presence of CV events (HR: 1.83, 95% CI, 1.07-3.17; P=0.046) was related to PCSK9 levels significantly. Combining another 8 prospective cohorts and our findings in a meta-analysis (9 prospective cohorts with a total of 13013 participants were included) showed a positive association between plasma PCSK9 levels and CV events, with a summary HR of 1.26 (95% CI: 1.07-1.50; P=0.007). When pooled estimates were derived for pre-existent and free of coronary artery disease (CAD) populations, baseline PCSK9 levels predicted total CV events only in subjects free of CAD (pooled HR: 1.34, 95% CI, 1.11-1.61; P=0.003). In patients with pre-existent CAD, further subgroup analysis showed that baseline PCSK9 levels predicted CV events only in subjects with stable CAD (pooled HR: 1.58, 95% CI, 1.04-2.38; P=0.030) but not in patients with unstable CAD (pooled HR: 1.02, 95% CI, 0.76-1.35; P=0.908).
Conclusion Our findings in the Chinese cohort and the meta-analysis support that high plasma PCSK9 level was a predictive factor for future CV events in subjects free of CAD and with stable CAD but not in patients with established unstable CAD. Keywords PCSK9; cardiovascular events; cohort; meta-analysis.
Figure 1
Figure 2
Figure 3
Figure 4
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