Abstract
Background: A large amount of evidence suggests that proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors have clinical benefits in patients with cardiovascular disease (CVD). However, whether PCSK9 concentrations predict future cardiovascular (CV) events remains unclear.Methods: We conducted a meta-analysis to investigate the ability of PCSK9 concentrations to predict future CV events in patients with established CVD. A comprehensive search of electronic databases was conducted in June 2021. We included relative risk (RR) estimates with 95% CI or events of interest.Results: Eleven cohort studies including 8,471 patients with CVD were enrolled. The pooled RR of CV events for the increase in the circulating baseline PCSK9 concentrations by 1 SD showed a positive association in a random-effect model (RR 1.226, 95% CI: 1.055–1.423, P = 0.008). Similarly, the risk of the total CV events increased by 52% in the patients in the highest tertile compared with those in the lowest tertile of circulating PCSK9 concentrations (RR 1.523, 95% CI: 1.098–2.112, P = 0.012). The association between PCSK9 and CV events was stronger in stable patients with CVD, patients treated with statins, and Asian patients.Conclusions: High PCSK9 concentrations are significantly related to the increased risk of future CV events. These results enrich the knowledge of PCSK9 function and suggest the further possible clinical role of PCSK9 inhibitors.
Highlights
Cardiovascular disease remains one of the most common causes of morbidity and mortality worldwide
None of the patients included in this meta-analysis were treated with drugs targeting proprotein convertase subtilisin/Kexin type 9 (PCSK9)
The PCSK9 concentrations significantly predicted the CV events in the statin use group but not in the nonstatin group (RR 1.250, 95% CI: 1.033–1.513, P = 0.022; relative risks (RRs) 1.186, 95% CI: 0.885–1.589, P = 0.252 respectively) (Figure 5A)
Summary
Cardiovascular disease remains one of the most common causes of morbidity and mortality worldwide. A vital challenge for clinicians managing patients with cardiovascular disease (CVD) is to reduce the risk of recurrent events. Identifying specific patients with CVD who have an enhanced risk for future cardiovascular (CV) events is important. Gain of function proprotein convertase subtilisin/Kexin type 9 (PCSK9) mutations are the third most common genetic cause of autosomal dominant family hypercholesterolemia, and these mutations upregulate LDL-C concentrations and increase the risk of CVD [3]. PCSK9 inhibitors are established as novel targets that lower lipids and result in clinical improvement [5, 6], the value of PCSK9 concentrations as a predictor for CV events is unclear. A large amount of evidence suggests that proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors have clinical benefits in patients with cardiovascular disease (CVD). Whether PCSK9 concentrations predict future cardiovascular (CV) events remains unclear
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