PCSK9 as a Biomarker for Cardiovascular Risk

Background: Proprotein convertase subtilisin/kexin 9 (PCSK9) is a protein that prevents low-density lipoprotein (LDL) clearance from plasma through degradation of low-density lipoprotein receptors (LDL-R). Mutations that up- or down-regulate PCSK9 have been shown to affect risk of cardiovascular disease independently of plasma LDL level. In light of these discoveries, plasma PCSK9 level may prove useful as a biomarker for cardiovascular risk. Methods: An exhaustive search of the available medical literature was performed using the MEDLINE (Ovid), CINAHL and Web of Science databases. Keywords included PCSK9, evolocumab, alirocumab, myocardial infarction, cardiovascular disease and coronary artery disease (CAD). Inclusion criteria consisted of studies published in English that were performed on a human population, in the absence of statin therapy with endpoints including occurrence of a first cardiovascular event and severity of coronary artery stenosis. Results: Two studies met eligibility criteria for this systematic review. One was a cross-sectional study and the other was a nested case-control study. The first study was performed on two separate cohorts, with the first cohort of 771 patients showing no correlation between serum PCSK9 level and coronary artery disease (CAD), and the second cohort of 822 patients showing a positive correlation. Both cohorts showed a positive correlation between elevated serum PCSK9 level and acute MI but not prior MI. The second study of 716 women showed no correlation between serum PCSK9 level and risk for future cardiovascular event. Both studies had very low quality of evidence as judged by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guideline. Conclusion: The two studies failed to reach a consensus on whether PCSK9 can be useful as a biomarker for cardiovascular risk; however, transiently elevated serum PCSK9 levels occurred with acute MI. Future studies could be performed to further evaluate the potential use of PCSK9 as a cardiovascular biomarker, as well as a diagnostic marker for myocardial infarction (MI). Keywords: PCSK9, Evolocumab, Alirocumab, Myocardial Infarction, Cardiovascular Disease and Coronary Artery Diseas