Abstract 16548: The Association of Mature Proprotein Convertase Subtilisin/Kexin Type 9 With Atherosclerotic Coronary Artery Disease in Patients With Familial Hypercholesteremia
Background: Familial hypercholesterolemia (FH) increases a risk of premature atherosclerotic coronary artery disease (CAD). Proprotein convertase subtilisin/kexin type 9 (PCSK9), an important contributor to LDL metabolism in FH, has been shown to promote atherosclerosis. While PCSK9 circulates as two subtypes: mature and furin-cleaved forms, their atherogenic effects remain to be elucidated. We analyzed the relationship of PCSK9 subtypes with atherosclerotic CAD in FH cases.
Method: Serum mature and furin-cleaved PCSK9 levels were measured in 137 FH subjects receiving a statin by commercially available ELISA (BML.Inc, Tokyo, Japan). CAD was defined as the presence of significant coronary artery stenosis requiring revascularization. The association of mature and furin-cleaved PCSK9 with prevalence of CAD were analyzed, respectively.
Results: Under lipid lowering therapies (high-intensity statin=52%, ezetimibe=22%), LDL-C, median mature and furin-cleaved PCSK9 levels were 128±36 mg/dl, 287 and 53 ng/ml, respectively. Mature PCSK9 was correlated with triglycerides (r=0.20, p=0.02). Furthermore, an elevated mature PCSK9 level was significantly associated with a higher prevalence of CAD [odds ratio (OR) for an increase per standard deviation=1.47, 95%CI 1.02-2.13, p=0.03]. By contrast, there were no significant relationships between furin-cleaved PCSK9 and prevalence of CAD. The association of mature PCSK9 with CAD was further analyzed by using its tertile (Figure). On multivariate analysis, mature PCSK9 level >383 ng/ml (=upper tertile) was an independent predictor for the presence of CAD [lower v. upper tertile: OR=3.92, 95%CI 1.33-11.6, p=0.01, lower v. mid tertile: OR=1.18, 95%CI 0.38-3.65, p=0.78].
Conclusion: Higher prevalence of atherosclerotic CAD was observed in association with mature PCSK9 level. Our findings indicate mature PCSK9 as a potential risk marker to identify high-risk FH subjects harboring atherosclerotic CAD.
Author Disclosures: K. Nakao: None. Y. Kataoka: None. T. Noguchi: None. H. Hattori: None. M. Ogura: None. S. Yasuda: None. M. Harada-Shiba: None.
- © 2016 by American Heart Association, Inc.