Serum mature and furin-cleaved proprotein convertase subtilisin/kexin type 9 levels and their association with cardiovascular events in statin-treated patients with cardiovascular disease

• Published in: Journal of clinical lipidology
• Main Authors: Hibi, Kiyoshi, Gohbara, Masaomi, Uemura, Kohei, Iwahashi, Noriaki, Okada, Kozo, Iwata, Hiroshi, Fukumoto, Yoshihiro, Hiro, Takafumi, Ozaki, Yukio, Iimuro, Satoshi, Sakuma, Ichiro, Hokimoto, Seiji, Miyauchi, Katsumi, Matsuyama, Yutaka, Nakagawa, Yoshihisa, Ogawa, Hisao, Daida, Hiroyuki, Shimokawa, Hiroaki, Saito, Yasushi, Kimura, Takeshi, Matsuzaki, Masunori, Kimura, Kazuo, Nagai, Ryozo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.07.2024
• Subjects: Cardiovascular events; Coronary artery disease; Proprotein convertase subtilisin/kexin type 9; Statins; Cardiovascular events; Proprotein convertase subtilisin/kexin type 9; Coronary artery disease; Statins
• ISSN: 1933-2874
• DOI: 10.1016/j.jacl.2024.07.002

•Previous studies have not found a consistent association between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and cardiovascular events partly due to measurement methods that cannot distinguish between mature (uncleaved) and furin-cleaved forms of PCSK9.•Risk of the cardiovascular events in patients with the highest quartile of mature PCSK9 levels was similar to that in the lowest quartile.•PCSK9 levels could not predict future cardiovascular events, even when mature PCSK9 levels were measured in statin-treated patients with stable coronary artery disease. Previous studies have not found a consistent association between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the risk of cardiovascular events partly due to measurement methods that cannot distinguish between uncleaved and furin-cleaved forms of PCSK9. This is a prespecified sub-study of the REAL-CAD study which is a prospective, multicenter, randomized trial to compare high- versus low-dose statin in patients with stable coronary artery disease (CAD). The primary endpoint was major adverse cerebrovascular and cardiovascular events (MACCE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. In this case-cohort study, serum mature (uncleaved) and furin-cleaved PCSK9 levels obtained at 6 months after randomization were measured among 426 participants who developed MACCE (cases) and 1,478 randomly selected participants (sub-cohort). From 1,478 patients in sub-cohort, the Cox proportional hazards models with a pseudolikelihood method for case-cohort design revealed that the risk of the primary endpoint in patients with the highest quartile of mature PCSK9 levels was similar to that in the lowest quartile (hazard ration [HR] 0.809; 95% confidence intervals [CI], 0.541-1.209). Similarly, the HR for the highest to lowest quartiles of furin-cleaved PCSK9 was 0.948 [95% CI, 0.645-1.392] (P = 0.784). Compared to the lowest quartile, neither serum mature nor furin-cleaved PCSK9 levels predicted MACCE. In a large-scale secondary prevention cohort, serum mature and furin-cleaved PCSK9 levels did not provide useful information for predicting future cardiovascular events in statin-treated patients with stable CAD.