TY - JOUR
T1 - 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
AU - Hibi, Kiyoshi
AU - Gohbara, Masaomi
AU - Uemura, Kohei
AU - Iwahashi, Noriaki
AU - Okada, Kozo
AU - Iwata, Hiroshi
AU - Fukumoto, Yoshihiro
AU - Hiro, Takafumi
AU - Ozaki, Yukio
AU - Iimuro, Satoshi
AU - Sakuma, Ichiro
AU - Hokimoto, Seiji
AU - Miyauchi, Katsumi
AU - Matsuyama, Yutaka
AU - Nakagawa, Yoshihisa
AU - Ogawa, Hisao
AU - Daida, Hiroyuki
AU - Shimokawa, Hiroaki
AU - Saito, Yasushi
AU - Kimura, Takeshi
AU - Matsuzaki, Masunori
AU - Kimura, Kazuo
AU - Nagai, Ryozo
N1 - Publisher Copyright:
© 2024
PY - 2024/9/1
Y1 - 2024/9/1
N2 - BACKGROUND AND AIMS: 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. METHODS: 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). RESULTS: From 1,478 patients in the 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 ratio [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. CONCLUSIONS: 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.
AB - BACKGROUND AND AIMS: 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. METHODS: 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). RESULTS: From 1,478 patients in the 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 ratio [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. CONCLUSIONS: 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.
KW - Cardiovascular events
KW - Coronary artery disease
KW - Proprotein convertase subtilisin/kexin type 9
KW - Statins
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U2 - 10.1016/j.jacl.2024.07.002
DO - 10.1016/j.jacl.2024.07.002
M3 - Article
C2 - 39278769
AN - SCOPUS:85203790677
SN - 1933-2874
VL - 18
SP - e844-e854
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
IS - 5
ER -