Circulating Mature PCSK9 Level Predicts Diminished Response to Statin Therapy

Background Statin-mediated efficacy of lowering low-density lipoprotein (LDL) cholesterol varies in each individual, and its diminished response is associated with worse outcomes. However, there is no established approach to predict hyporesponse to statins. PCSK9 (proprotein convertase subxilisin/ke...

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Bibliographic Details
Published in:Journal of the American Heart Association 2021-06, Vol.10 (11), p.e019525
Main Authors: Kuyama, Naoto, Kataoka, Yu, Takegami, Misa, Nishimura, Kunihiro, Harada-Shiba, Mariko, Hori, Mika, Ogura, Masatsune, Otsuka, Fumiyuki, Asaumi, Yasuhide, Noguchi, Teruo, Tsujita, Kenichi, Yasuda, Satoshi
Format: Article
Language:English
Subjects:
Aged
Anticholesteremic Agents - therapeutic use
Atherosclerosis - blood
Atherosclerosis - drug therapy
Biomarkers - blood
Coronary Artery Disease - blood
Coronary Artery Disease - drug therapy
Dose-Response Relationship, Drug
Drug Therapy, Combination
Ezetimibe - therapeutic use
Female
Follow-Up Studies
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage
LDL‐C
Male
Middle Aged
Original Research
Proprotein Convertase 9 - blood
proprotein convertase subxilisin/kexin type 9
Prospective Studies
statin
Treatment Outcome
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Summary:Background Statin-mediated efficacy of lowering low-density lipoprotein (LDL) cholesterol varies in each individual, and its diminished response is associated with worse outcomes. However, there is no established approach to predict hyporesponse to statins. PCSK9 (proprotein convertase subxilisin/kexin type 9) is a serine-protease associated with LDL metabolism, which circulates as mature and furin-cleaved PCSK9. Since mature PCSK9 more potently degrades the LDL receptor, its evaluation may enable the identification of statin hyporesponders. Methods and Results We analyzed 101 statin-naive patients with coronary artery disease who commenced a statin. PCSK9 subtypes at baseline and 1 month after statin use were measured by ELISA. Hyporesponse to statins was defined as a percent reduction in LDL cholesterol 228 ng/mL is associated with hyporesponse to statins. This finding suggests that mature PCSK9 might be a potential determinant of hyporesponse to statins.
ISSN:2047-9980
2047-9980
DOI:10.1161/jaha.120.019525