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...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2021-06-01
|
Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
Subjects: | |
Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.120.019525 |
id |
doaj-74fedaa5ab9f4a999ab411678695895e |
---|---|
record_format |
Article |
spelling |
doaj-74fedaa5ab9f4a999ab411678695895e2021-09-14T15:27:52ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-06-01101110.1161/JAHA.120.019525Circulating Mature PCSK9 Level Predicts Diminished Response to Statin TherapyNaoto Kuyama0Yu Kataoka1Misa Takegami2Kunihiro Nishimura3Mariko Harada‐Shiba4Mika Hori5Masatsune Ogura6Fumiyuki Otsuka7Yasuhide Asaumi8Teruo Noguchi9Kenichi Tsujita10Satoshi Yasuda11Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka JapanDepartment of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka JapanDepartment of Preventive Medicine and Epidemiology National Cerebral and Cardiovascular Center Osaka JapanDepartment of Preventive Medicine and Epidemiology National Cerebral and Cardiovascular Center Osaka JapanDepartment of Molecular Innovation in Lipidology National Cerebral and Cardiovascular Center Osaka JapanDepartment of Molecular Innovation in Lipidology National Cerebral and Cardiovascular Center Osaka JapanDepartment of Molecular Innovation in Lipidology National Cerebral and Cardiovascular Center Osaka JapanDepartment of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka JapanDepartment of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka JapanDepartment of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka JapanDepartment of Cardiovascular Medicine Graduate School of Medical Sciences Kumamoto University JapanDepartment of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka JapanBackground 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 <15%. The relationship between each PCSK9 subtype level and hyporesponse to statins was investigated. Statins significantly lowered LDL cholesterol level (percent reduction, 40%±21%), whereas 11% of study participants exhibited a hyporeseponse to statins. Multivariable logistic regression analysis demonstrated that baseline mature PCSK9 level was an independent predictor for hyporesponse to statins even after adjusting clinical characteristics (mature PCSK9 per 10‐ng/mL increase: odds ratio [OR], 1.12; 95% CI, 1.01–1.24 [P=0.03]), whereas furin‐cleaved level was not (per 10‐ng/mL increase: OR, 1.37; 95% CI, 0.73–2.58 [P=0.33]). Receiver operating characteristic curve analysis identified mature PCSK9 level of 228 ng/mL as an optimal cutoff to predict hyporesponse to statins (area under the curve, 0.73 [sensitivity, 0.91; specificity, 0.56]). Conclusions Baseline mature PCSK9 level >228 ng/mL is associated with hyporesponse to statins. This finding suggests that mature PCSK9 might be a potential determinant of hyporesponse to statins.https://www.ahajournals.org/doi/10.1161/JAHA.120.019525LDL‐Cproprotein convertase subxilisin/kexin type 9statin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Naoto Kuyama Yu Kataoka Misa Takegami Kunihiro Nishimura Mariko Harada‐Shiba Mika Hori Masatsune Ogura Fumiyuki Otsuka Yasuhide Asaumi Teruo Noguchi Kenichi Tsujita Satoshi Yasuda |
spellingShingle |
Naoto Kuyama Yu Kataoka Misa Takegami Kunihiro Nishimura Mariko Harada‐Shiba Mika Hori Masatsune Ogura Fumiyuki Otsuka Yasuhide Asaumi Teruo Noguchi Kenichi Tsujita Satoshi Yasuda Circulating Mature PCSK9 Level Predicts Diminished Response to Statin Therapy Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease LDL‐C proprotein convertase subxilisin/kexin type 9 statin |
author_facet |
Naoto Kuyama Yu Kataoka Misa Takegami Kunihiro Nishimura Mariko Harada‐Shiba Mika Hori Masatsune Ogura Fumiyuki Otsuka Yasuhide Asaumi Teruo Noguchi Kenichi Tsujita Satoshi Yasuda |
author_sort |
Naoto Kuyama |
title |
Circulating Mature PCSK9 Level Predicts Diminished Response to Statin Therapy |
title_short |
Circulating Mature PCSK9 Level Predicts Diminished Response to Statin Therapy |
title_full |
Circulating Mature PCSK9 Level Predicts Diminished Response to Statin Therapy |
title_fullStr |
Circulating Mature PCSK9 Level Predicts Diminished Response to Statin Therapy |
title_full_unstemmed |
Circulating Mature PCSK9 Level Predicts Diminished Response to Statin Therapy |
title_sort |
circulating mature pcsk9 level predicts diminished response to statin therapy |
publisher |
Wiley |
series |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
issn |
2047-9980 |
publishDate |
2021-06-01 |
description |
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 <15%. The relationship between each PCSK9 subtype level and hyporesponse to statins was investigated. Statins significantly lowered LDL cholesterol level (percent reduction, 40%±21%), whereas 11% of study participants exhibited a hyporeseponse to statins. Multivariable logistic regression analysis demonstrated that baseline mature PCSK9 level was an independent predictor for hyporesponse to statins even after adjusting clinical characteristics (mature PCSK9 per 10‐ng/mL increase: odds ratio [OR], 1.12; 95% CI, 1.01–1.24 [P=0.03]), whereas furin‐cleaved level was not (per 10‐ng/mL increase: OR, 1.37; 95% CI, 0.73–2.58 [P=0.33]). Receiver operating characteristic curve analysis identified mature PCSK9 level of 228 ng/mL as an optimal cutoff to predict hyporesponse to statins (area under the curve, 0.73 [sensitivity, 0.91; specificity, 0.56]). Conclusions Baseline mature PCSK9 level >228 ng/mL is associated with hyporesponse to statins. This finding suggests that mature PCSK9 might be a potential determinant of hyporesponse to statins. |
topic |
LDL‐C proprotein convertase subxilisin/kexin type 9 statin |
url |
https://www.ahajournals.org/doi/10.1161/JAHA.120.019525 |
work_keys_str_mv |
AT naotokuyama circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT yukataoka circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT misatakegami circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT kunihironishimura circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT marikoharadashiba circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT mikahori circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT masatsuneogura circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT fumiyukiotsuka circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT yasuhideasaumi circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT teruonoguchi circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT kenichitsujita circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy AT satoshiyasuda circulatingmaturepcsk9levelpredictsdiminishedresponsetostatintherapy |
_version_ |
1717379735864999936 |