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Circulating Mature PCSK9 Level Predicts Diminished Response to Statin Therapy
Naoto Kuyama1,2, Yu Kataoka1, Misa Takegami3
1Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka Japan.
Journal of the American Heart Association
|May 17, 2021
Summary
Predicting statin hyporesponse is crucial for cardiovascular health. Baseline mature proprotein convertase subxilisin/kexin type 9 (PCSK9) levels above 228 ng/mL can identify patients with a diminished response to statins.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Pharmacogenomics
Background:
- Statin efficacy in lowering low-density lipoprotein (LDL) cholesterol varies significantly among individuals.
- A diminished response to statins (hyporesponse) is linked to adverse cardiovascular outcomes.
- Current methods for predicting statin hyporesponse are insufficient.
Purpose of the Study:
- To investigate whether proprotein convertase subxilisin/kexin type 9 (PCSK9) subtypes can predict statin hyporesponse.
- To determine the relationship between baseline mature PCSK9 levels and reduced LDL cholesterol reduction with statin therapy.
Main Methods:
- Analysis of 101 statin-naive coronary artery disease patients initiating statin therapy.
- Measurement of PCSK9 subtypes (mature and furin-cleaved) using ELISA at baseline and 1 month post-statin initiation.
- Definition of statin hyporesponse as <15% reduction in LDL cholesterol.
Main Results:
- Statins achieved a 40%±21% reduction in LDL cholesterol, with 11% of patients exhibiting hyporesponse.
- Baseline mature PCSK9 level was an independent predictor of statin hyporesponse (OR, 1.12 per 10-ng/mL increase; P=0.03).
- A mature PCSK9 cutoff of 228 ng/mL optimally predicted hyporesponse (AUC, 0.73; sensitivity, 0.91; specificity, 0.56).
Conclusions:
- Elevated baseline mature PCSK9 levels (>228 ng/mL) are associated with a reduced response to statins.
- Mature PCSK9 may serve as a potential biomarker for identifying statin hyporesponders.
- This finding could lead to personalized statin therapy strategies.
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