Yang L, Xiao YY, Shao L, Ouyang CS, Hu Y, Li B, Lei LF, Wang H. Proprotein convertase subtilisin/kexin type 9 inhibitor non responses in an adult with a history of coronary revascularization: A case report. World J Clin Cases 2022; 10(19): 6728-6735 [PMID: 35979295 DOI: 10.12998/wjcc.v10.i19.6728]
Corresponding Author of This Article
Hong Wang, MD, Chief Physician, Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, No. 152 Aiguo Road, Donghu District, Nanchang 330006, Jiangxi Province, China. hongwangjx@21cn.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Cases. Jul 6, 2022; 10(19): 6728-6735 Published online Jul 6, 2022. doi: 10.12998/wjcc.v10.i19.6728
Proprotein convertase subtilisin/kexin type 9 inhibitor non responses in an adult with a history of coronary revascularization: A case report
Liu Yang, Yan-Yan Xiao, Liang Shao, Chang-Sheng Ouyang, Yao Hu, Bin Li, Li-Feng Lei, Hong Wang
Liu Yang, Liang Shao, Chang-Sheng Ouyang, Yao Hu, Bin Li, Hong Wang, Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China
Yan-Yan Xiao, Postgraduate School of Jiangxi University of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330008, Jiangxi Province, China
Li-Feng Lei, Department of Internal Medicine, Tonggu People's Hospital, Yichun 336299, Jiangxi Province, China
Author contributions: Shao L and Li B collected all the data; Xiao YY and Ouyang CS recorded the video; Hu Y, Lei LF and Xiao YY performed the literature review; Yang L wrote the manuscript; Wang H reviewed and revised the manuscript; all authors issued final approval for the version to be submitted and provided critical comments in the revision of the article.
Supported bythe Doctor Start-up fund of Jiangxi provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, No. 19-236.
Informed consent statement: Written informed consent for publication was obtained from the whole family.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016). The manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong Wang, MD, Chief Physician, Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, No. 152 Aiguo Road, Donghu District, Nanchang 330006, Jiangxi Province, China. hongwangjx@21cn.com
Received: February 12, 2022 Peer-review started: February 12, 2022 First decision: March 25, 2022 Revised: April 7, 2022 Accepted: April 30, 2022 Article in press: April 30 2022 Published online: July 6, 2022 Processing time: 131 Days and 23.5 Hours
Abstract
BACKGROUND
Familial hypercholesterolemia (FH) is an autosomal dominant disorder that is characterized by severely increased low-density lipoprotein (LDL) cholesterol levels. At the same time, elevated LDL levels accelerated the development of coronary heart disease. Several classes of drugs are currently in use to treat FH. Proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is novel one of these.
CASE SUMMARY
This manuscript reports a case of FH that responded modestly after treatment with PCSK9i and statin drugs. Of even more concern is that the patient frequently admitted to the hospital during a 12-year follow-up period. Subsequently, we identified a heterozygous mutation, 1448G>A (W483X) of the LDL receptor (LDLR) in this patient. The serum levels of PCSK9 (proprotein convertase subtilisin/kexin type 9) in the patient was 71.30 ± 26.66 ng/mL, which is close the average level reported in the literature. This LDLR mutation affects LDLR metabolism or structure, which may make it unsuitable for use of PCSK9i.
CONCLUSION
Our outcome demonstrates that LDLR-W483X represents a partial loss-of-function LDLR and may contribute to PCSK9i ineffective. In the meanwhile, additional measures are therefore required (particularly with gene sequencing or change the treatment plan) must be initiated as early as possible. Genetic testing for clinically challenging cases who do not respond to PCSK9i therapy is very helpful.
Core Tip: We report a male Chinese patient diagnosed with Familial hypercholesterolemia with a heterozygous mutation, 1448G>A (W483X), of the low-density lipoprotein receptor (LDLR). By reviewing the literature, we speculate that the mutation may affect LDLR metabolism or structure and may lead to that responded modestly after treatment with Proprotein convertase subtilisin/kexin type 9 inhibitor.
