坂井 晶子
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Assistant Professor
Language English
Title Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK-9) Inhibitor Improve Lipid Profile and Vascular Atherosclerotic Plaque Formation in Japanese High-Risk Familia Hypercholesterolemia
Conference American Heart Association (AHA) Scientific Sessions 2018
Promoters American Heart Association (AHA)
Conference Type International society and overseas society
Presentation Type Poster notice
Lecture Type General
Publisher and common publisher◎ABE Takuro, SATO Kayoko, IMAMURA Yasutaka, YAMAMOTO Eri, MATSUURA Junya, NOMURA Hidekimi, SAKAI Akiko, SEKIGUCHI Haruki, HAGIWARA Nobuhisa
Date 2018/11/12
Venue
(city and name of the country)
Chicago, USA
Summary *Session Title: Lipids and Lipoprotein Metabolism

Introduction: The effectiveness of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors in patients with ischemic heart disease was revealed by FOURIER and GLAGOV trials. For secondary prevention, low-density lipoprotein cholesterol (LDL-C) levels should be controlled below 70mg/dL. However, for the patients with heterozygous familial hypercholesterolemia (heFH), it is difficult to reach the target levels of LDL-C with conventional hypolipidemic drugs.

Hypothesis: PCSK-9 inhibitors rapidly improve the levels of LDL-C and the atherosclerosis in heFH patients with high risk.

Methods: We examined the effects of PCSK-9 inhibitors in the high-risk heFH patients. From 2016, we selected the patients with heFH had multiple risk factors, such as the past history of CVD, Age>35 years (men) and >45 years (women), TG>150mg/dl, HDL-C<40mg/dl, LP(a)>50mg/dl, achilles tendon xanthoma (ATX)>15mm, current smoker, DM, Hypertension, or CKD. Furthermore, we administered PCSK-9 inhibitors to the patients could not achieve the ideal LCL-C levels treated with the maximum dose of statin. We analyzed the clinical course for first and second prevention, clinical characteristics, biochemical data, physiological examination, and gene mutation in the consecutive 30 high-risk heFH patients (16 men and 14 women).

Results: The age of heFH patients was 59.4±13.2 years and BMI was 26.9±4.1 kg/m2. We examined the gene mutation in 17 patients with heFH, and found 8 of LDLR and 4 of PCSK-9 gene mutations, and 3 of those had double heterozygous mutations. Therefore, the many heFH patients with high risk had the genetic mutation, and had more atherosclerotic developments. The T-cho, LDL-C, ApoB, LP(a), and oxidized LDL-C were improved significantly after PCSK-9 inhibitor treatments within 4 weeks. In many cases, the maximum carotid artery intima-media thickness (IMT) and ATX, and coronary artery plaques were decreased dramatically after 24W.

Conclusions: The plaque formation in high-risk heFH patients was improved following strong lipids-lowering effects by PCSK-9 inhibitor, it could be prevented the future cardiovascular events.