著者

Anthony C. Keech Kazuma Oyama Peter S. Sever Minao Tang Sabina A. Murphy Atsushi Hirayama Chen Lu Leslie Tay Prakash C. Deedwania Chung-Wah Siu Armando Lira Pineda Donghoon Choi Min-Ji Charng John Amerena Wan Azman Wan Ahmad Vijay K. Chopra Terje R. Pedersen Robert P. Giugliano Marc S. Sabatine on behalf of the FOURIER Study Group

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-20-1051, (Released:2021-05-12)

参考文献数

19

被引用文献数

13

---

Background:There are concerns that Asian patients respond differently to some medications. This study evaluated the efficacy and safety of evolocumab among Asian vs. other subjects in the FOURIER trial, which randomized stable atherosclerosis patients to receive either evolocumab or placebo.Methods and Results:Effects of adding evolocumab vs. placebo to background statin therapy on low-density lipoprotein cholesterol (LDL-C) reductions, cardiovascular outcomes, and adverse events were compared among 27,564 participants with atherosclerotic disease, according to self-reported Asian (n=2,723) vs. other (n=24,841) races followed for a median of 2.2 years in the FOURIER trial. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. At randomization, Asians had slightly lower LDL-C (median 89 [IQR 78–104] mg/dL vs. 92 [80–109] mg/dL; P<0.001) and were much less likely to be on a high-intensity statin (33.3% vs. 73.3%; P<0.001). Evolocumab lowered LDL-C more in Asians than in others (66% vs. 58%; P<0.001). The effect of evolocumab on the primary endpoint was similar in Asians (HR, 0.79; 95% CI, 0.61–1.03) and others (HR, 0.86; 95% CI, 0.79–0.93; P interaction=0.55). There was no excess of serious adverse events with evolocumab among Asians over others.Conclusions:Use of evolocumab robustly lowers LDL-C and is equally efficacious in lowering the risk of cardiovascular events and safe in Asians as it is in others.

著者

Kuan-Rau Chiou Chung-Yung Chen Min-ji Charng

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.29736, (Released:2015-04-04)

参考文献数

41

被引用文献数

2 5

---

Aim: Whole exome sequencing (WES) is a recently developed method for discovering rare mutations associated with hereditary disorders. However, the feasibility and utilization of this method in identifying familial hypertriglyceridemia is not well known. The purpose of the study was to identify the genetic locus that causes hypertriglyceridemia and assess its prevalence in Taiwanese subjects with hypertriglyceridemia.Methods: We performed WES among two individuals with hypertriglyceridemia and one control subject in an index family (22 members). Based on the WES findings, we extended the study to genotype 65 unrelated adult index patients with a fasting serum triglyceride level of >500 mg/dL and 125 normal controls using polymerase chain reaction.Results: Using WES alignment, variant calling and annotation, 15 presumptive causal variants were initially identified, including 13 cases by the autosomal dominant model and two cases by the autosomal recessive model. Only APOA5 c.553 G>T (rs2075291), resulting in the amino acid mutation Gly185Cys, co-segregated well with hypertriglyceridemia in terms of autosomal recessive inheritance (homozygote TT: mean triglyceride level: 1,071 mg/dL vs non TT (GT and GG): mean triglyceride level: 118 mg/dL; p<0.001) in the index family. In the unrelated cohorts, the frequency of the TT genotype of rs2075291 was 12.3% in the hypertriglyceridemic group; however, no TT genotype was found in the control group.Conclusions: Our results demonstrate that WES is feasible for identifying the genetic locus that causes hypertriglyceridemia. The TT genotype of APOA5 c.553G>T acts as an important indicator of hypertriglyceridemia in patients in Taiwan.