Familial Hypercholesterolemia in Patients with Acute Coronary Syndrome: Genetic Insights from EXPLORE-J.
Familial Hypercholesterolemia in Patients with Acute Coronary Syndrome: Genetic Insights from EXPLORE-J.
复制标题
DOI：
10.5551/jat.62989
复制
发表时间：
2022-08-01
影响因子：
4.4
通讯作者：
Arai, Hidenori
中科院分区：
文献类型：
--
作者：
Harada-Shiba, Mariko;Ako, Junya;Hirayama, Atsushi;Nakamura, Masato;Nohara, Atsushi;Sato, Kayoko;Murakami, Yoshitaka;Koshida, Ryusuke;Ozaki, Asuka;Arai, Hidenori
目的：基因检测可明确诊断家族性高胆固醇血症（FH）。然而，基因检测的可及性可能在某些不被视为“标准护理”的国家受到限制，包括日本。此外，在大约30%的患者中无法确定导致FH的突变。方法：EXPLORE-J是一项针对急性冠脉综合征（ACS）患者的多中心、前瞻性、观察性研究。对遗传数据进行分析并判定为致病的、不确定的或不可检测的致病变异。结果：1944例患者中，431例接受了基因筛查。总体而言，大多数患者存在fldlr、LDLRAP1或pcsk9的非致病性变异（n=396, 91.9%）。在25例（5.8%）有致病变异的患者中，dlr基因和pcsk9基因的变异分别出现在10例和15例患者中。10例（2.3%）患者观察到不确定变异。在431例患者中，8例（1.9%）符合日本动脉粥样硬化协会（JAS） 2017年指南的FH诊断标准。纳入遗传数据后，33例（7.7%）患者符合JAS指南。没有患者的FH致病变异符合JAS诊断FH的临床标准。结论：结果显示，日本ACS患者中FH基因突变的发生率较高，JAS 2017指南中FH诊断标准的敏感性较低。这些发现突出了急性期ACS患者FH诊断的困难，并提示基因检测和家族史的重要性。
Aim: Genetic testing can provide a definitive diagnosis of familial hypercholesterolemia (FH). However, accessibility of genetic testing may be limited in certain countries where it is not considered “standard of care,” including Japan. In addition, mutations responsible for FH cannot be identified in approximately 30% of patients. Methods: EXPLORE-J is a multicenter, prospective, observational study of patients presenting with acute coronary syndrome (ACS). The genetic data were analyzed and adjudicated as pathogenic, indeterminate, or nondetectable pathogenic variant. Results: Of 1,944 patients, 431 underwent genetic screening. Overall, most patients had nonpathogenic variants ofLDLR,LDLRAP1, orPCSK9 (n=396, 91.9%). Of the 25 (5.8%) patients with pathogenic variants, variants of theLDLR gene and thePCSK9 gene were seen in 10 and 15 patients, respectively. Indeterminate variants were observed in 10 (2.3%) patients. Of the 431 patients, eight (1.9%) met the criteria for a diagnosis of FH using the Japanese Atherosclerosis Society (JAS) 2017 guidelines. When genetic data were incorporated, 33 (7.7%) patients met the JAS guidelines. No patients with FH pathogenic variants satisfied the JAS clinical criteria for a diagnosis of FH. Conclusions: The results revealed a higher prevalence of genetic mutations of FH among Japanese patients with ACS and a low sensitivity of the FH diagnostic criteria of the JAS 2017 guidelines. These findings highlight the difficulties of FH diagnosis in patients with ACS in the acute phase and suggest the importance of genetic testing and family history.
登录
查看更多内容
影响因子：
3.9
作者：
Marduel, Marie;Carrie, Alain;Rabes, Jean-Pierre
通讯作者：
Rabes, Jean-Pierre
影响因子：
39.3
作者：
Nordestgaard BG;Chapman MJ;Humphries SE;Ginsberg HN;Masana L;Descamps OS;Wiklund O;Hegele RA;Raal FJ;Defesche JC;Wiegman A;Santos RD;Watts GF;Parhofer KG;Hovingh GK;Kovanen PT;Boileau C;Averna M;Borén J;Bruckert E;Catapano AL;Kuivenhoven JA;Pajukanta P;Ray K;Stalenhoef AF;Stroes E;Taskinen MR;Tybjærg-Hansen A;European Atherosclerosis Society Consensus Panel
通讯作者：
European Atherosclerosis Society Consensus Panel
影响因子：
3.7
作者：
Hartgers ML;Ray KK;Hovingh GK
通讯作者：
Hovingh GK
影响因子：
4.4
作者：
Harada T;Inagaki-Tanimura K;Nagao M;Sato Y;Sudo M;Okajima F;Sugihara H;Oikawa S
通讯作者：
Oikawa S
影响因子：
5.8
作者：
Harada-Shiba, M;Takagi, A;Yamamoto, A
通讯作者：
Yamamoto, A