Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease.
Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease.
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DOI：
10.1016/j.jacc.2023.03.401
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发表时间：
2023-05-23
影响因子：
24
通讯作者：
Honigberg, Michael C.
中科院分区：
文献类型：
--
作者：
Gumuser, Esra D.;Schuermans, Art;Cho, So Mi Jemma;Sporn, Zachary A.;Uddin, Md Mesbah;Paruchuri, Kaavya;Nakao, Tetsushi;Yu, Zhi;Haidermota, Sara;Hornsby, Whitney;Weeks, Lachelle D.;Niroula, Abhishek;Jaiswal, Siddhartha;Libby, Peter;Ebert, Benjamin L.;Bick, Alexander G.;Natarajan, Pradeep;Honigberg, Michael C.
不确定潜能的克隆性造血（CHIP）-具有白血病相关突变的血液干细胞的年龄相关克隆性扩增-是一种新的心血管危险因素。CHIP是否在已确诊的动脉粥样硬化性心血管疾病（ASCVD）患者中具有预后意义尚不清楚。这项研究测试了CHIP是否预测了确诊ASCVD患者的不良结局。分析了来自英国生物库的年龄在40至70岁之间的具有已建立的ASCVD和可用的全外显子组序列的个体。主要结局是ASCVD事件和全因死亡率的复合终点。使用未校正和多变量校正的考克斯回归，比较任何CHIP（变异等位基因分数≥2%）、大CHIP克隆（变异等位基因分数≥10%）和最常见突变驱动基因（DNMT 3A、TET 2、ASXL 1、JAK 2、PPM 1D/TP 53 [DNA损伤修复基因]和SF 3B 1/SRSF 2/U2 AF 1 [剪接体基因]）与事件结局的关联。在纳入的13，129名个体（中位年龄：63岁）中，665名（5.1%）患有CHIP。在中位随访10.8年期间，基线时任何CHIP和大CHIP与主要结局的调整后HR分别为1.23（95%CI：1.10-1.38; P < 0.001）和1.34（95%CI：1.17-1.53; P < 0.001）相关。TET 2和剪接体CHIP，尤其是大克隆，与不良结局的相关性最强（大TET 2 CHIP：HR：1.89; 95%CI：1.40-2.55; P <0.001;大剪接体CHIP：HR：3.02; 95%CI：1.95-4.70; P < 0.001）。CHIP与ASCVD患者的不良结局独立相关，TET 2和SF 3B 1/SRSF 2/U2 AF 1 CHIP中观察到的风险尤其高。
Clonal hematopoiesis of indeterminate potential (CHIP)–the age-related clonal expansion of blood stem cells with leukemia-associated mutations–is a novel cardiovascular risk factor. Whether CHIP remains prognostic in individuals with established atherosclerotic cardiovascular disease (ASCVD) is less clear. This study tested whether CHIP predicts adverse outcomes in individuals with established ASCVD. Individuals aged 40 to 70 years from the UK Biobank with established ASCVD and available whole-exome sequences were analyzed. The primary outcome was a composite of ASCVD events and all-cause mortality. Associations of any CHIP (variant allele fraction ≥2%), large CHIP clones (variant allele fraction ≥10%), and the most commonly mutated driver genes (DNMT3A, TET2, ASXL1, JAK2, PPM1D/TP53 [DNA damage repair genes], and SF3B1/SRSF2/U2AF1 [spliceosome genes]) with incident outcomes were compared using unadjusted and multivariable-adjusted Cox regression. Of 13,129 individuals (median age: 63 years) included, 665 (5.1%) had CHIP. Over a median follow-up of 10.8 years, any CHIP and large CHIP at baseline were associated with adjusted HRs of 1.23 (95% CI: 1.10-1.38; P < 0.001) and 1.34 (95% CI: 1.17-1.53; P < 0.001), respectively, for the primary outcome. TET2 and spliceosome CHIP, especially large clones, were most strongly associated with adverse outcomes (large TET2 CHIP: HR: 1.89; 95% CI: 1.40-2.55; P <0.001; large spliceosome CHIP: HR: 3.02; 95% CI: 1.95-4.70; P < 0.001). CHIP is independently associated with adverse outcomes in individuals with established ASCVD, with especially high risks observed in TET2 and SF3B1/SRSF2/U2AF1 CHIP.
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影响因子：
64.8
作者：
Bick AG;Weinstock JS;Nandakumar SK;Fulco CP;Bao EL;Zekavat SM;Szeto MD;Liao X;Leventhal MJ;Nasser J;Chang K;Laurie C;Burugula BB;Gibson CJ;Lin AE;Taub MA;Aguet F;Ardlie K;Mitchell BD;Barnes KC;Moscati A;Fornage M;Redline S;Psaty BM;Silverman EK;Weiss ST;Palmer ND;Vasan RS;Burchard EG;Kardia SLR;He J;Kaplan RC;Smith NL;Arnett DK;Schwartz DA;Correa A;de Andrade M;Guo X;Konkle BA;Custer B;Peralta JM;Gui H;Meyers DA;McGarvey ST;Chen IY;Shoemaker MB;Peyser PA;Broome JG;Gogarten SM;Wang FF;Wong Q;Montasser ME;Daya M;Kenny EE;North KE;Launer LJ;Cade BE;Bis JC;Cho MH;Lasky-Su J;Bowden DW;Cupples LA;Mak ACY;Becker LC;Smith JA;Kelly TN;Aslibekyan S;Heckbert SR;Tiwari HK;Yang IV;Heit JA;Lubitz SA;Johnsen JM;Curran JE;Wenzel SE;Weeks DE;Rao DC;Darbar D;Moon JY;Tracy RP;Buth EJ;Rafaels N;Loos RJF;Durda P;Liu Y;Hou L;Lee J;Kachroo P;Freedman BI;Levy D;Bielak LF;Hixson JE;Floyd JS;Whitsel EA;Ellinor PT;Irvin MR;Fingerlin TE;Raffield LM;Armasu SM;Wheeler MM;Sabino EC;Blangero J;Williams LK;Levy BD;Sheu WH;Roden DM;Boerwinkle E;Manson JE;Mathias RA;Desai P;Taylor KD;Johnson AD;NHLBI Trans-Omics for Precision Medicine Consortium;Auer PL;Kooperberg C;Laurie CC;Blackwell TW;Smith AV;Zhao H;Lange E;Lange L;Rich SS;Rotter JI;Wilson JG;Scheet P;Kitzman JO;Lander ES;Engreitz JM;Ebert BL;Reiner AP;Jaiswal S;Abecasis G;Sankaran VG;Kathiresan S;Natarajan P
通讯作者：
Natarajan P
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
影响因子：
20.1
作者：
North BJ;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
30.8
作者：
Kar, Siddhartha P.;Quiros, Pedro M.;Gu, Muxin;Jiang, Tao;Mitchell, Jonathan;Langdon, Ryan;Iyer, Vivek;Barcena, Clea;Vijayabaskar, M. S.;Fabre, Margarete A.;Carter, Paul;Petrovski, Slave;Burgess, Stephen;Vassiliou, George S.
通讯作者：
Vassiliou, George S.