Cardiovascular Disease Among Patients With AML and CHIP-Related Mutations.
Cardiovascular Disease Among Patients With AML and CHIP-Related Mutations.
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DOI：
10.1016/j.jaccao.2021.11.008
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发表时间：
2022-03
影响因子：
11.1
通讯作者：
Thavendiranathan, Paaladinesh
中科院分区：
文献类型：
--
作者：
Calvillo-Arguelles, Oscar;Schoffel, Alice;Capo-Chichi, Jose-Mario;Abdel-Qadir, Husam;Schuh, Andre;Carrillo-Estrada, Montserrat;Liu, Shiying;Gupta, Vikas;Schimmer, Aaron D.;Yee, Karen;Shlush, Liran, I;Natarajan, Pradeep;Thavendiranathan, Paaladinesh
关键词：
不确定潜能的克隆性造血（CHIP）是非急性髓系白血病（AML）个体中一种新的心血管疾病（CVD）危险因素。本研究的目的是检查AML诊断患者中确定的CHIP相关突变（CHIP相关突变）与心血管事件（CVEs）风险之间的相关性。这是一项回顾性队列研究，纳入了2015年至2018年间接受DNA分析的623例AML患者。使用原因特异性风险回归模型研究常见CHIP相关基因（DNMT 3A、TET 2、ASXL 1、JAK 2、TP 53、SRSF 2和SF 3B 1）的致病性突变与CVE（心力衰竭住院、急性冠状动脉综合征、冠状动脉血运重建、缺血性卒中、静脉血栓栓塞和CVD死亡）发生率之间的关联，以及CVE发生与全因死亡率之间的关联。患者年龄为64.6 ± 15.3岁，265例（42.5%）为女性，63%至少有1个CHIP相关突变。CHIP相关突变的患者年龄较大（69.2 ± 12.3 vs 56.6 ± 16.6岁; P < 0.001），CVD危险因素和CVD病史的患病率较高。在校正分析中，任何CHIP相关突变的存在与强化治疗患者（基于蒽环类药物）中较高的CVE发生率相关（HR：1.74; 95% CI：1.03-2.93; P = 0.037），但与整个队列无关（HR：1.26; 95% CI：0.81-1.97; P = 0.31）。TP53（HR：4.18; 95% CI：2.07-8.47; P < 0.001）和ASXL 1（HR：2.37; 95%CI：1.21-4.63; P = 0.012）突变与强化治疗患者的CVE相关。周期性心血管事件的发生与全因死亡率相关（HR：1.99; 95%CI：1.45-2.73; P < 0.001）。在接受强化化疗的AML患者中，CHIP相关基因突变与AML诊断后发生偶发性CVE的风险增加相关。
Clonal hematopoiesis of indeterminate potential (CHIP) is a novel cardiovascular disease (CVD) risk factor in individuals without acute myeloid leukemia (AML). The aim of this study was to examine the association between mutations associated with CHIP (CHIP-related mutations) identified in patients at AML diagnosis and the risk for cardiovascular events (CVEs). This was a retrospective cohort study of 623 patients with AML treated between 2015 and 2018 who underwent DNA analysis. Cause-specific hazard regression models were used to study the associations between pathogenic mutations in common CHIP-related genes (DNMT3A, TET2, ASXL1, JAK2, TP53, SRSF2, and SF3B1) and the rate of CVEs (heart failure hospitalization, acute coronary syndrome, coronary artery revascularization, ischemic stroke, venous thromboembolism, and CVD death) and between CVE development and all-cause mortality. Patients were 64.6 ± 15.3 years of age, 265 (42.5%) were women, and 63% had at least 1 CHIP-related mutation. Those with CHIP-related mutations were older (69.2 ± 12.3 vs 56.6 ± 16.6 years; P < 0.001) and had a greater prevalence of CVD risk factors and CVD history. In adjusted analysis, the presence of any CHIP-related mutation was associated with a higher rate of CVEs (HR: 1.74; 95% CI: 1.03-2.93; P = 0.037) among intensively treated patients (anthracycline based) but not the whole cohort (HR: 1.26; 95% CI: 0.81-1.97; P = 0.31). TP53 (HR: 4.18; 95% CI: 2.07-8.47; P < 0.001) and ASXL1 (HR: 2.37; 95% CI: 1.21-4.63; P = 0.012) mutations were associated with CVEs among intensively treated patients. Interval development of CVEs was associated with all-cause mortality (HR: 1.99; 95% CI: 1.45-2.73; P < 0.001). Among patients with AML treated with intensive chemotherapy, mutations in CHIP-related genes were associated with an increased risk for developing incident CVEs after AML diagnosis.
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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
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
在健康个体中预测急性髓样白血病的风险。
影响因子：
64.8
作者：
Abelson S;Collord G;Ng SWK;Weissbrod O;Mendelson Cohen N;Niemeyer E;Barda N;Zuzarte PC;Heisler L;Sundaravadanam Y;Luben R;Hayat S;Wang TT;Zhao Z;Cirlan I;Pugh TJ;Soave D;Ng K;Latimer C;Hardy C;Raine K;Jones D;Hoult D;Britten A;McPherson JD;Johansson M;Mbabaali F;Eagles J;Miller JK;Pasternack D;Timms L;Krzyzanowski P;Awadalla P;Costa R;Segal E;Bratman SV;Beer P;Behjati S;Martincorena I;Wang JCY;Bowles KM;Quirós JR;Karakatsani A;La Vecchia C;Trichopoulou A;Salamanca-Fernández E;Huerta JM;Barricarte A;Travis RC;Tumino R;Masala G;Boeing H;Panico S;Kaaks R;Krämer A;Sieri S;Riboli E;Vineis P;Foll M;McKay J;Polidoro S;Sala N;Khaw KT;Vermeulen R;Campbell PJ;Papaemmanuil E;Minden MD;Tanay A;Balicer RD;Wareham NJ;Gerstung M;Dick JE;Brennan P;Vassiliou GS;Shlush LI
通讯作者：
Shlush LI
影响因子：
6.6
作者：
Alduaij, Waleed;McNamara, Caroline J.;Gupta, Vikas
通讯作者：
Gupta, Vikas
影响因子：
82.9
作者：
Guryanova OA;Shank K;Spitzer B;Luciani L;Koche RP;Garrett-Bakelman FE;Ganzel C;Durham BH;Mohanty A;Hoermann G;Rivera SA;Chramiec AG;Pronier E;Bastian L;Keller MD;Tovbin D;Loizou E;Weinstein AR;Gonzalez AR;Lieu YK;Rowe JM;Pastore F;McKenney AS;Krivtsov AV;Sperr WR;Cross JR;Mason CE;Tallman MS;Arcila ME;Abdel-Wahab O;Armstrong SA;Kubicek S;Staber PB;Gönen M;Paietta EM;Melnick AM;Nimer SD;Mukherjee S;Levine RL
通讯作者：
Levine RL