Clonal Hematopoiesis and Incident Heart Failure With Preserved Ejection Fraction.
Clonal Hematopoiesis and Incident Heart Failure With Preserved Ejection Fraction.
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DOI：
10.1001/jamanetworkopen.2023.53244
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发表时间：
2024-01-02
影响因子：
13.8
通讯作者：
Reiner, Alexander P.
中科院分区：
文献类型：
--
作者：
Schuermans, Art;Honigberg, Michael C.;Raffield, Laura M.;Yu, Bing;Roberts, Mary B.;Kooperberg, Charles;Desai, Pinkal;Carson, April P.;Shah, Amil M.;Ballantyne, Christie M.;Bick, Alexander G.;Natarajan, Pradeep;Manson, JoAnn E.;Whitsel, Eric A.;Eaton, Charles B.;Reiner, Alexander P.
不确定潜能的克隆造血（CHIP）或某些CHIP驱动基因是否与特定的心力衰竭（HF）亚型相关？在这项由2个种族多样的队列共包括8090名参与者的队列研究中，TET 2 CHIP与射血分数保留的HF事件风险高2.4倍独立相关。相比之下，CHIP与射血分数降低的HF事件无显著相关性。这些结果表明TET 2 CHIP是与射血分数保留的HF事件相关的风险因素。本队列研究评估了不确定潜能的克隆性造血（CHIP）和关键基因特异性CHIP亚型与射血分数保留和降低的心力衰竭事件的潜在相关性。不确定潜能的克隆性造血（CHIP），即具有致白血病获得性遗传变异的造血干细胞的年龄相关性克隆扩增，与心力衰竭（HF）相关。评估CHIP和关键基因特异性CHIP亚型与射血分数保留（HFpEF）和射血分数降低（HFrEF）的HF事件的相关性。这项基于人群的队列研究纳入了来自2项具有统一HF亚型裁定的种族多样性前瞻性队列研究的受试者：杰克逊心脏研究（JHS）和妇女健康倡议（WHI）。JHS参与者于2000年至2004年期间入组，并随访至2016年。WHI参与者于1993年至1998年期间入组，并随访至2022年。纳入了接受全基因组测序、基线时无流行性HF且随访HF判定的参与者。JHS和WHI的随访时间中位数（IQR）分别为12.0（11.0-12.0）年和15.3（9.0-22.0）年。于二零二三年六月至十二月进行统计分析。任何CHIP和最常见的基因特异性CHIP亚型（DNMT 3A和TET 2 CHIP）。根据医院记录裁定首次住院HF事件，并将其分类为HFpEF（左心室射血分数≥50%）或HFrEF（射血分数<50%）。共纳入8090名参与者; 2927名来自JHS（中位[IQR]年龄，56 [46-65]岁; 1846 [63.1%]女性; 2927 [100.0%]黑人或非裔美国人）和5163例来自WHI（中位数[IQR]年龄，67 [62-72]岁; 5163 [100.0%]女性; 29 [0.6%]美洲印第安人或阿拉斯加原住民，37 [0.7%]亚洲或太平洋岛民，1383 [26.8%]黑人或非裔美国人，293 [5.7%]西班牙裔或拉丁裔，3407例[66.0%]非西班牙裔白色，14例[0.3%]其他人种和种族）。复合CHIP和HFpEF的多变量校正风险比（HR）为1.28（95% CI，0.93-1.76; P = 0.13），CHIP和HFrEF的多变量校正风险比（HR）为0.79（95% CI，0.49-1.25; P = 0.31）。TET 2 CHIP与两个队列中的HFpEF相关（荟萃分析HR，2.35 [95% CI，1.34 - 4.11]; P = .003），与心血管风险因素和冠状动脉疾病无关。WHI中按C反应蛋白（CRP）分层的分析发现，CHIP和CRP ≥ 2 mg/L的个体发生HFpEF的风险增加（HR，1.94 [95% CI，1.20-3.15]; P = 0.007），但在CHIP和CRP低于2 mg/L或CRP大于或等于2 mg/L而无CHIP的患者中，与无CHIP且CRP低于2 mg/L的受试者相比。在这项队列研究中，TET 2 CHIP是与HFpEF事件相关的独立风险因素。这一发现可能对HFpEF的预防和管理产生影响，包括靶向治疗的开发。
Are clonal hematopoiesis of indeterminate potential (CHIP) or certain CHIP driver genes associated with a specific heart failure (HF) subtype? In this cohort study of 2 racially diverse cohorts collectively including 8090 participants, TET2 CHIP was independently associated with a 2.4-fold higher risk of incident HF with preserved ejection fraction. By contrast, there were no significant associations of CHIP with incident HF with reduced ejection fraction. These results suggest that TET2 CHIP is a risk factor associated with incident HF with preserved ejection fraction. This cohort study evaluates the potential associations of clonal hematopoiesis of indeterminate potential (CHIP) and key gene-specific CHIP subtypes with incident heart failure with preserved and reduced ejection fraction. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic stem cells with leukemogenic acquired genetic variants, is associated with incident heart failure (HF). To evaluate the associations of CHIP and key gene-specific CHIP subtypes with incident HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). This population-based cohort study included participants from 2 racially diverse prospective cohort studies with uniform HF subtype adjudication: the Jackson Heart Study (JHS) and Women’s Health Initiative (WHI). JHS participants were enrolled during 2000 to 2004 and followed up through 2016. WHI participants were enrolled during 1993 to 1998 and followed up through 2022. Participants who underwent whole-genome sequencing, lacked prevalent HF at baseline, and were followed up for HF adjudication were included. Follow-up occurred over a median (IQR) of 12.0 (11.0-12.0) years in the JHS and 15.3 (9.0-22.0) years in the WHI. Statistical analysis was performed from June to December 2023. Any CHIP and the most common gene-specific CHIP subtypes (DNMT3A and TET2 CHIP). First incident hospitalized HF events were adjudicated from hospital records and classified as HFpEF (left ventricular ejection fraction ≥50%) or HFrEF (ejection fraction <50%). A total of 8090 participants were included; 2927 from the JHS (median [IQR] age, 56 [46-65] years; 1846 [63.1%] female; 2927 [100.0%] Black or African American) and 5163 from the WHI (median [IQR] age, 67 [62-72] years; 5163 [100.0%] female; 29 [0.6%] American Indian or Alaska Native, 37 [0.7%] Asian or Pacific Islander, 1383 [26.8%] Black or African American, 293 [5.7%] Hispanic or Latinx, 3407 [66.0%] non-Hispanic White, and 14 [0.3%] with other race and ethnicity). The multivariable-adjusted hazard ratio (HR) for composite CHIP and HFpEF was 1.28 (95% CI, 0.93-1.76; P = .13), and for CHIP and HFrEF it was 0.79 (95% CI, 0.49-1.25; P = .31). TET2 CHIP was associated with HFpEF in both cohorts (meta-analyzed HR, 2.35 [95% CI, 1.34 to 4.11]; P = .003) independent of cardiovascular risk factors and coronary artery disease. Analyses stratified by C-reactive protein (CRP) in the WHI found an increased risk of incident HFpEF in individuals with CHIP and CRP greater than or equal to 2 mg/L (HR, 1.94 [95% CI, 1.20-3.15]; P = .007), but not in those with CHIP and CRP less than 2 mg/L or those with CRP greater than or equal to 2 mg/L without CHIP, when compared with participants without CHIP and CRP less than 2 mg/L. In this cohort study, TET2 CHIP was an independent risk factor associated with incident HFpEF. This finding may have implications for the prevention and management of HFpEF, including development of targeted therapies.
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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：
13.8
作者：
Hansen AL;Søndergaard MM;Hlatky MA;Vittinghof E;Nah G;Stefanick ML;Manson JE;Farland LV;Wells GL;Mongraw-Chaffin M;Gunderson EP;Van Horn L;Wild RA;Liu B;Shadyab AH;Allison MA;Liu S;Eaton CB;Honigberg MC;Parikh NI
通讯作者：
Parikh NI
影响因子：
24
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.
通讯作者：
Honigberg, Michael C.
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
影响因子：
24
作者：
Sano S;Oshima K;Wang Y;MacLauchlan S;Katanasaka Y;Sano M;Zuriaga MA;Yoshiyama M;Goukassian D;Cooper MA;Fuster JJ;Walsh K
通讯作者：
Walsh K