Polygenic Risk Score Predicts Sudden Death in Patients With Coronary Disease and Preserved Systolic Function.
Polygenic Risk Score Predicts Sudden Death in Patients With Coronary Disease and Preserved Systolic Function.
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DOI：
10.1016/j.jacc.2022.05.049
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发表时间：
2022-08-30
影响因子：
24
通讯作者：
Albert, Christine M.
中科院分区：
文献类型：
--
作者：
Sandhu, Roopinder K.;Dron, Jacqueline S.;Liu, Yunxian;Moorthy, M. Vinayaga;Chatterjee, Neal A.;Ellinor, Patrick T.;Chasman, Daniel I.;Cook, Nancy R.;V. Khera, Amit;Albert, Christine M.
冠状动脉疾病（CAD）背景下存在猝死和/或猝死（SAD）的家族易感性;然而，对其遗传基础了解甚少。确定CAD全基因组多基因评分（GPSCAD）是否可用于无严重收缩功能障碍的CAD患者的SAD风险分层。在4698名患有CAD和左心室射血分数（LVEF）>30- 35%的欧洲血统的PREDETERMINE参与者中，利用全基因组基因分型生成先前验证的GPSCAD。根据一般人群定义的最高GPSCAD十分位数对人群进行二分，并使用竞争风险分析估计SAD和非SAD的绝对、比例和相对风险。中位随访时间为8.0年，与其余受试者相比，GPSCAD前十分位受试者的绝对SAD风险（8.0%; 95% CI，5.1-12.4 vs 4.8%; 95% CI，3.3 -7.0; p=0.005）和比例SAD风险（29% vs 16%; p=0.0003）升高。在控制LVEF、临床因素和ECG参数后，GPSCAD前十分位数与SAD相关（sHR 1.77; 95% CI，1.23-2.54; p=0.002），但与非SAD无关（sHR 1.00，95% CI 0.80-1.25; p=0.98）（Δ p =0.003）。在多变量模型中添加最高GPSCAD十分位数显著改善了净重新分类指数（连续NRI 14.0%，p=0.024和分类NRI 6.6%，p=0.005），但未改善C指数（C指数差异0.007; p=0.143）。在无严重收缩功能障碍的CAD患者中，高GPSCAD特异性预测SAD，并富集绝对和比例SAD风险，确定可能受益于除颤器治疗的人群。在无严重收缩功能障碍的冠状动脉疾病（CAD）患者中，全基因组CAD多基因评分（GPSCAD）的前十分位数确定了绝对猝死和/或猝死（SAD）风险升高的亚群，其中SAD所致死亡的比例高于队列的其余患者。在控制了射血分数、临床因素和ECG参数后，GPSCAD最高十分位数与SAD相关，但与非SAD无关。总的来说，这些数据表明，GPSCAD可能有助于识别可能受益于除颤器治疗的人群。
A familial predisposition to sudden and/or arrhythmic death (SAD) in the setting of coronary artery disease (CAD) exists; however, the genetic basis is poorly understood. To determine whether a genome-wide polygenic score for CAD (GPSCAD) might have utility in SAD risk stratification in CAD patients without severe systolic dysfunction. A previously validated GPSCAD was generated utilizing genome-wide genotyping in 4698 PREDETERMINE participants of European ancestry with CAD and left ventricular ejection fraction (LVEF)>30–35%. The population was dichotomized according to top GPSCAD decile as defined by the general population, and absolute, proportional, and relative risks for SAD and non-SAD were estimated using competing risk analyses. Over a median follow-up of 8.0 years, participants in the top GPSCAD decile were at elevated absolute SAD risk (8.0%; 95% CI, 5.1–12.4 versus 4.8%; 95% CI,3.3–7.0; p=0.005) and proportional SAD risk (29% vs 16%; p=0.0003) compared to the remainder. After controlling for LVEF, clinical factors, and ECG parameters, the top GPSCAD decile was associated with SAD (sHR1.77; 95% CI, 1.23–2.54; p=0.002) but not non-SAD (sHR 1.00, 95% CI 0.80–1.25; p=0.98) (p for Δ =0.003). The addition of the top GPSCAD decile to the multivariable model significantly improved net reclassification indexes (continuous NRI 14.0%, p=0.024 and categorical NRI 6.6%, p=0.005) but not the C-Index (difference in C-Index 0.007; p=0.143). Among CAD patients without severe systolic dysfunction, high GPSCAD specifically predicted SAD and enriched for both absolute and proportional SAD risk, identifying a population who might benefit from defibrillator therapy. Among coronary artery disease (CAD) patients without severe systolic dysfunction, the top decile of a genome-wide polygenic score for CAD (GPSCAD) identified a subpopulation at elevated absolute sudden and/or arrhythmic death (SAD) risk and in whom the proportion of deaths due to SAD was elevated compared to the remainder of the cohort. After controlling for ejection fraction, clinical factors, and ECG parameters, the top GPSCAD decile was associated with SAD but not non-SAD. These data in aggregate suggest that the GPSCAD might be useful in identifying a population who might benefit from defibrillator therapy.
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影响因子：
37.8
作者：
Newton-Cheh C;Cook NR;VanDenburgh M;Rimm EB;Ridker PM;Albert CM
通讯作者：
Albert CM
全基因组关联研究确定了急性心肌梗死中21q21的易感性基因座。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Arking DE;Junttila MJ;Goyette P;Huertas-Vazquez A;Eijgelsheim M;Blom MT;Newton-Cheh C;Reinier K;Teodorescu C;Uy-Evanado A;Carter-Monroe N;Kaikkonen KS;Kortelainen ML;Boucher G;Lagacé C;Moes A;Zhao X;Kolodgie F;Rivadeneira F;Hofman A;Witteman JC;Uitterlinden AG;Marsman RF;Pazoki R;Bardai A;Koster RW;Dehghan A;Hwang SJ;Bhatnagar P;Post W;Hilton G;Prineas RJ;Li M;Köttgen A;Ehret G;Boerwinkle E;Coresh J;Kao WH;Psaty BM;Tomaselli GF;Sotoodehnia N;Siscovick DS;Burke GL;Marbán E;Spooner PM;Cupples LA;Jui J;Gunson K;Kesäniemi YA;Wilde AA;Tardif JC;O'Donnell CJ;Bezzina CR;Virmani R;Stricker BH;Tan HL;Albert CM;Chakravarti A;Rioux JD;Huikuri HV;Chugh SS
通讯作者：
Chugh SS
影响因子：
37.8
作者：
Fishman GI;Chugh SS;Dimarco JP;Albert CM;Anderson ME;Bonow RO;Buxton AE;Chen PS;Estes M;Jouven X;Kwong R;Lathrop DA;Mascette AM;Nerbonne JM;O'Rourke B;Page RL;Roden DM;Rosenbaum DS;Sotoodehnia N;Trayanova NA;Zheng ZJ
通讯作者：
Zheng ZJ
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ