Reiner Alex P, Roberts Mary B, Honigberg Michael C, Kooperberg Charles, Desai Pinkal, Bick Alexander G, Natarajan Pradeep, Manson JoAnn E, Whitsel Eric A, Eaton Charles B
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington.
Center for Primary Care and Prevention, Brown University, Pawtucket, Rhode Island.
medRxiv. 2023 Jun 10:2023.06.07.23291038. doi: 10.1101/2023.06.07.23291038.
Clonal hematopoiesis of indeterminate potential (CHIP) was recently identified as a risk factor for incident heart failure (HF). Whether CHIP is associated selectively with risk of heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) subtypes is unknown.
To evaluate whether CHIP is associated with incident HF subtypes, HFrEF versus HFpEF.
We obtained CHIP status from whole genome sequencing of blood DNA in participants without prevalent HF from a multi-ethnic sample of post-menopausal women without prevalent HF (N=5,214) from the Women's Health Initiative (WHI). Cox proportional hazards models were performed, adjusting for demographic and clinical risk factors.
CHIP was significantly associated with a 42% (95%CI 6%, 91%) increased risk of HFpEF (P=0.02). In contrast, there was no evidence of association between CHIP and risk of incident HFrEF. When the three most common CHIP subtypes were assessed individually, the risk of HFpEF was more strongly associated with TET2 (HR=2.5; 95%CI 1.54, 4.06; P<0.001), than DNMT3A or ASXL1.
CHIP, particularly mutations in represents a potential new risk factor for incident HFpEF.
不确定潜能的克隆性造血（CHIP）最近被确定为新发心力衰竭（HF）的一个危险因素。CHIP是否与射血分数降低的心力衰竭（HFrEF）或射血分数保留的心力衰竭（HFpEF）亚型的风险选择性相关尚不清楚。
评估CHIP是否与新发HF亚型（HFrEF与HFpEF）相关。
我们从女性健康倡议（WHI）中无HF病史的绝经后女性多民族样本（N = 5214）的血液DNA全基因组测序中获得CHIP状态。进行Cox比例风险模型分析，并对人口统计学和临床危险因素进行校正。
CHIP与HFpEF风险显著增加42%（95%CI 6%，91%）相关（P = 0.02）。相比之下，没有证据表明CHIP与新发HFrEF风险之间存在关联。当单独评估三种最常见的CHIP亚型时，HFpEF风险与TET2的相关性更强（HR = 2.5；95%CI 1.54，4.06；P < 0.001），高于DNMT3A或ASXL1。
CHIP，特别是 中的突变代表了新发HFpEF的一个潜在新危险因素。
