克隆性血液形成和发生性心力衰竭与保存的喷射分数
Art Schuermans1,2,3, Michael C Honigberg1,2,4, Laura M Raffield5
1Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
JAMA network open
|January 25, 2024
概括
不确定潜力的克隆性血液形成 (CHIP) 与心力衰竭有关. 具体来说,TET2 CHIP是心脏衰竭的独立风险因子,具有保存的喷射分数 (HFpEF),建议新的治疗点.
科学领域:
- 心血管疾病 心血管疾病
- 血液学 血液学 血液学
- 遗传学 是一个遗传学.
背景情况:
- 不确定的潜力 (CHIP) 克隆性造血包括血液造血干细胞中与年龄相关的遗传变化.
- 人们越来越认识到CHIP是各种心血管疾病的危险因素,包括心力衰竭 (HF).
研究的目的:
- 调查CHIP及其亚型与心脏衰竭与保留喷射率 (HFpEF) 和心脏衰竭与减少喷射率 (HFrEF) 之间的关联.
主要方法:
- 一项基于人口的队列研究,利用来自杰克逊心脏研究 (JHS) 和妇女健康倡议 (WHI) 的数据.
- 包括全基因组测序的参与者 (N=8090),在基线没有流行性HF,并对HF判断进行了跟踪.
- 进行了统计分析,包括元分析和多变量调整,以评估危险比率.
主要成果:
- 总体而言,CHIP与事件HFpEF或HFrEF没有显著的关联.
- 在TET2 CHIP中,独立于传统风险因素的事件HFpEF (元分析HR,2.35;P=.003) 与事件HFpEF有显著的关联.
- 在WHI队列中,CHIP含高C反应蛋白 (CRP≥2 mg/L) 与增加HFpEF风险相关 (HR,1.94;P=.007).
结论:
- 有TET2突变的CHIP是发展HFpEF的一个独立风险因素.
- 这些发现突显了CHIP特定亚型在HF病变发生过程中的作用,并可能为HFpEF的有针对性的预防和治疗策略提供信息.
相关概念视频
01:17Pathophysiology of Heart Failure
1.6K
Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
1.6K
01:26Imbalances in Cardiac Output
1.4K
The heart's primary function is to pump blood throughout the body, maintaining a balance between blood sent out (cardiac output) and blood returning (venous return). If this balance is disrupted, it can result in congestive heart failure (CHF), a severe condition where the heart becomes an inefficient pump, leading to inadequate blood circulation.
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
1.4K
01:19Multipotency of Hematopoietic Stem Cells
3.1K
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.1K
01:21Hematopoiesis
5.3K
The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
5.3K
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
431
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
431