期刊
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
卷 74, 期 4, 页码 578-586出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2019.05.045
关键词
aging; atherosclerotic cardiovascular disease; clonal hematopoiesis of indeterminate potential; coronary heart disease; diabetes mellitus; heart failure; hematopoietic stem cell; inflammation; myelopoiesis; somatic mutations; venous thromboembolism
资金
- Fondation Leducq [TNE-18CVD04]
- Stanbury Physician Scientist Pathway of the Massachusetts General Hospital Department of Medicine
- National Heart, Lung, and Blood Institute (NHLBI) T32 postdoctoral training grant [T32HL007604]
- American Heart Association Strategically Focused Research Network in Vascular Disease grant [18SFRN3390085, 18SFRN33960262]
- NHLBI [R01HL141123, K08HL140203]
- Spanish Ministerio de Ciencia, Innovacion y Universidades [RYC-2016-20026]
- Ministerio de Ciencia, Innovacion y Universidades
- Pro CNIC Foundation
- Severo Ochoa Center of Excellence [SEV-2015-0505]
- Hassenfeld Scholar Award from the Massachusetts General Hospital
- Bayer
The incidence of cardiovascular diseases increases with age and is also correlated with increased inflammatory burden. Recently, human genetics provided a new paradigm linking aging, inflammation, and atherosclerotic cardiovascular disease (ASCVD). Next-generation genetic sequencing of whole blood-derived DNA in humans showed that clonal expansion of hematopoietic cells with somatic mutations in leukemogenic genes was associated with age and correlated with increased mortality. This phenomenon, termed clonal hematopoiesis of indeterminate potential (CHIP), was associated with hematologic malignancy as well as ASCVD independently of age and other traditional risk factors. Because the implication of CHIP with ASCVD, genetic loss-of-function studies of Tet2 and Dnmt3a in murine models have supported a mechanistic role for CHIP in promoting vascular disease. Despite the potential contribution of CHIP to myriad cardiovascular and aging-related diseases, the epidemiology and biology surrounding this phenomenon remains incompletely appreciated and understood, especially as applied to clinical practice and prognostication. Here, the authors review this emerging key risk factor, defining its discovery, relationship to cardiovascular diseases, preclinical evidence for causality, and implications for risk prediction and mitigation. (C) 2019 by the American College of Cardiology Foundation.
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