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Cited by 386Acute Myeloid Leukemia ResearchAtherosclerosis and Cardiovascular DiseasesHematopoietic Stem Cell Transplantation

Clonal haematopoiesis: connecting ageing and inflammation in cardiovascular disease

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Jaiswal, Siddhartha, Libby, Peter·2020·Nature Reviews Cardiology
DOI 10.1038/s41569-019-0247-5PMC PMC9448847
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Abstract

Ageing and inflammation strongly drive the risk of cardiovascular disease. Work over the past decade has uncovered a common condition characterized by the positive selection of certain somatic mutations in haematopoietic stem cells in ageing humans. This phenomenon, known as clonal haematopoiesis of indeterminate potential (CHIP), occurs most commonly as a result of mutations in the transcriptional regulators DNMT3A, TET2 and ASXL1. CHIP is associated with a variety of adverse outcomes, including haematological cancer and death. Surprisingly, CHIP is also associated with a doubling of the risk of atherosclerotic cardiovascular disease. Studies in mice support the causality of this relationship. Mutations in TET2, which are among the most commonly found mutations in CHIP, lead to increased expression of inflammatory genes in innate immune cells, potentially explaining the link between mutations and increased cardiovascular risk. Therapies targeting the mutant clones or the increased inflammatory mediators might be useful for ameliorating the risk of cardiovascular disease. We propose that the mutations leading to clonal haematopoiesis contribute to the increased inflammation seen in ageing and thereby explain some of the age-related risk of cardiovascular disease.

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  • CHIP carriers have about a 13-fold increased risk of developing myeloid hematological malignancies.

    “CHIP carriers have an about 13-fold increased risk of developing myeloid hematological malignancies and an increased risk of all-cause mortality, largely due to cardiovascular disease and stroke.1, 2, 3, 4”

    From Aging drives <i>Tet2</i> <i>+/−</i> clonal hematopoiesis via IL-1 signaling (2023) · cites this paper as [4]

    The Clinical associations of CHIP section reports an approximately tenfold increased risk of haematological cancer in CHIP carriers and says most cancers that develop are myeloid. It does not report a 13-fold estimate specifically for myeloid malignancies. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • CHIP carriers have increased risk of all-cause mortality, largely due to cardiovascular disease and stroke.

    “CHIP carriers have an about 13-fold increased risk of developing myeloid hematological malignancies and an increased risk of all-cause mortality, largely due to cardiovascular disease and stroke.1, 2, 3, 4”

    From Aging drives <i>Tet2</i> <i>+/−</i> clonal hematopoiesis via IL-1 signaling (2023) · cites this paper as [4]

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Authors
Jaiswal, S., & Libby, P.
Affiliations
  • Stanford Medicine (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Jaiswal, Siddhartha
ORCID
Venue
Nature Reviews Cardiology
Publisher
Springer Science and Business Media LLC
Published
2019-08-12
Volume
17
Issue
3
Pages
137-144
ISSN
  • 1759-5002 (ISSN-L)
  • 1759-5010
DOI
10.1038/s41569-019-0247-5
PMC
PMC9448847
OpenAlex
W2967463001
Cited by
386
References
21
Citations by year
2026: 52 · 2025: 66 · 2024: 56 · 2023: 61 · 2022: 72 · 2021: 41 · 2020: 32 · 2019: 5 · 2012: 1
FWCI
5.98
Type
journal article
Language
en
Update notices
correction (2020-07-02)
Open access
Licence
Locations
  • Nature Reviews Cardiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Burroughs Wellcome Fund
  • Fondation Leducq
  • National Heart, Lung, and Blood Institute (DP2HL157540, R01HL080472)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
clonal hematopoiesis of indeterminate potential, aging, inflammation, atherosclerotic cardiovascular disease, hematopoietic stem cells, somatic mutations, DNMT3A, TET2, ASXL1, innate immune cells
MeSH terms
DNA Methyltransferase 3A, Adult, Age Factors, Aged, Aged, 80 and over, Aging, Animals, Cardiovascular Diseases, DNA (Cytosine-5-)-Methyltransferases, DNA-Binding Proteins, Hematopoiesis, Hematopoietic Stem Cells, Humans, Inflammation, Middle Aged, Mutation, Phenotype, Proto-Oncogene Proteins, Repressor Proteins, Risk Factors, Risk Assessment, Genetic Predisposition to Disease, Dioxygenases

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