ABSTRACT
Age is the most important risk factor for cardiovascular disease and appears to be
more than a marker of cumulative exposure to other risk factors such as dyslipidemia
and hypertension. With aging, genetic mutations occur that are not present in our
germline DNA, observed as somatic mosaicism. Hematopoietic stem cells have an increased
chance of developing mosaicism because they are highly proliferative, and mutations
with survival benefits can establish clonal populations. Age-related clonal hematopoiesis
resulting from somatic mutations was first described ∼25 years ago. The subset of
clonal hematopoiesis in which a driver mutation with variant allele frequency of at
least 2% occurs in a gene implicated in hematologic malignancies but in the absence
of known hematologic malignancy or other clonal disorder is termed clonal hematopoiesis
of indeterminate potential (CHIP). Large-scale exome-sequencing projects have recently
enabled the study of CHIP frequency, gene-specific analyses, and longitudinal clinical
consequences of CHIP, including an observed increased risk for cardiovascular disease.
Animal models provide insight into the mechanisms by which CHIP increases cardiovascular
disease risk, and combined animal, clinical, and epidemiological data suggest therapeutic
implications for CHIP in cardiovascular disease prevention.
Abbreviations:
AIM2 (absent in melanoma–2), ASCVD (atherosclerotic cardiovascular disease), BM (bone marrow), CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study), CHD (coronary heart disease), CHIP (clonal hematopoiesis of indeterminate potential), CI (confidence interval), FUSION (Finland–United States Investigation of NIDDM Genetics), HR (hazard ratio), HSC (hematopoietic stem cell), IL (interleukin), LDL (low-density lipoprotein), MGBB (Mass General Brigham Biobank), NLRP3 (nucleotide-binding oligomerization domain–like receptor family pyrin domain containing–3), OR (odds ratio), PAD (peripheral artery disease), UKBB (UK Biobank), VAF (variant allele frequency. Non-peer-reviewed references are indicated as #P, preprint and #A, abstract)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: September 02, 2022
Accepted:
August 27,
2022
Received in revised form:
August 25,
2022
Received:
August 3,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
