Clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular diseases—an updated systematic review

Abstract

Background Cardiovascular diseases (CVDs) are the leading cause of mortality in India. Residual risk exists in patients receiving optimal guideline-directed medical therapy. Possession of certain somatic mutations, at a variant allele frequency of ≥ 2% in peripheral blood, driving clonal expansion in the absence of cytopenias and dysplastic hematopoiesis is defined as clonal hematopoiesis of indeterminate potential (CHIP). Recently, it was found that carriers of CHIP had a higher risk to have coronary artery disease (CAD) and early-onset myocardial infarction. Association of CHIP with heart failure and valvular heart diseases is increasingly being considered. The common link that connects CHIP mutations and CVDs is inflammation leading to increased expression of cytokines and chemokines. We intended to do a systematic review about the association of CHIP mutations and CVD along with identifying specific CHIP mutations involved in increasing the risk of having CVDs. The main body of the abstract We performed an extensive literature search in PubMed and Google Scholar databases. Out of 302 articles, we narrowed it down to 10 studies based on our pre-specified criteria. The methodology adopted for the identification of CHIP mutations in the selected studies included – whole-exome sequencing (n = 3), whole-genome analysis (n = 1), transcriptome profiling analysis (n = 1), whole-genome analysis (n = 1), and single-cell RNA-sequencing (n = 1). We found that the available literature suggested an association between CHIP and CVD. The most commonly described CHIP mutations in patients with CVD are DNMT3A, TET2, ASXL1, TP53, JAK2, and SF3B. We further analyzed the commonly mutated CHIP genes using bioinformatics tools. Protein function and interaction analysis were performed using the g: Profiler and GeneMANIA online tools. The results revealed significant bio grid interactions for molecular functions, biological processes, and biological pathways. Interaction analysis showed significant physical and co-expression interactions. Short conclusion We conclude that there exists a significant association between CHIP mutations and CVD with DNMT3A, TET2, ASXL1, TP53, JAK2, and SF3B as the commonly implicated genes. The recognition of the link between CHIP and cardiovascular events will expand our understanding of residual risk and will open up new avenues of investigation and therapeutic modalities in the management of patients with CVD.

Clinical significance of clonal hematopoiesis in the setting of autologous stem cell transplantation for lymphoma

“…7,8 CH has been associated with numerous adverse health outcomes, including an increased incidence of hematological malignancies, 3,4,9 adverse cancer outcomes, 10,11 risk of infections, 12,13 osteoporosis, 14 and cardiovascular disease. [15][16][17] Together, these associations appear to largely explain the inferior survival that is seen in individuals with CH. 3,4 The relationship between CH and subsequent hematological malignancies is complex with tumor cell autonomous and non-cell autonomous effects.…”

“…The concept of CH has been extended to mosaic chromosomal alterations that, similar to mutation‐defined CH, increases in frequency with advancing age 7,8 . CH has been associated with numerous adverse health outcomes, including an increased incidence of hematological malignancies, 3,4,9 adverse cancer outcomes, 10,11 risk of infections, 12,13 osteoporosis, 14 and cardiovascular disease 15–17 . Together, these associations appear to largely explain the inferior survival that is seen in individuals with CH 3,4 …”

High residual cardiovascular risk after lipid-lowering: prime time for Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive medicine

“…Clonal hematopoiesis of indeterminate potential (CHIP), a collection of somatic mutations, is an age-associated risk factor for MI, stroke, heart failure events, and survival following percutaneous aortic valve intervention ( 129 , 130 ). It is suggested that CHIP activates the inflammasome pathway and contributes to thrombosis, leading to CVD.…”

A Synopsis Clonal Hematopoiesis of Indeterminate Potential in Hematology

“…Inflammatory macrophages are instrumental to the pathogenesis of atherosclerosis. Therefore, the resulting positive feedback loop between CHIP and chronic inflammation increases the risk of development of atherosclerosis and chronic heart failure [ 18 , 25 ].…”