Clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular disease

Clonal hematopoiesis of indeterminate potential (CHIP) is due to somatic mutations which cause expansion of hematopoietic stem cells. This is in the absence of overt hematologic malignancy. CHIP is more common in the elderly and increases cardiovascular risk independent of traditional risk factors. There is also an increased risk for development of hematological malignancies. There is an association of a pro-inflammatory state with CHIP which has been linked to coronary artery disease, myocardial infarction, venous thromboembolism and prognosis in those with aortic stenosis and heart failure [1]. CHIP may have implications for risk prediction and mitigation [2].

338 patients in the CANTOS trial of canakinumab had evidence for clonal hematopoiesis [3]. As expected, patients with CHIP were older, with a mean age of 66.3 years compared to 61.5 years in those without CHIP. Placebo treated patients with CHIP had a nonsignificant increase in the rate of major adverse cardiovascular events compared to those without CHIP. Patients on canakinumab with CHIP due to somatic variants in TET2 gene showed a reduced risk of MACE. Thus there is an indication of the role of inflammation in these patients. CANTOS trial had selected patients with elevated C-reactive protein for randomization.

References

1. Marnell CS, Bick A, Natarajan P. Clonal hematopoiesis of indeterminate potential (CHIP): Linking somatic mutations, hematopoiesis, chronic inflammation and cardiovascular disease. J Mol Cell Cardiol. 2021 Dec;161:98-105. doi: 10.1016/j.yjmcc.2021.07.004. Epub 2021 Jul 21. PMID: 34298011; PMCID: PMC8629838.
2. Khetarpal SA, Qamar A, Bick AG, Fuster JJ, Kathiresan S, Jaiswal S, Natarajan P. Clonal Hematopoiesis of Indeterminate Potential Reshapes Age-Related CVD: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Jul 30;74(4):578-586. doi: 10.1016/j.jacc.2019.05.045. PMID: 31345433; PMCID: PMC6662618.
3. Svensson EC, Madar A, Campbell CD, He Y, Sultan M, Healey ML, Xu H, D’Aco K, Fernandez A, Wache-Mainier C, Libby P, Ridker PM, Beste MT, Basson CT. TET2-Driven Clonal Hematopoiesis and Response to Canakinumab: An Exploratory Analysis of the CANTOS Randomized Clinical Trial. JAMA Cardiol. 2022 May 1;7(5):521-528. doi: 10.1001/jamacardio.2022.0386. PMID: 35385050; PMCID: PMC8988022.