Clonal hematopoiesis of indeterminate potential is highly prevalent among elderly patients with a first cardiovascular event and is associated with increased inflammation and more frequent complications

Clonal hematopoiesis of indeterminate potential (CHIP) is defined as an expansion of hematopoietic cells in response to the acquisition of a somatic mutation associated with leukemias, without any sign of hematological malignancy, with a variant allele frequency (VAF) ≥ 2%. It has been described several years ago with a frequency below 20% in the general population and associated with a higher risk of myocardial infarction (MI) and stroke. Experimental data tend to show that the link between CHIP and atherosclerosis would mainly be mediated by a pro-inflammatory phenotype of mutated monocytes infiltrating the atheromatous plaque. To date, few data are available in human pathology. Our study aims to assess the prevalence of CHIP in elderly patients experiencing their first myocardial infarction, and to explore links between CHIP, inflammation and atherosclerosis. We conducted a prospective, single-center study, including patients ≥ 75 years experiencing their first MI. Patients were included 4 (± 2) months after the event. DNA was extracted from total leukocytes, and the presence of CHIP was determined using Next Generation Sequencing on a panel of 56 genes. Inflammation was evaluated through the plasmatic level of high-sensitive CRP (hsCRP) and cytokines (IL-1ß, IL-6, IL-10, IL-18, TNFa). Patients also benefited from a Doppler of the supra-aortic trunks with 3D quantification of the atheromatous volume. The recurrence of cardiovascular events was also evaluated. In total, 149 consecutive patients were included, aged 82.2 ± 4.8 years in mean. Fifty-three percent carried a CHIP, mainly with mutation in DNMT3A (50.6%) and TET2 (32.9%) genes. The CHIP (+) population was older (83.1 vs. 81.1 years in mean, P = 0.011) and less likely to have diabetes (23% vs. 41%, P = 0.021) than the CHIP (−) population. CHIP (+) had a higher hsCRP level than CHIP (−) (2.68 mg/L vs. 1.75 mg/L, P = 0.0019). No difference was found in the levels of IL-1ß, IL-6, IL-10, IL-18 and TNF a, nor in the atheroma burden. Post-MI complications were found in 17.5% of CHIP (+) participants that carried large clones (VAF ≥ 5%) vs. 3.1% of participants who were CHIP (−) (P = 0.013). CHIP is very common in elderly patients with myocardial infarction and appears to be associated with a higher level of inflammation measured by hsCRP and an increased rate of early post-MI complications. On the other hand, the atheroma burden does not seem to be influenced by the presence of a mutation.