The presence of clonal hematopoiesis (CH) of indeterminate potential (CHIP) among older patients — many of whom had coronary artery disease (CAD) — was associated with higher high-sensitivity C-reactive protein (hs-CRP) levels, according to a study published in Blood Advances.

“CH prevalence increases significantly in patients aged >60 years old and confers an increased risk of progression to hematological cancers and cardiovascular diseases,” the authors wrote. CH is caused by acquired mutations, but the underlying etiology of clonal initiation and expansion is unknown.

The authors wrote that, “The association between CHIP and both cardiovascular and chronic pulmonary disease raised the possibility that age-associated chronic inflammation may be a key commend denominator between these medical conditions.” The purpose of this study was to determine if CHIP is associated with inflammation.

The study included 1887 subjects 70 years and older, of whom, 1359 had CAD as defined as a prior history of myocardial infarction, percutaneous coronary intervention (PCI), or coronary artery bypass graft surgery. The remaining subjects did not have a history of CAD. All subjects were from the Montreal Heart Institute biobank, which is a prospective cohort used for clinical and genetic research.


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CHIP analysis was performed using next-generation sequencing using a custom panel validated for coverage, specificity, and sensitivity. The panel included 11 genes that were previously associated with CHIP. Any frameshift, nonsense, in-frame deletions or insertions, splicing, or consequential missense alterations were considered significant.

Among all patients, 22.6% had CHIP and 17.5% of these cases were due to a single mutation. The presence of CHIP was similar between the CAD and non-CAD groups (21.5% vs 25.3%; P =.075). The most commonly mutated genes among all patients were DNMT3A, TET2, and ASXL1. TET2 mutations were significantly more common among patients without baseline CAD at 9% compared with 4.9% among patients with a history of CAD (P <.001). The prevalence of other mutated genes was similar between the groups.

Subjects with CHIP were significantly more likely to also have higher levels of hs-CRP with a median of 1.60 mg/L compared with 1.41 mg/L among subjects without CHIP (P =.009). CHIP was also significantly associated with older age (P =.002), lack of dyslipidemia (P =.041), and fewer PCIs (P =.006).

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Subjects with CHIP with a DNMT3A mutation were significantly more likely to have higher hs-CRP levels compared with subjects with CHIP without a DNMT3A mutation (P =.04). There was no association between hs-CRP level and other mutated genes.

In the CAD group, CHIP was associated with older age, fewer PCIs, more congestive heart failure, and higher hs-CRP compared with patients without CHIP. In contrast, hs-CRP levels were similar between CHIP carriers and non-carriers in the non-CAD group.

According to the authors, these data suggest that inflammation is involved in the etiology of CHIP. The authors suggested that “clinical trials should test whether anti-inflammatory therapy can reduce CHIP progression and related diseases.”

Reference

Busque L, Sun M, Buscarlet M, et al. High-sensitivity C-reactive protein is associated with clonal hematopoiesis of indeterminate potential. Blood Adv. 2020;4(11):2430-2438.