CHIP predicts adverse outcomes in atherosclerotic CVD

Clonal haematopoiesis of indeterminate potential (CHIP) appears to independently contribute to adverse outcomes in individuals with established atherosclerotic cardiovascular disease (ASCVD), reveals a recent study, noting the high risks in TET2 and SF3B1/SRSF2/U2AF1 CHIP.

The authors analysed individuals aged 40‒70 years from the UK Biobank with established ASCVD and available whole-exome sequences. They compared the associations of any CHIP (variant allele fraction ≥2 percent), large CHIP clone (variant allele fraction ≥10 percent), and the most commonly mutated driver genes (DNMT3A, TET2, ASXL1, JAK2, PPM1D/TP53 [DNA damage repair genes], and SF3B1/SRSF2/U2AF1 [spliceosome genes]). A composite of ASCVD events and all-cause mortality was the primary outcome.

In total, 13,129 individuals (median age 63 years) were included in the analysis. Of these, 665 (5.1 percent) had CHIP. Any CHIP and large CHIP at baseline significantly correlated with an increased risk of the primary outcome (any CHIP: adjusted hazard ratio [HR], 1.23, 95 percent confidence interval [CI], 1.10‒1.38; p<0.001; large CHIP: adjusted HR, 1.34, 95 percent CI, 1.17‒1.53; p<0.001).

Notably, TET2 and spliceosome CHIP, especially large clones, showed the most robust association with adverse outcomes (large TET2 CHIP; HR, 1.89, 95 percent CI, 1.40‒2.55; p<0.001; large spliceosome CHIP: HR, 3.02, 95 percent CI, 1.95‒4.70; p<0.001).

“CHIP, the age-related clonal expansion of blood stem cells with leukaemia-associated mutations, is a novel cardiovascular risk factor,” the authors said.