Summary
A medRxiv preprint reports different somatic mutation patterns in blood and arterial samples from patients undergoing coronary bypass surgery. Only four identical variants were found in both tissues among 221 matched pairs.
A medRxiv preprint reports different patterns of acquired mutations in blood and arterial tissue from patients undergoing coronary artery bypass graft surgery. In 221 matched pairs, researchers found only four identical variants in both compartments, suggesting that blood testing may not capture the full range of mutations detected in arterial samples.
The study used deep whole-exome sequencing of 302 blood granulocyte samples and 263 arterial tissue samples. Average sequencing depth was 130.5× for blood and 120.8× for arterial tissue. The primary analyses focused on variants with a variant allele fraction (VAF)—the proportion of sequence reads carrying a variant—of 10–25%.
Different mutation patterns in blood and arteries
Clonal hematopoiesis of indeterminate potential, or CHIP, describes the expansion of blood-cell populations descended from a cell that acquired a mutation. The researchers detected CHIP in 24 of 302 blood samples (7.9%), most often involving the genes DNMT3A, TET2 and ASXL1.
The profile in arterial samples differed. Among mutations in genes associated with CHIP, the arterial findings were led by CALR, SETDB1 and PDSS2. Across the 221 matched pairs, the four identical variants found in both compartments involved CHEK2, DNMT3A, GNB1 and SRSF1.
Mutation carrier status increased with age in both blood (β = 0.07, p = 0.02) and arterial tissue (β = 0.06, p = 0.04). The relationships with coronary disease complexity differed by compartment. Blood CHIP was associated with a lower SYNTAX score, a measure of the anatomical complexity of coronary artery disease (β = −1.05, p = 2.66 × 10⁻³); the association was partly driven by DNMT3A carriers (β = −1.06, p = 0.04). In contrast, arterial CALR mutations were associated with a higher SYNTAX score (β = 1.14, p = 0.03). These regression results describe associations in the study cohort, not causal effects of the mutations.
Genome-wide analysis also found compartment-specific signals, with bile acid metabolism enriched among mutations detected only in arterial tissue (adjusted p = 0.038).
Interpreting the findings
The results point to distinct mutation patterns in blood and arterial samples from people with coronary artery disease. That distinction matters because studies of CHIP and cardiovascular disease have largely relied on blood: the findings suggest that blood alone may not represent all somatic mutations present in arterial tissue.
The study examined samples from patients undergoing bypass surgery, so its results may not apply in the same way to other populations with coronary artery disease. It is also a preprint. Because the analysis used tissue samples rather than cell-resolved or spatial methods, the origins of the arterial mutations and their roles in disease remain to be established. The authors identify cell-resolved and spatial studies as next steps.