Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease

Area of Science:

• Cardiovascular Medicine
• Hematology
• Genetics

Background:

• Clonal hematopoiesis (CH) is a known risk factor for atherosclerotic cardiovascular disease.
• The impact of smaller CH clones and inflammatory markers on cardiovascular events remains unclear.

Purpose of the Study:

• To investigate the association between CH and major adverse cardiovascular events (MACE) in stable coronary artery disease (CAD) patients.
• To determine if clone size predicts MACE and to identify associated inflammatory biomarkers.

Main Methods:

• Ultrasensitive single-molecule molecular inversion probe sequencing was used to detect CH.
• Association between CH and MACE was assessed over a four-year follow-up in patients with stable CAD.

Main Results:

• CH was linked to an increased rate of MACE over four years.
• Clone size, with a cut-off of 1.07% variant allele frequency (VAF), predicted MACE.
• Higher levels of circulating tissue factor, matrilysin, and proteinase-activated receptor-1 were observed in mutation carriers.

Conclusions:

• CH driver mutations, even at 1.07% VAF, represent a residual cardiovascular risk factor in stable CAD.
• Identified biomarkers suggest potential therapeutic targets for managing cardiovascular risk in these patients.