NEW YORK – A team from Harvard Medical School and other centers in the US, France, and Israel has explored potential ties between cardiovascular disease (CVD) and clonal hematopoiesis of indeterminate potential (CHIP), an age-related blood expansion of stem cell populations containing mutations in genes such as DNMT3A or TET2.
The findings appeared in Nature Medicine on Tuesday.
While CHIP has been linked to higher-than-usual CVD risk in individuals from the general population, similar relationships are less clearly defined in clinical cohorts of individuals who have already been diagnosed with heart disease or received related treatments.
The researchers conducted exome sequencing on 63,700 individuals between the ages of 59 and 72 years old who were enrolled in five randomized clinical trials conducted by the Brigham and Women's Hospital "Thrombolysis in Myocardial Infarction Clinical Trials" (TIMI) Study Group and searched this data for potential associations or predictive ties between CHIP and cardiovascular disease, CVD-related death, or treatment responses.
"Clinical trial data have the benefit of carefully defined populations enriched for [cardiovascular] events, rigorous follow-up, formally adjudicated events, and randomized treatment assignments," corresponding and co-first author Nicholas Marston, a researcher with the Harvard Medical School Brigham and Women's Hospital TIMI Study Group, and his colleagues explained.
More than half of the individuals profiled had been diagnosed with diabetes and nearly three-quarters had atherosclerotic diseases such as peripheral artery disease, a history of myocardial infarction, or a prior stroke when the study began. Consistent with past studies, the team saw increasing rates of CHIP in older individuals, with CHIP turning up in 8.2 percent of the participants overall.
Over two and a half years of follow-up time, on average, the researchers saw cardiovascular events — ranging from ischemic stroke, coronary revascularization, or myocardial infarction to cardiovascular disease-related deaths — in 7,453 individuals.
Although they noted a small uptick in these cardiovascular events in individuals with CHIP, the potential relationship between the conditions was modest and heterogeneous. When it came to myocardial infarction, for example, the investigators uncovered a 30 percent rise in an initial event in CHIP-positive individuals, despite a comparable risk of recurrent myocardial infarction in those with or without CHIP.
"CHIP was associated with incidents but not recurrent coronary events, suggesting its use for prognostic enrichment of clinical trials may be more applicable in primary prevention populations," the authors reported, though they noted that this pattern may reflect the use of high-dose statins or other prior treatments in clinical trial participants.
Likewise, the investigators did not see variation when it came to treatment response when they compared outcomes for individuals with or without CHIP.
Still, the lack of a clear association between CHIP and response to the various treatments tested in the trials remains clinically informative, the authors explained, suggesting that "patients with CHIP will benefit similarly from guideline-based clinical care with respect to lipid-lowering therapy, anticoagulant, and antiplatelet therapy — four cornerstones of our clinical armamentarium."