An Unhealthy Diet Feeds Into Clonal Hematopoiesis

Diet may play a role in the development of an age-linked condition associated with atherosclerotic cardiovascular disease (CVD), a retrospective cohort study found.

In the U.K. Biobank, worse diet quality was associated with greater prevalence of clonal hematopoiesis of indeterminate potential (CHIP) — 7.1% with unhealthy diets versus 5.7% with intermediate diets versus 5.1% with healthy diets (P=0.003 for trend), according to Pradeep Natarajan, MD, MMSc, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues.

Among people with CHIP, those with unhealthy diets suffered more CVD events over 10 years than peers with intermediate diets (HR 1.52, 95% CI 1.04-2.22), who in turn shared similar CVD risk to those with healthy diets (HR 0.99, 95% CI 0.62-1.58), the group reported online in JAMA Cardiology.

“CHIP is a newly recognized risk factor for CVD that is higher among individuals with unhealthy diets. Among individuals with CHIP, diet quality remains an independent risk factor that can be used to stratify CVD risk,” Natarajan and colleagues concluded.

Characterized by clonal expansion in leukemogenic genes in hematopoietic stem cells without any overt diagnosis of cancer, CHIP can be detected by next-generation sequencing of blood DNA in asymptomatic individuals. The age-associated phenomenon is common, having been reported in up to 10% of people older than 70.

“While CHIP is a substantial risk factor for the development of hematologic cancer, it is associated with a larger absolute risk increase for [coronary artery disease],” the authors noted.

The condition has also been tied to an excessive inflammatory response in COVID-19 among elderly people and patients with CVD.

Given the low established risk of inheriting CHIP, the group hypothesized that lifestyle and diet may play a role in its development.

To test this, Natarajan and colleagues linked whole-exome sequencing data, lifestyle survey reports, and health records of participants in the ongoing population-based U.K. Biobank study.

The 44,111 people included in the present analysis (mean age 56.3 years, 55.6% women) were those who had sufficient genotyping data and were free of coronary artery disease or hematologic cancer when recruited in 2006 to 2010.

Study participants had their diets classified as unhealthy (5.1%), intermediate (87.4%), or healthy (7.5%).

An unhealthy diet was said to be one in which intake of fruits and vegetables was lower than the median of all survey responses, and intake of red meat, processed food, and added salt was higher than the median. Healthy diets were characterized as being just the opposite.

The observational nature of the study left room for unmeasured confounding and precluded any causal findings, Natarajan’s team cautioned.

“[T]he results of the current study support the notion that dietary pattern may mitigate the risk of excess CVD among individuals with CHIP,” the group maintained. “Although there are several hypotheses regarding anti-inflammatory therapies, approved dedicated therapies for the reduction of CHIP-associated CVD are currently absent.”