Unhealthy Diet Linked to CHIP Mutation and CVD

Fran Lowry

June 25, 2021

An unhealthy diet is associated with a higher prevalence of clonal hematopoiesis of indeterminate potential (CHIP), a genetic variation that researchers say is a novel risk factor of "emerging importance," and with higher rates of adverse cardiovascular events and death, independent of CHIP status, a new study suggests.

In an observational study of more than 44,000 adults, an unhealthy diet that was low in fruits and vegetables and high in red meat was associated with a 25% increased likelihood of the presence of CHIP, which is a known risk factor for both hematologic cancer and cardiovascular disease (CVD). This prevalence decreased with improved diet quality.

Participants who reported having healthier diets had the fewest cardiovascular events, although this finding was not statistically significant.

The study, which was led by Romit Bhattacharya, MD, Massachusetts General Hospital, Boston, was published online June 9 in JAMA Cardiology.

CHIP is a somatic mutation found in hematopoietic stem cells of the blood or bone marrow. Its prevalence, which rises with age, is about 10% in those older than 70 years. People with CHIP are known to be at increased risk for blood cancers such as leukemia, as well as CVD.

In this analysis, Bhattacharya and his team sought to see if there was an association between diet quality and the prevalence of CHIP.

Their retrospective cohort study used data on 44,111 participants in the UK Biobank, aged 40 to 70 years, who had results available from whole-exome sequencing of blood DNA and were free of coronary artery disease or hematologic cancer at study entry.

The participants were recruited from 2006 to 2010 and followed prospectively through May 2020.

At the baseline visit, participants used a touch screen to provide detailed information about their medical history, medications, smoking history, and dietary habits, among other lifestyle factors.

Responses on food frequency questionnaires were used to assess diet quality.

Diets were categorized as unhealthy if the intake of healthy foods (i.e., fruits and vegetables) was lower than the median of all survey responses, and if the intake of unhealthy foods (i.e., red meat, processed food, and added salt) was higher than the median.

Healthy diets were defined as the reverse of unhealthy diets.

The remaining individuals were categorized as having a diet of intermediate quality.

Most of the cohort (87.4%) had an intermediate diet, 7.5% had a healthy diet, and 5.1% had an unhealthy diet.

Overall, CHIP was identified in 5.7% of the cohort, and its prevalence decreased as diet quality improved.

The prevalence of CHIP was 7.1% among participants with an unhealthy diet, 5.7% among those with an intermediate diet, and 5.1% among those with a healthy diet (= .003 for trend).

Individuals with CHIP and healthy diets had the fewest incident cardiovascular events, although this finding was not statistically significant.

Importantly, no incident cancers occurred among the individuals with CHIP.

Novel CVD Risk Factor

Preventive cardiologists have begun to take interest in CHIP because it is becoming a newly appreciated risk factor for CVD.

Pradeep Natarajan

"As our lab and others identified a few years ago, CHIP is a novel CV risk factor that is emerging in importance," senior author, Pradeep Natarajan, MD, director of preventive cardiology at Massachusetts General Hospital, told theheart.org | Medscape Cardiology.

"Despite knowledge of modifiable risk factors that have been well recognized for the past 5 decades, cardiovascular disease remains the leading cause of death in the world. That motivates our interest in identifying novel factors that may be influencing this risk," Natarajan said. "If CHIP is being caused by a bad diet, then changing the diet to a more healthy one could potentially be helpful."

Interesting Observational Study

Hina Chaudhry

"This observational analysis suggests that dietary intervention may provide a low-risk therapeutic intervention for individuals with CHIP, but isn't this common sense?" said Hina Chaudhry, MD, director of cardiovascular regenerative medicine, Mount Sinai, New York City.

"A bad diet induces drastic alterations in your epigenome, so it is inducing atherosclerosis through many mechanisms other than CHIP. All that we know right now is that CHIP is associated, it is not causative, but a bad diet is going to set you up for everything," Chaudhry said.

Sangeetha Vadakke-Madathil

"The heritability of CHIP is very low, so it's important to look at what other factors promote CHIP. Hence, this study can be a valuable tool," added Sangeetha Vadakke-Madathil, PhD, an instructor in medicine at Mount Sinai who works with Chaudhry in her research lab.

But there are issues with the paper, Vadakke-Madathil said.

"Surveys can be error prone," she explained. "Also, CHIP-associated genes are unchanged, or altered, across dietary classes. And finally, although healthier diets among individuals with CHIP had the fewest incident CV events, the finding was not statistically significant, as they state in their discussion."

The study was supported by grants from the National Institutes of Health; National Heart, Lung, and Blood Institute; and Massachusetts General Hospital. Bhattacharya reported receiving personal fees from Casana outside the submitted work. Natarajan reported financial relationships with Amgen, Apple, AstraZeneca, Blackstone Life Sciences, Boston Scientific, Genentech, and Novartis. Chaudhry and Vadakke-Madathil report no relevant financial relationships.

JAMA Cardiol. Published online June 9, 2021. Abstract

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