Quantity of Body Fat, Rather Than Location, May Be Key for Cardiovascular Diseases

Increased obesity worldwide has become a leading cause of cardiovascular diseases. A new study by UC San Francisco and the Broad Institute of MIT and Harvard researchers found the quantity of fat tissue rather than its location – either in the abdomen or around the heart – was a greater determinant of cardiovascular disease risk. 

The multi-center, large cohort study looked at the cardiovascular effect of epicardial and pericardial adipose tissue (EPAT) using AI modeling and genetic determinants and found that the quantity of EPAT was predictive of type 2 diabetes, heart failure and coronary artery disease.

When researchers included prior measurements of abdominal fat tissue (visceral adipose tissue) to the EPAT measurements, they found that EPAT did not present unique risk factors for those diseases, but instead showed that quantity of the fat tissue in patients is a more important factor than where the fat tissue is found.

The study was published March 13, 2024, in JAMA Cardiology. 

The researchers used a deep learning AI model to quantify EPAT based on four-chamber magnetic resonance heart images of 44,725 UK Biobank (UKB) participants. They used the AI-based EPAT fat measurements to see the associations with diseases that were diagnosed after the MRI’s were completed.

They also performed a genome-wide association study to evaluate the hereditary genetic determinants (genotype) of EPAT in UKB participants as well as from 453,733 study participants in the independent Finnish biobank study (FinnGen).

Best to reduce all fat to improve cardiovascular health

The research team determined that a higher EPAT polygenic score (PGS) – the disease risk due to a person’s hereditary genetic make up – was also associated with type 2 diabetes, heart failure, coronary artery disease, stroke and atrial fibrillation. However, EPAT was more elevated in participants with prevalent heart failure and type 2 diabetes than in coronary artery disease or atrial fibrillation. 

“Coupled with advances in deep learning-based annotation, the use of this large dataset enabled the assessment of visceral adipose deposits in the chest and abdomen, as well as genetic data and longitudinal disease outcomes, all in the same individuals,” said senior author James Pirruccello, MD, a cardiologist and UCSF assistant professor of Medicine. “The genetic evidence, in particular, points to a largely shared basis for visceral adipose tissue regardless of location.”

Additionally, genotyping of participants allowed for the simultaneous evaluation of the hereditary determinants of EPAT in a sample many times larger than previous cohorts. The researchers found seven genetic locations for epicardial and pericardial adipose tissue development including genes influencing adipocyte (fat cell) structure, brown-like adipose tissue differentiation (found in the epicardium) and abdominal adiposity.

“For now, our results suggest that efforts to reduce all visceral adiposity are likely to be beneficial for cardiovascular disease risk without requiring specialized testing to assess thoracic adiposity,” said Pirruccello. 

Authors: The first author is Joel T Rämö, MD, PhD, Broad Institute of MIT and Harvard. For additional authors, please see the study.

Funding: Dr. Rämö was supported by a Fellowship from the Sigrid Jusélius Foundation. Dr. Pirruccello was supported by a Sarnoff Scholar Award and National Institutes of Health (NIH) grant K08HL159346. For additional funding, please the study.
 

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