medwireNews: People with chest pain or dyspnea who have high levels of intermuscular adipose tissue (IMAT) within skeletal muscle have a significantly increased risk for major cardiovascular events (MACE), irrespective of their BMI, suggests a study in the European Heart Journal.
Investigators Viviany Taqueti (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and colleagues report a significant 53% higher risk for MACE, a composite of death, hospitalization for nonfatal myocardial infarction, or heart failure, with every 10 cm2 increase in IMAT, assessed with PET/CT at the 12th thoracic vertebrae level.
The team also found a significantly increased risk for MACE among individuals with low coronary flow reserve (CFR), a marker of coronary microvascular dysfunction (CMD), rising by 78% with every 1-unit reduction in CFR. The elevated risks associated with both IMAT and CFR remained even after adjustment for baseline cardiovascular risk factors, BMI, and subcutaneous, epicardial, or hepatic fat depots.
A total of 669 adults referred for cardiac stress testing with positron emission tomography (PET)/computed tomography (CT) to investigate chest pain and/or dyspnea participated in the study.
Their median age was 62.6 years, 69.8% were women, and 46.2% were nonWhite. They had ischemia but not obstructive coronary artery disease, with a summed stress score below 2 points and a left ventricular ejection fraction of at least 40%. Median BMI was 29.2 kg/m2, and 46% of the cohort were categorized as obese, with a BMI of 30–61 kg/m2. BMI significantly correlated with both IMAT and subcutaneous adipose tissue.
Over a median of 5.8 years, 8.1% of the participants died, 4.9% were hospitalized for nonfatal myocardial infarction, and 5.1% had heart failure. Taqueti et al say the presence of both increased IMAT and CMD conferred the highest risk for adverse cardiovascular events independently of BMI.
“There was a significant interaction between CFR and IMAT, not BMI, such that patients with both CMD and fatty muscle demonstrated highest MACE risk,” they comment.
By contrast, high levels of skeletal muscle and subcutaneous adipose tissue protected against the risk for MACE, reducing the risk by a significant 11% and 6% with every 10 cm2 increase in each.
After calculating the fatty muscle fraction (ie, the ratio of IMAT to total skeletal muscle plus IMAT), the investigators found that “[e]very 1% increase in thoracic fatty muscle fraction conferred an independent 2% increased odds of CMD and a 7% increased risk of [MACE].”
They say that the “data support that thoracic [skeletal muscle] quantity and quality are tied to coronary microvascular function and together identify a novel at-risk cardiometabolic phenotype,” and suggest that IMAT may “promote an adverse muscle phenotype associated with metabolic derangements, including impaired bioenergetics, mitochondrial dysfunction, and increased catabolism with loss of lean muscle mass.”
Commenting on the findings in a related editorial, Ranil de Silva and Kevin Cheng (both from the National Heart and Lung Institute, Imperial college, London, UK) say that they “reinforce the importance of low CFR as a marker of increased clinical risk and now suggest IMAT as an additional risk stratifier in this elevated-risk group.” They add that “the clinical utility of these results will require verification in an independent cohort.”
De Silva and Cheng note that study was limited by its observational single-center design, the possibility that muscle composition at the 12th thoracic vertebrae may differ from that obtained at the lumbar spine, and the lack of abdominal visceral adipose tissue quantification.
They also point out that details on circulating inflammatory biomarkers, insulin resistance, endothelial function, diet, skeletal muscle physiology, or exercise performance were not available.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of the Springer Nature Group
Eur Heart J 2024; doi:10.1093/eurheartj/ehae827
Eur Heart J 2025; doi:10.1093/eurheartj/ehae909