Muscle fat infiltration predicts heart disease risk better than BMI, study finds

New research uncovers how fat hidden in your muscles could be a silent threat to your heart, offering a fresh perspective on cardiovascular risk beyond the scale.

Study: Skeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes. Image Credit: KateStudio / Shutterstock

A recent study published in the European Heart Journal examined the role of skeletal muscle fat infiltration, termed intermuscular adipose tissue (IMAT), in coronary microvascular dysfunction (CMD) and cardiovascular events. By analyzing data from 669 adult patients undergoing evaluation at Brigham and Women’s Hospital between 2007 and 2014, the researchers explored the influence of IMAT on heart health and its potential as a risk marker.

Background

Obesity is a widespread health challenge that is linked to increased risks of cardiovascular diseases (CVD). Although body mass index (BMI) is commonly used to classify obesity and predict related risks, it fails to account for individual variations in fat distribution and metabolic impacts. Furthermore, emerging research has highlighted the importance of ectopic fat depots, including IMAT, which accumulate between muscle fibers and are associated with inflammation, insulin resistance, and metabolic syndromes. The inflammatory properties of IMAT suggest that it may influence the function and energy regulation of neighboring muscle tissues, potentially affecting cardiovascular health.

The study found that nearly 46% of the participants were obese (BMI ≥30 kg/m²), with a median age of 63 years, 70% being female, and 46% identifying as nonwhite, highlighting the demographic diversity of the cohort. Another critical factor in heart disease is CMD, characterized by impaired blood flow despite normal arteries. CMD is strongly linked to inflammation and obesity, but the influence of muscle fat in CMD remains underexplored. Understanding the relationship between IMAT, CMD, and heart disease risk is crucial, as traditional metrics such as BMI may not fully capture cardiovascular risk profiles.

The current study

In the present study, the researchers analyzed the connection between skeletal muscle fat infiltration and cardiovascular health. The study included 669 adult patients undergoing cardiac stress tests using positron emission tomography (PET) and computed tomography (CT) imaging. The participants had no prior history of heart attacks or severe heart conditions and displayed normal heart pump function.

The patients were evaluated for CMD using coronary flow reserve (CFR), calculated as stress/rest myocardial blood flow, which is a key diagnostic measure. Muscle fat distribution, including subcutaneous adipose tissue, skeletal muscle, and IMAT, was assessed from CT images around the 12th thoracic vertebra using semi-automated segmentation software to ensure precision and consistency.

Additionally, the researchers used advanced imaging software to quantify tissue areas and ensure consistency across measurements. IMAT, which is a specific fat depot within skeletal muscles, was of particular interest due to its suspected inflammatory and metabolic roles.

The study excluded patients with known coronary artery disease or advanced health conditions, including end-stage liver, kidney, or lung diseases, to maintain a focus on non-obstructive cardiovascular risks. Furthermore, the imaging data were supplemented with detailed medical histories, medication records, and laboratory results to support a comprehensive analysis. The researchers also adjusted the statistical models for confounding factors such as age, sex, race, BMI, and pre-existing conditions. A significant finding was the interaction between CFR and IMAT, rather than BMI, highlighting IMAT’s role as a more precise risk marker. Associations between muscle fat content, CMD, and adverse cardiovascular outcomes were examined over a median follow-up of nearly six years.

Results

The study reported that skeletal muscle quality and IMAT levels had a significant impact on CMD and cardiovascular outcomes. Lower skeletal muscle mass and higher IMAT were independently linked to reduced CFR, even after adjusting for factors such as BMI and other conventional risk markers.

Moreover, unlike BMI or subcutaneous fat, which showed weaker associations, IMAT emerged as a critical determinant of cardiovascular risk. Higher IMAT levels were also strongly correlated with adverse cardiovascular outcomes, including hospitalizations for heart failure or non-fatal heart attacks, and death. Specifically, each 10 cm² increase in IMAT increased the risk of major adverse cardiovascular events by 53% (95% CI: 1.30–1.80). Conversely, increased skeletal muscle mass and subcutaneous fat appeared protective, even reducing cardiovascular risks.

Importantly, every 1% increase in the fatty muscle fraction (IMAT relative to total muscle mass) was associated with a 2% increased odds of CMD and a 7% higher risk of major adverse cardiovascular events. This relationship was not observed with BMI, which further highlighted IMAT’s potential role as a cardiovascular health marker.

These findings emphasized IMAT’s role as a novel cardiometabolic marker and offered insights into patient risks that BMI or traditional fat measures might miss. This study also highlighted the need for clinical approaches that account for muscle fat distribution, particularly in patients with ischemia and no significant coronary artery blockage.

Conclusions

To summarize, the study indicated that IMAT is a critical factor influencing coronary microvascular dysfunction and adverse cardiovascular outcomes, independent of BMI and conventional risk factors. Identifying patients with both elevated IMAT and CMD could improve risk stratification and treatment strategies.

These findings suggest that traditional obesity measures such as BMI might overlook key risks, reinforcing the need to assess muscle fat composition for more precise cardiovascular risk evaluation. The study introduces a novel at-risk cardiometabolic phenotype, which may pave the way for better-targeted interventions focusing on skeletal muscle health.

These findings also suggested the need to prioritize skeletal muscle health and refine cardiovascular risk assessments beyond traditional metrics, offering new pathways for managing cardiometabolic disease.