Increased intermuscular adipose tissue may be independently associated with coronary microvascular dysfunction and adverse cardiovascular outcomes, irrespective of body mass index or conventional risk factors, according to a new study.
In the study, published in the European Heart Journal, researchers from Harvard-affiliated institutions conducted a prospective study on 669 consecutive patients who underwent cardiac stress positron emission tomography (PET) imaging. The study defined coronary microvascular dysfunction (CMD) as a coronary flow reserve (CFR) of less than 2 and tracked participants for a median of 5.8 years. The findings showed that every 1% increase in fatty muscle fraction conferred a 2% increased risk of CMD (P = .04) and a 7% higher risk of major adverse cardiovascular events (MACE; P < .001).
“The presence of both CMD and intermuscular adipose tissue (IMAT) identified a novel at-risk cardiometabolic phenotype prevalent in patients with [ischemia and no obstructive coronary artery disease] (INOCA),” the study authors reported.
The study population had a median age of 63 years and was predominantly female (70%). Nearly half (46%) of the participants were classified as having obesity, with a body mass index (BMI) ranging from 30 to 61 kg/m². The researchers quantified IMAT, skeletal muscle (SM), and subcutaneous adipose tissue (SAT) using semi-automated segmentation of computed tomography (CT) images at the T12 vertebral level.
Key findings revealed that increased IMAT and decreased SM were independently associated with lower CFR (adjusted P = .03 and P = .04, respectively). Higher IMAT was also linked to increased MACE risk (hazard ratio [HR] = 1.53 per +10 cm², P < .0001). Conversely, higher SM and SAT demonstrated protective effects (HR = 0.89 per +10 cm² and HR = 0.94 per +10 cm²; P = .01 and P = .003, respectively). A significant interaction was observed between CFR and IMAT, with patients exhibiting both CMD and high IMAT facing the highest MACE risk (interaction P = .02). The adjusted annualized rate of adverse events among these patients was 5.1%.
These results have particular relevance among patients with INOCA, a condition more prevalent in women, where traditional risk assessments based on BMI may fail to capture obesity-related cardiovascular risk adequately.
The study’s observational, single-center design limited its generalizability. While multivariable adjustments were made, the researchers noted that residual confounding could not be entirely excluded. Additionally, body composition metrics were derived from thoracic imaging, which may differ from abdominal measurements commonly used in other studies.
The study authors concluded that "opportunistic CT used in this manner may provide personalized prognostic information without added cost or radiation exposure and is poised to grow with rapid developments in artificial intelligence and machine learning." The researchers also highlighted the need for further investigation into therapeutic strategies, including supervised exercise and nutritional, medical, or surgical weight-loss interventions, targeting improvements in skeletal muscle quality and CMD outcomes.
Full disclosures can be found in the study.
