Fatty muscle a cardiovascular risk factor independent from BMI
Key takeaways:
- Intermuscular adipose tissue and coronary flow reserve were independent predictors of major adverse CV events.
- The association persisted independently of BMI and other traditional risk factors.
Increased intermuscular fat, not BMI, was independently associated with coronary microvascular function and major adverse CV events, according to new data published in the European Heart Journal.
“Obesity is now one of the biggest global threats to cardiovascular health, yet body mass index — our main metric for defining obesity and thresholds for intervention — remains a controversial and flawed marker of cardiovascular prognosis. This is especially true in women, where high body mass index may reflect more ‘benign’ types of fat,” Viviany R. Taqueti, MD, MPH, director of the cardiac stress laboratory at Brigham and Women's Hospital and faculty at Harvard Medical School, said in a press release. “Intermuscular fat can be found in most muscles in the body, but the amount of fat can vary widely between different people. In our research, we analyze muscle and different types of fat to understand how body composition can influence the small blood vessels or ‘microcirculation’ of the heart, as well as future risk of heart failure, heart attack and death.”
To better understand the relationship between skeletal muscle quality, coronary flow reserve — a marker of coronary microvascular dysfunction — and CV outcomes, Taqueti and colleagues enrolled 669 consecutive patients who underwent cardiac stress testing with PET/CT at Brigham and Women’s Hospital between 2007 and 2014 (median age, 63 years; 70% women; 54% white). All participants had normal perfusion and preserved left ventricular ejection fraction at baseline and were followed up for 6 years for major adverse CV events including death and hospitalization for MI or HF.
Subcutaneous adipose tissue, skeletal muscle and intermuscular adipose tissue areas were obtained from simultaneous PET attenuation correction CT, according to the study methods.
Microvascular dysfunction, fatty muscle and CV risk
Nearly half of patients had obesity — defined as BMI of 30 kg/m2 to 61 kg/m2 — and BMI correlated highly with subcutaneous adipose tissue (r = 0.84) and intermuscular adipose tissue (r = 0.71; P for both < .001) and only moderately with skeletal muscle fat (r = 0.52; P < .001), according to the study.
Lower skeletal muscle (P = .03) and increased intermuscular adipose tissue (P = .04) were both independently associated with decreased coronary flow reserve while BMI and subcutaneous adipose tissue were not.
The researchers reported that lower coronary flow ratio (HR for every 1 U decrease = 1.78; 95% CI, 1.23-2.58; P = .002) and higher intermuscular adipose tissue (HR per 10 cm2 increase = 1.53; 95% CI, 1.3-1.8; P < .0001) were both associated with increased risk for major adverse CV events, whereas increased skeletal muscle (HR per 10 cm2 increase = 0.89; 95% CI, 0.81-0.97; P = .01) and subcutaneous adipose tissue (HR per 10 cm2 increase = 0.94; 95% CI, 0.91-0.98; P = .003) were associated with reduced risk.
The researchers also noted that every 1% increase in fatty muscle fraction — defined as total intermuscular adipose tissue divided by the summation of skeletal muscle and intermuscular adipose tissue — was independently associated with increased likelihood pf coronary microvascular dysfunction (OR = 1.02; 95% CI, 1.01-1.04; P = .04) and risk for major adverse cardiac events (HR = 1.07; 95% CI, 1.04-1.09; P < .001).
Moreover, there was a significant association between coronary flow reserve and intermuscular adipose tissue, not BMI, such that patients with coronary microvascular dysfunction and elevated intermuscular adipose tissue had the highest risk for major adverse CV events (P = .02), according to the study.
“Compared to subcutaneous fat, fat stored in muscles may be contributing to inflammation and altered glucose metabolism leading to insulin resistance and metabolic syndrome. In turn, these chronic insults can cause damage to blood vessels, including those that supply the heart, and the heart muscle itself,” Taqueti said in the release. “Knowing that intermuscular fat raises the risk of heart disease gives us another way to identify people who are at high risk, regardless of their body mass index. These findings could be particularly important for understanding the heart health effects of fat and muscle-modifying incretin-based therapies, including the new class of glucagon-like peptide-1 receptor agonists.”
Additional data needed
In a related editorial, Ranil de Silva, BSc, PhD, MBBS, FRCP, and Kevin Cheng, BM BCh, MRCP, of the Royal Brompton Hospital and National Heart and Lung Institute at Imperial College London, discussed the reported link between coronary microvascular dysfunction, elevated intermuscular adipose tissue and CV risk and how additional data would be required before an intervention trial could be conceived.
“It is well established that coronary microvascular dysfunction can occur across a wide spectrum of cardiovascular diseases. It is increasingly apparent that coronary microvascular dysfunction may be a cardiac manifestation of a wider systemic disorder,” the authors wrote. “As there are many systemic factors in common linking both coronary microvascular dysfunction and intermuscular adipose tissue, including diabetes mellitus, insulin resistance and inflammation, it is conceivable that the increase in intermuscular adipose tissue may potentially be a manifestation of the direct effect of either the above factors on skeletal muscle or microvascular dysfunction extending beyond the heart. This raises the hypothesis that delivering interventions targeted at modifying these shared mechanisms may potentially lead to improved cardiovascular outcome.
“The rationale for conducting a stratified medicine trial of a cardiometabolic modulatory strategy in patients with coronary microvascular dysfunction and elevated intermuscular adipose tissue would require additional confirmation of (i) the causal relationship between elevated intermuscular adipose tissue, coronary microvascular dysfunction and clinical outcomes, and (ii) that these pharmacological strategies achieve positive adaptive responses within skeletal muscle,” they wrote.
References:
- de Silva R, et al. Eur Heart J. 2025;doi:10.1093/eurheartj/ehae909.
- Fatty muscles raise the risk of serious heart disease regardless of overall body weight. https://www.eurekalert.org/news-releases/1070594. Published Jan. 20, 2025. Accessed Jan. 20, 2025.
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