Introduction
Overweight or obesity is prevalent in over 71% of US adults and has become one of the most important threats to public health worldwide. Compared to individuals with normal weight, those with obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, experience cardiovascular disease (CVD) events at an earlier age and have a shorter average life span. Excess adiposity accelerates atherosclerosis and promotes adverse changes in cardiac structure and function through deleterious effects on the myocardium as well as the vasculature, and through obesity-related comorbidities, including hypertension, dyslipidaemia, and type 2 diabetes mellitus. Although increasing BMI is associated with increasing risk of morbidity and mortality across populations, CVD risk is not uniform for individuals with similar BMI and can vary substantially across sex and racial/ethnic groups. Nonetheless, BMI thresholds continue to guide current clinical diagnosis of obesity and candidacy for interventions with potential to improve CVD outcomes. Besides BMI, other discriminators of cardiovascular risk are needed in individuals at risk for cardiometabolic disease. Imaging technologies such as computed tomography (CT) can be used to assess body composition and distinguish between fat and lean mass directly in vivo via their respective radiodensities, or attenuation, within anatomical compartments.
Recently, intermuscular adipose tissue (IMAT) has emerged as a distinct adipose depot reflecting skeletal muscle (SM) fat infiltration with unique and evolving biological properties. Whereas fatty ‘marbling’ of meat is commercially valued in livestock, IMAT in humans has been associated with insulin resistance and type 2 diabetes. Intermuscular adipose tissue can be found in most SM groups, and while IMAT increases with BMI, it can vary considerably between individuals. Early reports suggest that IMAT has a proinflammatory secretome with increased expression of interleukin-6 and tumour necrosis factor, which may affect the metabolic function and insulin sensitivity of neighbouring muscle tissue, but the impact of IMAT on CVD events is not well understood.
Coronary microvascular dysfunction (CMD), quantified noninvasively using positron emission tomography (PET) as an impaired global coronary flow reserve (CFR < 2) with normal myocardial perfusion imaging, is independently associated with elevated BMI and future risk of heart failure (HF), myocardial infarction (MI), and death. It is also associated with residual inflammation and myocardial stiffness independently of conventional CVD risk factors in patients with cardiometabolic disease. We previously demonstrated an independent inverted J-shaped relationship between BMI and CFR such that in obese patients, CFR decreased linearly with increasing BMI (adjusted P < .0001). We found that CMD was prevalent in obese patients, worsened with increasing BMI, and was a better discriminator of CVD risk as compared to BMI. Given the limitations of BMI, we sought to investigate the relationship between IMAT, CMD, and cardiovascular outcomes. We hypothesized that measures of both SM quantity and quality are associated with CMD and modify its effect on CVD events independently of obesity.
