Intra-thoracic fat, cardiometabolic risk factors, and subclinical cardiovascular disease in healthy, recently menopausal women screened for the Kronos Early Estrogen Prevention Study (KEEPS)

Objective: To examine the correlations between intra-hepatic and intra-thoracic (total, epicardial, and pericardial) fat deposition with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis burden in healthy, recently postmenopausal women. Methods: Women screened for the Kronos Early Estrogen Prevention Study (mean age 52.9 years) who underwent electron beam or multidetector computed tomography (CT) imaging for the quantification of intra-hepatic fat and thoracic adipose tissue, and coronary artery calcification (CAC) were included (n= 650). Results: Higher levels of intra-hepatic and thoracic fat were each associated with CVD risk markers. After adjustment for BMI, the associations for intra-hepatic fat with hs-CRP and insulin persisted (r= 0.21 and 0.19, respectively; P< 0.001), while those between thoracic fat indices and lipids persisted (r for total thoracic fat with HDL, LDL, and triglycerides = -0.16, 0.11, and 0.11, respectively, P< 0.05). Total thoracic fat was associated with CAC after initial multivariable adjustment (odds ratio [OR] of 2nd, 3rd, and 4th vs. 1st quartile and [95% confidence intervals]: 0.8 [0.4-1.6], 1.5 [0.8-2.9], and 1.8 [1.0-3.4]; p for linear trend = 0.017) and was only slightly attenuated after additional adjustment for BMI. Associations between total thoracic fat and CVD risk markers and CAC appeared due slightly more to associations with epicardial than pericardial fat. Conclusion: While hepatic fat is related to hs-CRP and insulin, cardiac fat is associated with subclinical atherosclerosis as demonstrated by CAC. Cardiac fat may represent a useful marker for increased CVD risk beyond the standard adiposity measures of BMI and WC.