Abdominal adipose tissue depots and cardiometabolic disease risk in postmenopausal women

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PROJECT SUMMARY Accumulating basic, clinical, and population research suggests that high amounts of abdominal fat, particularly visceral adipose tissue (VAT) in the intra-abdominal depot, plays a crucial role in the pathophysiology of cardiometabolic diseases (i.e. type 2 diabetes (T2D), cardiovascular diseases (CVD) and stroke). This research has elegantly described the intimate nature of VAT as a powerful metabolic driver of insulin resistance, dyslipidemia, and hypertension. It also suggests that total body fat, and more specifically subcutaneous adipose tissue (SAT), may be relatively less important or even benign in the pathophysiology of cardiometabolic disease. Despite this burgeoning framework of knowledge, much remains unknown about the relationship between abdominal VAT and SAT levels with incident cardiometabolic disease events – a critical gap in the evidence base since further insight resulting from research on this topic would have major implications related to the importance of body composition and obesity in cardiometabolic disease prevention. The central reason for the bottleneck in the evidence base has been feasibility. Researchers and clinicians have had to rely on imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) to measure specific adipose tissue depots. Issues such as cost, radiation, and availability have made these methods impractical in the clinic and for large research studies; and the few studies which have incorporated these technologies may have limited sample size, or have not accrued enough follow up time and events to adequately address the topic. However, there is an efficient and economical solution to this problem via the application of new technology that quantifies abdominal VAT and SAT from existing Dual Energy X-Ray Absorptiometry (DXA) scans. This technology has demonstrated strong validity with gold-standard measures of abdominal adipose tissue depots from MRI and CT scans. Therefore, we propose to apply this novel technology to the existing Women's Health Initiative (WHI) DXA cohort to quantify abdominal VAT and SAT from existing DXA scans. This proposal will create a valuable, new, minority enriched, analytic longitudinal cohort that will utilize repeated DXA measurements in the WHI at baseline (N=10,607), year 3 (N=8,939), year 6 (N=8,239), and year 9 (N=4,595) to address essential questions on the topic of abdominal adiposity/body composition, and cardiometabolic disease risk in postmenopausal women as they age. This project capitalizes on a rich scientific resource and will provide new and advanced results that will delineate the importance of abdominal adipose tissue depots in cardiometabolic disease risk and the potential for targeted interventions and prevention efforts.