1 Association Between Visceral and Subcutaneous Adipose Depots and Incident Cardiovascular Disease Risk Factors Running title: Abraham et al.; VAT-SAT and Incident CVD Risk Factors

2 Background—Visceral and subcutaneous adipose tissue (VAT and SAT) vary in volume and quality. We evaluated whether fat volume or attenuation (indirect measure of quality) predicts metabolic risk factor changes. Methods and Results—Framingham Heart Study Multi-detector Computed Tomography Substudy participants (n=1730, 45 % women) were followed over a mean of 6.2 years. Baseline VAT and SAT volume (in cm3) and attenuation (in Hounsfield units, HU) were assessed. Outcomes included blood pressure, lipids and glucose. We constructed multivariable regression models predicting change from baseline to follow-up. Baseline VAT was associated with metabolic risk factors at follow-up. Per 500 cm3 increment in baseline VAT, glucose was 2.34 mg/dL higher (95 % CI 1.71-2.97) and HDL was 1.62 mg/dL lower (95 % CI 0.97-2.28) in women (p<0.0001 for both). These findings remained significant after adjustment for BMI. Results for SAT were similar, although less striking. Lower (more negative) fat attenuation was associated with more adverse metabolic profiles at follow-up. For example, per 5 unit decreas