Abstract

Background: Computed tomography (CT) attenuation of abdominal fat as measured by Hounsfield units (HU) is associated with the composition of fat such as adipocyte size, vascularity, and fibrosis and has been associated with varying degrees of cardiometabolic risk. The objective of this study was to determine if fat quality, evaluated by CT attenuation of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), is prospectively associated with incident cardiovascular disease (CVD) and all cause mortality outcomes independent of absolute VAT and SAT volumes. Methods: Participants were drawn from offspring and third-generation cohorts from the multidetector computed tomography sub-study of the Framingham Heart Study (n=3324, 48% women, mean age of 51 years). SAT and VAT volumes were acquired by manually outlining the abdominal muscular wall separating the visceral from the subcutaneous fat depot. The average HU of each depot were recorded. Cardiovascular risk factors were measured using standard definitions. The outcomes of interest were incident CVD, all cause mortality, non-cardiovascular deaths and cancer deaths. Information on cause of death was obtained from death certificates, medical records and family members. Cox proportional hazard models were used to determine the association between VAT and SAT HU and the outcomes of interest. We adjusted for standard CVD risk factor covariates, secondarily for BMI, and then for VAT or SAT volumes. Results: There were a total of 111 incident CVD events, 85 deaths including 69 non-cardiovascular deaths and 45 cancer deaths in up to 23,047 person-years of follow-up. A one standard deviation (SD) increment in VAT attenuation was associated with a multivariable adjusted hazard ratio (HR) for all cause mortality of 1.40 (95% CI 1.12-1.75, p=0.003), which was strengthened after additional adjustment for BMI (HR 1.53, 95% CI 1.21-1.93, p<0.001) and VAT volume (HR 1.99, 95% CI 1.47-2.69, p<0.001). Non-cardiovascular death accounted for the majority of this trend and remained significant in all three models, including after adjustment for VAT volume (HR 1.97, 95% CI 1.42-2.75, p<0.001). More specifically VAT HU was associated with cancer deaths (HR 1.96, 95% CI 1.29-2.98, p=0.001). Conversely, we observed no association between VAT HU and incident CVD in the multivariable model (HR 0.83, 95% CI (0.67, 1.04) p=0.11) or after additional adjustment for BMI or VAT volume. Similar results were found for SAT HU. Conclusions: CT attenuation of both VAT and SAT is associated with all-cause mortality, non-cardiovascular death and cancer death. These associations highlight how indirect indices of fat quality can potentially add to our understanding of the complications of obesity.

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