Associations of Hepatosteatosis With Cardiovascular Disease in HIV-Positive and HIV-Negative Patients: The Liverpool HIV-Heart Project

BACKGROUND Hepatosteatosis (HS) has been associated with cardiovascular disorders in the general population. We sought to investigate whether HS is a marker of cardiovascular disease (CVD) risk in HIV-positive individuals, given that metabolic syndrome is implicated in the increasing CVD burden in this population. AIMS To investigate the association of HS with CVD in HIV-positive and HIV-negative individuals. METHODS AND RESULTS We analyzed computed tomography (CT) images of 1306 subjects of whom 209 (16%) were HIV-positive and 1097 (84%) HIV-negative. CVD was quantified by the presence of coronary calcification from both dedicated cardiac CT and nondedicated thorax CT. HS was diagnosed from CT data sets in those with noncontrast dedicated cardiac CT and those with venous phase liver CT using previously validated techniques. Previous liver ultrasound was also assessed for the presence of HS. The HIV-positive group had lower mean age (P < 0.005), higher proportions of male sex (P < 0.005), and more current smokers (P < 0.005). The HIV-negative group had higher proportions of hypertension (P < 0.005), type II diabetes (P = 0.032), dyslipidemia (P < 0.005), statin use (P = 0.008), and HS (P = 0.018). The prevalence of coronary calcification was not significantly different between the groups. Logistic regression (LR) demonstrated that in the HIV-positive group, increasing age [odds ratio (OR): 1.15, P < 0.005], male sex (OR 3.37, P = 0.022), and HS (OR 3.13, P = 0.005) were independently associated with CVD. In the HIV-negative group, increasing age (OR: 1.11, P < 0.005), male sex (OR 2.97, P < 0.005), current smoking (OR 1.96, P < 0.005), and dyslipidemia (OR 1.66, P = 0.03) were independently associated with CVD. Using a machine learning random forest algorithm to assess the variables of importance, the top 3 variables of importance in the HIV-positive group were age, HS, and male sex. In the HIV-negative group, the top 3 variables were age, hypertension and male sex. The LR models predicted CVD well, with the mean area under the receiver operator curve (AUC) for the HIV-positive and HIV-negative cohorts being 0.831 [95% confidence interval (CI): 0.713 to 0.928] and 0.786 (95% CI: 0.735 to 0.836), respectively. The random forest models outperformed LR models, with a mean AUC in HIV-positive and HIV-negative populations of 0.877 (95% CI: 0.775 to 0.959) and 0.828 (95% CI: 0.780 to 0.873) respectively, with differences between both methods being statistically significant. CONCLUSION In contrast to the general population, HS is a strong and independent predictor of CVD in HIV-positive individuals. This suggests that metabolic dysfunction may be attributable to the excess CVD risk seen with these patient groups. Assessment of HS may help accurate quantification of CVD risk in HIV-positive patients.