Introduction: Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk for cardiovascular (CV) related-death. Prior studies have demonstrated a cross-sectional association between NAFLD and CV risk factors including hypertension, hyperlipidemia, and insulin resistance. Little is known about the relationship between NAFLD and incident CV risk factors in the American adult population. We hypothesized that, independent of overall adiposity, NAFLD is associated with incident CV risk factors.
Methods: We conducted a longitudinal study of 1,645 Framingham Heart Study Third Generation Cohort participants (median age 44.0 years, 46.1% women) who attended examination 1 (2002-2005) and examination 2 (2008-2011) and participated in the multi-detector computed tomography (MDCT) sub-study (2002-2005). The median follow up duration was 6.2 years. We excluded participants with heavy alcohol use or with prevalent myocardial infarction and stroke at baseline. Liver fat was assessed using MDCT at the baseline examination. Odds ratios (OR) of incident CV risk factors per standard deviation increase of liver fat were estimated using logistic regression models with adjustment for multiple baseline covariates including BMI.
Results: The prevalence of NAFLD was 16.6% in the present sample. In multivariable-adjusted models, liver fat was not associated with incident metabolic syndrome (OR 1.10, 95%CI: 0.88, 1.37), hypertriglyceridemia (OR 0.93, 95%CI: 0.75, 1.16), low high-density lipoprotein (OR 1.21, 95%CI: 0.88, 1.66), or prediabetes (OR 1.15, 95%CI: 0.95, 1.40). However, per standard deviation increase of liver fat, we observed a greater risk of incident hypertension (OR 1.22, 95%CI: 1.02-1.46, P-value=0.03) and incident type 2 diabetes (OR 1.45, 95%CI: 1.15-1.84, P-value=0.002). The association with liver fat and incident type 2 diabetes remained after additional adjustment for visceral adipose tissue volume (OR 1.42, 95%CI: 1.10-1.82, P-value=0.006).
Conclusions: The present study demonstrates that higher level of liver fat is associated with increased incidence of hypertension and type 2 diabetes over 6 years. Future studies are needed to determine if interventions targeting individuals with NAFLD may reduce incident CV risk factors burden.