Nonalcoholic fatty liver disease and vascular function: cross-sectional analysis in the Framingham heart study

Abstract

Objective: Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk of cardiovascular disease; however, it is not known whether NAFLD contributes to cardiovascular disease independent of established risk factors. We examined the association between NAFLD and vascular function.

Approach and results: We conducted a cross-sectional study of 2284 Framingham Heart Study participants without overt cardiovascular disease who had liver fat attenuation measured on computed tomography and who had measurements of vascular function and covariates. We evaluated the association between NAFLD and vascular function using multivariable partial correlations adjusting for age, sex, cohort, smoking, diabetes mellitus, hyperlipidemia, hypertension, body mass index, and visceral adipose tissue. The prevalence of NAFLD in our sample (mean age, 52±12 years; 51.4% women) was 15.3%. In age-, sex-, and cohort-adjusted analyses, greater liver fat was modestly associated with lower flow-mediated dilation (r=-0.05; P=0.02), lower peripheral arterial tonometry ratio (r=-0.20; P<0.0001), higher carotid-femoral pulse wave velocity (r=0.13; P<0.0001), and higher mean arterial pressure (r=0.11; P<0.0001). In multivariable-adjusted models, NAFLD remained associated with higher mean arterial pressure (r=0.06; P=0.005) and lower peripheral arterial tonometry ratio (r=-0.12; P<0.0001). The association between NAFLD and peripheral arterial tonometry ratio persisted after further adjustment for body mass index and visceral adipose tissue.

Conclusions: For multiple measures of vascular function, the relationship with NAFLD appeared largely determined by shared cardiometabolic risk factors. The persistent relationship with reduced peripheral arterial tonometry response beyond established risk factors suggests that NAFLD may contribute to microvascular dysfunction.

Keywords: multidetector computed tomography; obesity; risk factors; vascular endothelium.

Figure 1. Bar chart depicting the multivariable adjusted least square means of peripheral arterial tone (PAT) ratio + standard error (SE) overall and by Body Mass Index (BMI) categories according to presence or absence of NAFLD

The BMI categories are defined as normal BMI (BMI < 25 kg/m²), Overweight (25 kg/m² ≤ BMI < 30 kg/m²) and Obese (BMI ≥ 30 kg/m²). No NAFLD represents a normal Liver Phantom Ratio (LPR) (LPR > 0.33) and NAFLD represents an abnormal LPR (LPR ≤ 0.33). Overall, PAT ratio NAFLD vs non-NAFLD p<0.0001;PAT ratio normal weight NAFLD vs non-NAFLD p=0.26; PAT ratio overweight NAFLD vs non-NAFLD p=0.0006; PAT ratio obese NAFLD vs non-NAFLD p=0.06.