Increased cardiovascular events and mortality in females with NAFLD: a meta-analysis

Non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD) share similar risk factors. Recent studies have focused on obesity and insulin resistance, but the link between NAFLD and CVD persists regardless of traditional risk factors. Despite the increased incidence and prevalence of NAFLD worldwide, there has been no thorough investigation of gender disparities nor a closer look taken into investigating the role gender may play in increased cardiovascular (CV) mortality in people with NAFLD. We assessed the incidence and prevalence of CV events and mortality based on gender in people with NAFLD, at any stage of fibrosis. A meta-regression was conducted to further analyze the impact of age on both genders. An aggregate analysis was performed on ten studies with NAFLD people. A random-effects model was used to pool the overall incidence and prevalence rates of CV events and mortality as well as all-cause mortality to examine any gender disparity. We also performed a meta-regression analysis to evaluate the effect of age on mortality for men versus women with NAFLD and CV events and mortality. Summary odds ratios (OR) and 95% confidence intervals (CI) were estimated using a random-effects model. In 108,711 people with NAFLD, of which 44% were females and 56% were males, all-cause mortality was 1.5x higher in women compared to men (OR 1.65, 95% CI 1.12-2.43, P<0.012). CV events and mortality were also 2x higher in women compared to men (OR 2.12 95% CI 1.65-2.73, P<0.001)). On meta-regression, females had higher mortality with advancing age starting at age 42 (coefficient =0.0518, P=0.00001). For people with NAFLD, women had a markedly higher incidence and prevalence of CV events, CV mortality, and all-cause mortality when compared to men. As the incidence and prevalence of NAFLD and concomitant CV events increase worldwide, we urge the medical community to increase surveillance and perform rigorous cardiovascular risk assessments for women, especially beginning at age 42. Additionally, we recommend heterogeneous surveys of gender disparities, increased focus on gender as a decisive factor for downstream CV events, the relationship between NAFLD severity and gender-based mortality differences, and larger studies representing equivalent male and female populations.