Biopsy-proven NAFLD associated with higher rates of MACE

Patients in a Swedish study whose nonalcoholic fatty liver disease (NAFLD) was confirmed on biopsy were more likely to experience incident major adverse cardiovascular events (MACE).

Major adverse cardiovascular events (MACE) may be more common in adults with nonalcoholic fatty liver disease (NAFLD) of any severity compared to those without NAFLD, according to a recent study.

Researchers performed a population-based cohort study in which all Swedish adults from 1966 to 2016 with histologically confirmed NAFLD but no cardiovascular disease (CVD) were matched to five or fewer population controls without NAFLD or CVD. NAFLD was categorized as simple steatosis, nonfibrotic steatohepatitis, noncirrhotic fibrosis, and cirrhosis. The study's primary outcome was incident MACE, defined as ischemic heart disease, stroke, congestive heart failure, or cardiovascular mortality. Results were published online Sept. 6 by Gut.

The study included 10,422 patients with NAFLD and no CVD and 46,517 controls matched by age, sex, calendar year, and county. A total of 2,850 patients with NAFLD and 10,648 controls had confirmed incident MACE over a median of 13.6 years. MACE incidence was higher in patients with NAFLD than in controls (24.3 per 1,000 person-years vs. 16.0 per 1,000 person-years; difference, 8.3 per 1,000 person-years; adjusted hazard ratio [HR], 1.63 [95% CI, 1.56 to 1.70]). Rates of individual MACE, including ischemic heart disease, congestive heart failure, stroke, and cardiovascular mortality, were also higher among patients with NAFLD. A progressive increase in incident MACE rates was observed with worsening NAFLD, peaking for cirrhosis (adjusted HR for patients vs. controls, 2.15; 95% CI, 1.77 to 2.61).

The study was retrospective and could be subject to selection bias and residual confounding, among other limitations, the authors noted. They concluded that all NAFLD is associated with increased risk for fatal and nonfatal MACE and that the risk worsens with disease severity. The results “provide support for improved [cardiovascular] screening and risk stratification strategies in high-risk patients with NAFLD fibrosis and cirrhosis who may be most likely to benefit from primary CVD prevention.”

An accompanying commentary said the study convincingly illustrates the relationship between NAFLD and CVD risk, confirming results of a previous meta-analysis and providing new evidence of a link between NAFLD and congestive heart failure. “During the last decade, evidence has accumulated to show that NAFLD is a ‘multisystem’ disease that not only increases risk of liver-related complications, but also increases risk of developing type 2 diabetes mellitus (T2DM), chronic kidney disease, and certain extrahepatic cancers,” the commentary authors wrote. “Overall, therefore, these data provide important evidence supporting a holistic approach to the treatment of NAFLD, where not only is the management and treatment of liver disease considered, but also the increased risk of CVD and other extrahepatic complications.”