Patients diagnosed with nonalcoholic fatty liver disease (NAFLD) have an increased risk for fatal and nonfatal cardiovascular disease (CVD) events, according to a systematic review and meta-analysis published in Lancet Gastroenterology Hepatology.

Investigators pooled data from 36 unique, longitudinal studies that assessed the relationship between NAFLD and CVD events. Nearly 6 million patients were represented by the included studies.

The primary outcome of the review was the incidence of fatal or nonfatal CVD events, or both, in patients with NAFLD compared against patients without NAFLD as controls. Additionally, the correlation between the incidence of CVD events and the severity of NAFLD disease was assessed.

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Of the 5,802,226 individuals included in the studies, 49.8% were men with a mean age of 53 years. Mean body mass index (BMI) was 27.7 kg/m2. In total, 335,132 individuals had been diagnosed with NAFLD at baseline and there were 99,668 reported cases of fatal and nonfatal CVD events over a median follow-up of 6.5 years.

Patients with NAFLD were at higher risk for fatal CVD events, nonfatal CVD events, and both events, compared with non-NAFLD control patients, with a pooled hazard ratio (HR) of 1.45 (95% CI, 1.31-1.61; P <.0001). The analysis was independent of additional risk factors such as age, sex, and BMI. CVD event risk increased in proportion to severity of NAFLD. Severe NAFLD had the most notable risk, with an HR of 2.50 (95% CI, 1.68-3.72; P =.0004).

While most of the included studies adjusted their results to account for confounding factors, it is possible that there may still be unaccounted influence. Additional research is needed to understand the relationship between NAFLD and CVD.

Despite these limitations, the authors believe “the complex interplay between the liver and cardiometabolic risk factors in NAFLD highlights an urgent need for a person-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiometabolic risk.”


Mantovani A, Csermely A, Petracca G, et al. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(11):903-913. doi: 10.1016/S2468-1253(21)00308-3

This article originally appeared on Gastroenterology Advisor