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NAFLD may increase risk for cardiovascular disease, mortality

Steatosis was an independent risk factor for atherosclerosis in a retrospective study, suggesting that patients with nonalcoholic fatty liver disease may have an increased risk for early cardiovascular disease and mortality.

“Evidence indicates that the fatty and inflamed liver expresses several pro-inflammatory and procoagulant factors, as well as genes involved in accelerated atherogenesis,” Raluca Pais, MD, PhD, of the Pierre and Marie Curie University, INSERM, and the CDR Saint Antoine, Institute of Cardiometabolism and Nutrition, France, said in a press release. “This raises the possibility that the link between NAFLD and cardiovascular mortality might not simply be mediated by shared, underlying, common risk factors, but rather that NAFLD independently contributes to increasing this risk,” Vlad Ratziu, MD, PhD, professor at Pierre and Marie Curie University, also said in the release.

The researchers evaluated 5,671 patients presenting with at least two cardiovascular risk factors seen at a cardiovascular prevention center in France between 1995 and 2012. Each patient underwent carotid ultrasound with measurement of carotid intima-media thickness (C-IMT) and carotid plaques, to determine whether NAFLD is an incidental or direct cause of atherosclerosis of the carotid arteries. Steatosis was measured using the Fatty Liver Index, a biomarker panel for NAFLD.

Thirty-three percent of the patients had a Fatty Liver Index score of at least 60 and were determined to have steatosis. These patients were older, had higher BMI, higher prevalence of type 2 diabetes and higher aminotransferase levels compared with those without steatosis. In addition, patients with steatosis had higher C-IMT and 10-year Framingham Risk Score compared with those who did not have steatosis.

The researchers further examined steatosis impact on C-IMT and Framingham Risk Score when considering cardiovascular risk factors, such as diabetes. They found that although patients with diabetes and without diabetes had different C-IMT values (0.63±0.15 mm vs. 0.61±0.13 mm; P < .001), this difference was no longer observed when taking steatosis into consideration, according to the research. In patients with type 2 diabetes or dyslipidemia, those with steatosis had higher C-IMT compared with those without steatosis (0.64±0.14 mm vs. 0.61±0.14 mm; P < .001).

“In contrast, in patients with steatosis, the diabetes and dyslipidemia status were not associated with increased C-IMT, suggesting that steatosis impacted to a larger extent pre-atherosclerotic lesions than diabetes or dyslipidemia,” the researchers wrote.

The researchers noted that Framingham Risk Score was higher in patients with type 2 diabetes and dyslipidemia regardless of presence of steatosis.

In a longitudinal study of 1,872 patients with available data after 8 years, 12% developed steatosis and 23% developed carotid plaque, suggesting that patients with fatty liver were at increased risk for developing carotid plaque over time. C-IMT increased in patients with steatosis. However, this did not change in patients without steatosis.

“We found that patients with steatosis, but not overweight, not type 2 diabetic, or without arterial hypertension, are at higher risk of developing these complications than individuals without steatosis. This indicates that NAFLD is a precursor of metabolic syndrome,” Pais said in the release, adding that “regardless of the mechanisms involved, the clinical implications are of critical importance since patients at cardiovascular risk presenting with one or more metabolic syndrome characteristics are at even greater risk if they have steatosis.”

It is “not surprising” that NAFLD plays a key role in cardiovascular disease, Leon Adams, MBBS, PhD, of the University of Western Australia School of Medicine and Pharmacology, and Quentin M. Anstee, BSc, MBBS, PhD, MRCP, of the Liver Research Group, Institute of Cellular Medicine and The Medical School at Newcastle University, United Kingdom, wrote in an accompanying editorial.

“Nonalcoholic fatty liver disease typically exists in a milieu of disturbed metabolism, including increased total body adiposity, insulin resistance, impaired glucose tolerance and dyslipidemia. Cumulatively these factors increase the risk for cardiovascular disease, and so it is not surprising [cardiovascular disease] is the leading cause of death in NAFLD patients,” they wrote.

“Clinicians should be aware of the increased cardiovascular risk in patients with NAFLD and consequently screen for conventional cardiovascular risk factors and use accepted risk calculators to make decisions regarding preventative pharmacotherapy, including statins.”

Disclosure: The researchers, Adams and Anstee report no relevant financial disclosures.