NAFLD May Be Independent Risk Factor for CV Morbidity and Mortality

NAFLD May Be Independent Risk Factor for CV Morbidity and Mortality

NEW YORK (Reuters Health) – The association between non-fatty alcoholic liver disease (NAFLD) and increased cardiovascular disease (CVD) risk is further increased with higher fibrosis stage, suggesting that NAFLD may be an independent risk factor for CVD morbidity and mortality, researchers say.

As reported in The Lancet Gastroenterology and Hepatology, Dr. Giovanni Targher of Universitaria Integrata and colleagues in Verona did a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of incident CVD events.

Thirty-six longitudinal studies were included, with aggregate data on 5.8 million individuals (mean age 53 years) and 99,668 incident cases of fatal and non-fatal CVD events over a median follow-up of 6.5 years.

NAFLD was associated with a moderately increased risk of fatal or non-fatal CVD events (pooled random-effects HR, 1.45). The risk markedly increased across the severity of NAFLD, especially the stage of fibrosis (pooled random-effects HR, 2.50).

All risks were independent of age, sex, adiposity measures, diabetes, and other common cardiometabolic risk factors.

Further, sensitivity analyses did not change the results.

The authors state, “These findings call for a more active and systematic search for cardiovascular disease among individuals with NAFLD with a view to potential earlier treatment and referral to a cardiologist.”

Dr. Maria Del Ben of Sapienza University, coauthor of a related editorial, commented in an email to Reuters Health, “NAFLD has been traditionally interpreted as a liver disease, which over time can progress towards liver-related fatal and non-fatal complications. However, patients also have an increased chance of developing cardiovascular diseases, which represent the first cause of death in this clinical setting and seem to be correlated with greater severity of liver fibrosis.”

“Most patients usually have been referred to gastroenterologists and hepatologists who currently, unfortunately, do not yet have effective therapies to slow the progression of liver damage,” she said. “By contrast, effective cardiovascular protection can be given to NAFLD patients, and treatment of comorbidities and risk factors must become a priority in the care of these patients. Intensive treatment of diabetes, metabolic syndrome, hyperlipidemias, and obesity is of paramount importance.”

“A more holistic approach, including diabetologists, internists, cardiologists, and nutritionists is strongly recommended, rather than just a liver-centered approach,” she said. “This will be the main challenge to providing overall protection to patients with NAFLD.”

Dr. Anurag Maheshwari of Mercy’s Institute for Digestive Health and Liver Disease in Baltimore told Reuters Health by phone that the results mirror his clinical experience. “We have long seen a higher risk of cardiovascular events in patients who have fatty liver. We think that the underlying factor here is metabolic syndrome.”

“We have a cardiovascular risk score, where we calculate the risk of cardiovascular illness for a patient based on specific risk factors,” he said. “I think this study sends the message that we probably should incorporate the presence or absence of NAFLD in the cardiovascular risk score. Also, if we see people who have high severity NAFLD, should we be doing stress tests on these patients, regardless of whether they have any symptoms, in order to identify early-stage coronary artery disease? I think that’s a bit of a reach now, but it could be a focus for further research.”

Dr. Cynthia Kos, a cardiologist and advanced heart failure specialist at Deborah Heart and Lung Center in Brown Mills, New Jersey, commented by email, “Amongst the studies reviewed in this analysis, the severity of NAFLD was not defined by a universal technique. Some studies utilized ultrasonographic scores, will others utilized histopathology of liver biopsies, and not all were compared with controls. It is unclear if subjective heterogeneity of these interpretations had any impact on the ultimate conclusion of this study.”

“Although I have not had a patient referred to me solely based on the premise of this study – i.e., that they would have increased CV risk given presence of NAFLD – studies such as this have the potential to garner interest from cardiologists, especially if the evidence suggests that a novel CV risk factor is emerging.”

Dr. Targher declined to provide a comment.

SOURCE: and The Lancet Gastroenterology and Hepatology, online September 20, 2021.

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