Middle-age patients with non-alcoholic fatty liver disease (NAFLD) had a moderately higher risk of developing heart failure, an updated meta-analysis found.

Pooled data on over 11 million participants showed NAFLD to be associated with a 50% greater risk of incident heart failure over a decade (pooled random-effects HR 1.50, 95% CI 1.34-1.67, P<0.0001), reported Giovanni Targher, MD, of the University of Verona in Italy, and colleagues.

The risk was independent of sex, age, ethnicity, and common cardiovascular risk factors, such as adiposity measures, hypertension, and diabetes, the authors wrote in Gut.

Subgroup analysis also confirmed the higher risk of incident heart failure among NAFLD patients regardless of follow-up length, country of residence, or modality of heart failure diagnosis, as well as when excluding studies with diagnosis based on serum gamma-glutamyl transferase levels.

The risk also appeared to increase with the severity of NAFLD, especially among those with more extensive liver fibrosis, although this finding was based on only two studies and did not reach significance (HR 1.76, 95% CI 0.75-4.36).

“Healthcare professionals should be aware that risk of new-onset heart failure is moderately higher in patients with NAFLD,” Targher told MedPage Today. “Because of the link between the two conditions, more careful surveillance of these patients will be needed.”

The findings match up with prior research on cardiovascular disease in NAFLD, said Jamile Wakim-Fleming, MD, of the Cleveland Clinic in Ohio, who was not involved in this study. “One can also stipulate that the risks would have been much higher in the presence of multiple cardiometabolic features or biopsy-proven non-alcoholic steatohepatitis [NASH] or fibrosis.”

The chronic liver disease, NAFLD, can lead to cirrhosis, NASH, hepatocellular carcinoma, and can have various affects on the heart and vasculature, Targher’s group noted. Two prior meta-analyses had found a link between NAFLD and a higher risk of incident heart failure based on a limited number of studies.

“Our meta-analysis assessing the association between NAFLD and the long-term risk of new-onset [heart failure] is the largest and most comprehensive assessment of this association to date,” they wrote. “NAFLD not only promotes accelerated coronary atherosclerosis but also confers an increased risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain cardiac arrhythmias (mostly permanent atrial fibrillation), which may precede and/or promote the development of new-onset heart failure.”

SGLT2 and GLP-1 diabetes drugs may benefit hepatic fat content, NASH resolution, and cardiovascular outcomes, thereby reducing the risk of hospitalization for heart failure, the researchers pointed out.

Targher and colleagues examined data on 11.2 million middle-age individuals from 11 international observational cohort studies, including four from the U.S., four from Europe (Finland, Sweden, and the U.K.), and three from South Korea that were published up to March 21 of this year. A total of 2,944,058 participants had NAFLD. Overall risk of bias of the studies was medium to low.

Mean age of the participants was 55, and 50.1% were women. Mean BMI was 26. Over an average follow-up of 10 years, 97,716 experienced incident heart failure.

The authors acknowledged limitations to the data, including potential unmeasured and residual confounding. Echocardiographic data evaluating the risk of NAFLD and different left ventricular ejection fraction categories were not available. Although plasma glucose concentrations were adjusted for at baseline, no changes in the status of glucose tolerance were adjusted for at follow-up.

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