Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the U.S.

A new study on the relationship between nonalcoholic fatty liver disease (NAFLD) and heart disease found that patients with an elevated level of the enzyme associated with NAFLD had an increased risk of coronary heart disease, which appears to be related to insulin resistance, obesity and central fat distribution.

The results of this study appear in the May 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience.

NAFLD, a condition affecting up to 30 percent of the adult U.S. population, is strongly associated with predictors of heart disease, such as high cholesterol, insulin resistance, obesity and central fat distribution. Patients with NAFLD are therefore expected to have an increased risk of heart disease. However, whether or not this is the case has not been well studied to date.

Led by George Ioannou, M.D., M.S. of the Veterans Affairs Puget Sound Health Care System in Seattle, WA, researchers analyzed whether patients with suspected NAFLD who did not have viral hepatitis or consume excessive amounts of alcohol had an elevated risk of heart disease. The basis used to calculate heart disease risk was the Framingham Risk Score, a scale that takes into account age, cholesterol, blood pressure, diabetes, and smoking to predict the 10-year risk of developing heart disease. The presence of NAFLD was determined by measuring levels of alanine aminotransferase (ALT), an enzyme present in liver and heart cells that is elevated when these organs are damaged. Among the study's 7,526 patients without viral hepatitis or excessive alcohol use, 267 patients had elevated ALT activity. Researchers also analyzed 855 patients who had hepatitis or increased alcohol consumption (two potential causes of chronic liver disease) in order to rule out the possibility that liver inflammation (which is also indicated by elevated ALT) and not NAFLD might affect heart disease risk.

The results showed that patients with elevated ALT who did not have hepatitis or excessive alcohol intake had an increased risk of heart disease, particularly among women. Patients who had hepatitis or consumed excessive amounts of alcohol and were not obese did not have this increased risk. "Given that elevated serum ALT in the absence of viral hepatitis or excessive alcohol consumption is most commonly due to NAFLD in the U.S., our results suggest that NAFLD is associated with an increased risk of coronary heart disease," the authors state. They also evaluated whether there was a threshold level of ALT above which the risk of heart disease was elevated and found that it was higher in men than in women.

Although the association between NAFLD (or elevated ALT) and predictors of heart disease has been established and the link between NAFLD and increased risk of heart disease has been suggested, the current study is the first analysis that demonstrates and quantifies this risk in the U.S. population, for men and women separately, and for different thresholds of ALT. "Most of this excess calculated risk of coronary heart disease in persons with elevated ALT appears to be related to the increased prevalence of insulin resistance, obesity, and central fat distribution which are thought to be the predisposing conditions of NAFLD," the authors conclude.