Heart Disease Risk Tracks Increases in Serum ALT

Women with elevated serum alanine aminotransferase (ALT) in the absence of hepatitis or excessive alcohol consumption are twice as likely to develop coronary heart disease as women with a normal liver-enzyme value.

Men with nonalcoholic fatty liver disease also have an increased likelihood of developing coronary heart disease. The 10 year risk was 10.8% for a 50-year-old man with normal serum ALT versus 13.6% if ALT was elevated, reported George Ioannou, M.D. of the VA Puget Sound Health Care System in Hepatology.

For a 50-year-old woman with normal liver enzymes the risk of developing coronary heart disease over the next 10 years was 5.9% versus 12.1% if the ALT was elevated.

But the authors suggest that it is other aspects of nonalcoholic fatty liver disease, i.e. obesity, central adiposity and insulin resistance, than really may be driving the increased risk of coronary heart disease.

After data were additionally adjusted for insulin resistance, BMI, and waist-to-hip ratio, "the adjusted mean difference in [Framingham risk score] comparing persons with elevated ALT levels with those with normal ALT levels was much reduced and no longer statistically significant (0.13, 95% CI:-0.05 to 0.3 in men; 0.32, 95% CI -0.02 to 0.7 in women)," they wrote.

Nonetheless, it is clear that the ALT bar is set lower than it is for men. Coronary heart disease risk began to climb when serum ALT was more than 30 IU/L in women versus 43 IU/L in men.

This is not the first study to link nonalcoholic fatty liver disease with an increased risk of coronary heart disease, but the study "demonstrates and quantifies this excess risk in the United States population, separately for men and women, and for different thresholds of ALT level," the authors wrote.

Dr. Ioannou and colleagues performed a cross-sectional analysis comparing participants in the serum ALT in 7,526 participants in the Third National Health and Nutrition Examination Survey who had no viral hepatitis and no history of excessive alcohol consumption.

Two hundred sixty-seven participants had elevated serum ALT and those with elevated ALT were younger and more likely to be male than those with normal ALT.

After adjusting for sex and age, those with elevated ALT had higher total cholesterol, lower HDL, and higher blood pressure (systolic and diastolic) than those with normal ALT levels. Moreover, those with elevated ALT were more likely to be diabetic compared to those with normal ALT values.

The authors noted several limitations of the study. The cause of the increased serum ALT was assumed to be nonalcoholic fatty liver disease but was not confirmed with liver biopsies. The Framingham risk score was used to predict the risk of future coronary heart disease rather than follow the participants in time to determine the actual occurrence of coronary heart disease.