SAN FRANCISCO — Recent research indicates that liver disease independently drives cardiovascular disease, Dr. Arun J. Sanyal said at the Third World Congress on Insulin Resistance Syndrome.
This relationship is so striking that Dr. Sanyal maintained, only half in jest, that “the liver is the boss of the heart.”
“The chicken-and-egg relationship between insulin resistance and hepatic steatosis can have potential effects at the level of the endothelium, platelet aggregability, and atherosclerosis, all of which combine to produce cardiovascular disease,” said Dr. Sanyal of Virginia Commonwealth University, Richmond.
One longitudinal study demonstrated that altered liver enzymes predict the development of metabolic syndrome (Diabetes 2005;54:3140–7).
Among 633 subjects who were free of metabolic syndrome at baseline, 127 developed metabolic syndrome within 5 years.
Multivariate logistic regression models adjusting for age, sex, ethnicity, and alcohol consumption showed that subjects in the upper quartiles of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALK) were at significantly increased risk of incident metabolic syndrome, compared with those in the lowest quartile.
Another study looked at endothelial function in 52 patients with nonalcoholic fatty liver disease (NAFLD) and 28 age- and sex-matched controls (Hepatology 2005;42:473–80). Compared with controls, patients with NAFLD had a significantly lower vasodilatory response of the brachial artery in response to ischemia. This response was significantly worse in patients with nonalcoholic steatohepatitis (NASH) than those with pure fatty liver.
In addition, the 10-year risk of coronary events as calculated by the Framingham equation was significantly worse in patients with NAFLD than in controls.
A third, longitudinal, study examined the relationship between gamma-glutamyltransferase (GGT) and incident hypertension (Hypertension 2005;46:1186–93). Among 897 patients with normal GGT values, those in the highest quintile of normal were more than twice as likely to develop hypertension over 6 years than were those in the lowest quintile. The investigators noted that the association between GGT and hypertension was present in both current and noncurrent drinkers, but only if they were above the mean in body mass index, waist circumference, and abdominal height.
This suggests that the association between GGT and hypertension is not due solely to alcohol consumption, and that fatty liver may represent an underlying mechanism of the association.
A fourth study used 4,222 normal subjects without cirrhosis or hepatitis B or C and examined the relationship between hepatic steatosis and carotid plaques (World J. Gastroenterol. 2005;11:1848–53).
After adjusting for confounding factors, the investigators determined that individuals with fatty liver had carotid plaques more often than did those without fatty liver. They hypothesized that this phenomenon may be explained by metabolic changes from nonalcoholic fatty liver disease.
Despite this accumulating evidence, Dr. Sanyal called for more research on the underlying mechanisms of the relationship between fatty liver, metabolic syndrome, and cardiovascular disease.
“This will give us terrific targets to identify new ways of addressing this atherosclerotic disease in patients who also have fatty liver disease,” he said.
This will give us new ways of addressing atherosclerotic disease in patients who also have a fatty liver. DR. SANYAL