Gut-Flora Metabolite Biomarker for Cardiac Risk
Heart & Vascular Institute Physician eNewsletter - Fall/Winter 2014
A test for trimethylamine-N-oxide (TMAO), a gut flora-dependent metabolite that contributes to heart disease, was voted one of the top 10 medical innovations of 2014 at Cleveland Clinic’s 10th annual Medical Innovation Summit, held October 14-16, 2013 at the Global Center for Health Innovation in downtown Cleveland. The meeting convened more than 1,100 medical thinkers and leaders for candid discussion on new medical technology, its future, recent breakthroughs and continuing challenges. In preparation for the meeting, 110 Cleveland Clinic experts contributed their opinions on which new technologies would likely have the biggest impact on patient care in 2014. The TMAO assay was one of 150 nominations for the award.
TMAO is a metabolite produced by the liver after intestinal bacteria have digested animal protein. Its value as a novel biomarker of increased cardiac risk was identified by Stanley L. Hazen, MD, PhD, Vice Chairman of Translational Research at the Lerner Research Institute and Section Head of Preventive Cardiology and Rehabilitation at Cleveland Clinic. In two clinical studies collectively involving more than 6,500 subjects, TMAO was able to predict cardiac risk in patients whose risk had not been identified by traditional risk factors and blood tests. In these studies, patients with the highest TMAO levels were two to 2 ½ times more likely to have a cardiac event than those with the lowest blood levels of the biomarker.
The assay is now available through LipoScience for use in clinical trials.
“The concept that gut flora contribute to heart disease is very exciting and opens up new avenues for intervention,” says Dr. Hazen, principal author of the clinical studies published in The New England Journal of Medicine in April and in Nature Medicine in May 2013.
Reinforcing the effects of dietary choices
In these studies, Dr. Hazen and his colleagues showed that bacteria in the digestive tract turn choline, a byproduct of lecithin, found meat and eggs, into trimethylamine. This produced is absorbed into the bloodstream and metabolized by the liver. The resulting substance is TMAO. In 4,000 patients who underwent coronary angiography, a relationship between TMAO levels and future (3-year) risk of major adverse cardiovascular events, such as heart attack, stroke and death, was clearly seen.
When study participants were given antibiotics prior to eating eggs—an abundant source of choline—gut bacteria levels and, subsequently, TMAO levels, did not increase.
The second study followed the gut flora metabolism of carnitine into TMAO in more than 2,500 subjects. Carnitine is a nutrient abundant in red meat, and was shown to similarly promote TMAO formation, accelerated atherosclerosis in animal models, and was also associated with incident major adverse cardiac events in patients.
“One day, we expect that testing for TMAO levels may help us individualize dietary recommendations,” says Dr. Hazen.
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