MONDAY, OCT. 27, 2014, Cleveland: A chemical byproduct of intestinal bacteria-dependent digestion, TMAO (trimethylamine N-oxide) – already proven to contribute to heart disease and to be an accurate tool for predicting future heart attacks, stroke and death – has for the first time been linked to heart failure and worse long-term prognosis for those patients, according to Cleveland Clinic research published today in the Journal of the American College of Cardiology.
The research team was led by Stanley Hazen, M.D., Ph.D., Chair of the Department of Cellular and Molecular Medicine for the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute at Cleveland Clinic, and W.H. Wilson Tang, M.D., Department of Cardiovascular Medicine in the Miller Family Heart and Vascular Institute and Lerner Research Institute.
Drs. Hazen and Tang followed 720 heart failure patients over a five-year period and found that higher TMAO levels predicted higher future risk of death from heart failure, independent of other clinically used blood tests or risk factors. Interestingly, patients who had high levels of natriuretic peptides (an indicator of advanced heart failure) but low levels of TMAO had a much lower mortality rate than individuals with elevated levels in both markers. The researchers also found that when both TMAO and BNP (a peptide typically measured in heart failure patients) levels were raised, patients had more than a 50 percent mortality rate over 5 years.
TMAO, the researchers previously found, is produced when intestinal bacteria digest certain dietary components that are found in red meat, egg yolks, liver and some energy supplements. They found in a large clinical study that high levels of TMAO can predict future adverse outcomes like heart attack, stroke, and death.
"I am excited that these studies suggest TMAO testing may not only help identify those patients at greatest risk and for whom more aggressive monitoring is needed, but also that TMAO testing may help to tailor dietary efforts to the individual in the hopes of reducing future risks among those high-risk subjects," said Dr. Hazen.
"Our new results suggest that understanding why TMAO levels are elevated in the setting of heart failure may provide important insights into how intestinal bacteria contribute to disease progression in heart failure," said Dr. Tang.
According to the Centers for Disease Control and Prevention, heart failure occurs when weakened heart muscles do not pump blood effectively. More than 5 million patients in the United States are affected, costing the U.S. approximately $32 billion each year.
The current study is an extension of Drs. Hazen and Tang's previous work, in which they found TMAO is linked to increased risk of heart disease, even in the absence of known cardiovascular risks, and is produced when intestinal bacteria digest carnitine, found in red meat and some energy drinks, and the nutrient phosphatidylcholine, commonly known as lecithin. The prior research showed that higher TMAO levels in the blood were associated with poorer outcomes in heart disease. Dr. Hazen and colleagues have now confirmed that gut flora are essential in forming TMAO in humans and demonstrated a relationship between TMAO levels and future cardiac events like heart attack, stroke, and death—even in those with no prior evidence of cardiac disease risk.
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This research was supported by grants from the National Institutes of Health and the Office of Dietary Supplements (grants R01HL103866, 1P20HL113452).
Dr. Hazen is listed as a co-investigator on pending and issued patents held by Cleveland Clinic relating to cardiovascular diagnostics.
About Cleveland Clinic
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S.News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. More than 3,000 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. The Cleveland Clinic health system includes a main campus near downtown Cleveland, more than 75 Northern Ohio outpatient locations, including 16 full-service Family Health Centers, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and, currently under construction, Cleveland Clinic Abu Dhabi. In 2012, there were 5.1 million outpatient visits throughout the Cleveland Clinic health system and 157,000 hospital admissions. Patients came for treatment from every state and from more than 130 countries. Visit us at http://www.clevelandclinic.org.
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About the Lerner Research Institute
The Lerner Research Institute (LRI) is home to laboratory, translational and clinical research at Cleveland Clinic. Its three-part mission is: to promote human health by investigating the causes of disease and discovering new approaches to prevention and treatments, to train the next generation of biomedical researchers and to foster collaborations with clinical care providers. LRI's total annual research expenditure was $255 million in 2012 (nearly $110 million in federal funding). With more than 700,000 square feet of lab, office, and core services space, LRI is home to more than 2,000 people working in disease-focused research programs. In 2012, LRI researchers published over 600 articles in high-impact biomedical journals (top 10 percent) and generated 83 invention disclosures, 10 new licenses and 35 patents. LRI faculty oversee curriculum and teach courses in the Cleveland Clinic Lerner College of Medicine (CCLCM) of Case Western Reserve University and participate in doctoral programs, including the Molecular Medicine PhD Program, supported in part by the Howard Hughes Medical Institute.
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Journal
Journal of the American College of Cardiology