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Patients' Plasma TMAO Levels Can Predict Cardiovascular Events, Death, Study Says

NEW YORK (360Dx) – Plasma levels of the metabolite trimethylamine N-oxide can predict both near- and long-term cardiovascular events in patients with chest pain, according to a new study.

Gut microbes produce trimethylamine N-oxide (TMAO) from precursors found in red meat, eggs, and dairy products, and high levels of the metabolite have been associated with blood clots and blood vessel inflammation, suggesting that it could also be linked to major adverse cardiovascular events like heart attack, stroke, or death.

A team of researchers from the US and Switzerland measured TMAO levels in people coming to the emergency room with chest pain and correlated those levels to cardiovascular events within the following months and longer-term all-cause mortality. As they reported in the European Heart Journal this week, the researchers found that patients with higher TMAO levels were more likely to have such a major adverse cardiovascular event.

"This study shows for the first time that TMAO levels are associated with both short-and long-term risks of death and other cardiovascular problems among patients coming to hospital emergency departments with chest pain and suspected heart problems," senior author Thomas Lüscher from the University Heart Center in Zurich said in a statement.

Using liquid chromatography-mass spectrometry-based methods, Lüscher and his colleagues determined TMAO levels of blood samples from 530 patients who sought help at the Cleveland Clinic emergency department for chest pain. They then followed these patients for outcomes at 30 days, six months, and seven years.

Patients with higher plasma TMAO levels at presentation were more likely to experience a major adverse cardiovascular event in the next 30 days and in the next six months, the researchers reported. When they divided the cohort into quartiles based on their TMAO levels, the researchers found that patients in the highest TMAO quartile had a 49.6 percent frequency of major adverse cardiovascular event in the next 30 days, as compared to 30.1 percent for the quartile with the lowest TMAO levels.

In addition, they found that TMAO levels could predict risk of death. Using multivariate logistic-regression or Cox models adjusted for variables like age, gender, smoking status, and more, the researchers reported that TMAO levels were a significant predictor of a major cardiovascular event in 30 days, six months, and all-cause mortality at seven years. The highest TMAO quartile had a twofold increased hazard of mortality within seven years, as compared to the lowest quartile, the researchers noted.

Lüscher and his colleagues added that including TMAO levels as a variable alongside traditional risk factors led to a significant improvement in risk estimation.

The researchers similarly quantified TMAO levels of blood samples from an independent set of 1,683 patients with acute coronary syndrome from four different Swiss hospitals as a validation. They again found that plasma TMAO levels were higher among patients who went on to have adverse outcome; that elevated TMAO levels could predict major adverse cardiac events; and that the addition of TMAO as a variable alongside traditional risk factors improved risk estimation.

Lüscher and his colleagues noted that plasma TMAO levels were generally higher among the Cleveland cohort as compared to the Swiss group, though there was still an association between its levels and adverse events and outcomes in both groups. They suggested the disparity might be due to differences in comorbidities or diet. A vegetarian or vegan diet has been linked to lower TMAO levels, they noted.

This also suggests that TMAO levels might be modifiable through dietary changes or therapeutic interventions, the researchers said.

"TMAO offers a better understanding of the clinical impact that our daily diet has on the cardiovascular system, specifically in patients presenting with acute coronary syndrome," co-first author Slayman Obeid from University Heart Center Zurich said in a statement. "This opens the way for new preventive measures."