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Metabolomic Study Links 13 Metabolites to Coronary Heart Disease Risk Among African Americans

NEW YORK — Researchers have identified more than a dozen metabolites linked to risk of coronary heart disease among African American individuals.

African Americans have a higher risk of developing coronary heart disease but have lower coronary artery calcium scores, a measure used to guide statin treatment among patients with intermediate risk of atherosclerotic cardiovascular disease.

To search for metabolites that might instead serve as biomarkers for coronary heart disease among African American individuals, a Harvard Medical School-led team conducted a metabolomic analysis of patient blood plasma. By examining samples from the Jackson Heart Study, which included more than 5,300 African American individuals, the researchers uncovered 13 metabolites associated with coronary heart disease, including ones not previously tied to heart disease. The new analysis appeared Wednesday in JAMA Cardiology.

"These findings may help to elucidate common and distinct metabolic processes that may be associated with CHD among individuals with different self-identified race," senior author Robert Gerszten from Harvard and colleagues wrote in their paper.

Using liquid chromatography with tandem mass spectrometry, the researchers conducted targeted metabolomic profiling of plasma samples from Jackson Heart Study participants. This cohort included 5,306 African Americans from the region around Jackson, Mississippi, of whom 2,346 developed coronary heart disease and 1,439 had coronary artery calcium scores of more than 100.

They first focused their analysis on 58 metabolites that had previously been linked to coronary heart disease in cohorts of non-Hispanic white individuals. After adjusting for factors like age, sex, diabetes status, and others, 10 of these metabolites could be replicated within the Jackson cohort.

But others had conflicting results. Leucine, for instance, was associated with a decreased risk of coronary heart disease in the Jackson cohort, even though branched-chain amino acids like it had previously been considered a biomarker of increased cardiometabolic disease risk in other studies. This finding, the researchers noted, needs additional study.

When they expanded their analysis to the full panel of 303 metabolites, they uncovered 61 metabolites associated with coronary heart disease, 46 of which were still associated with coronary heart disease after adjusting for other factors. Twenty-six metabolites, including pseudouridine, were linked to an increased risk of disease, while 20, including 1-methylnicotinamide, were linked to decreased disease risk.

Of these 61 metabolites, 43 could be assessed in the Women's Health Initiative cohort, a multiethnic dataset of 1,588 individuals. There, the link between 13 metabolites and coronary heart disease could be replicated. Nine of these metabolites, such as phosphatidylethanolamine plasmalogen, pseudouridine, and 4-acetamidobutanoate had not previously been linked to coronary heart disease or, like leucine and lysine, were in this study linked to decreased risk rather than elevated disease risk.

Another novel association between linoleoyl ethanolamide and coronary heart disease was of particular interest, the researchers noted. Linoleoyl ethanolamide, an N-acylamide, has anti-inflammatory effects on macrophages, which have a key role in atherosclerosis and coronary heart disease.

At the same time, the researchers examined whether the 46 metabolites associated with coronary heart disease after adjusting for other factors were also associated with coronary artery calcium scores, finding most were not.

"Further work is warranted to assess whether these findings are specific to African-American individuals and to identify potential mechanistic differences in the development of CHD among African-American individuals compared with individuals from other racial groups," Gerszten and colleagues wrote.

The researchers added that their study focused on the links between the metabolome and coronary heart disease, not all factors contributing to coronary heart disease disparities between African American and white individuals. But they noted that they plan to examine associations between genetic and socioeconomic factors and levels of circulating metabolites among African American individuals.