From the Journals

Metabolites implicated in CHD development in African Americans



Selected metabolic biomarkers may influence disease risk and progression in African American and White persons in different ways, a cohort study of the landmark Jackson Heart Study has found.

Dr. Daniel E. Cruz, an instructor at Harvard Medical School in the division of cardiovascular medicine at Beth Israel Deaconess Medical Center in Boston

Dr. Daniel E. Cruz

The investigators identified 22 specific metabolites that seem to influence incident CHD risk in African American patients – 13 metabolites that were also replicated in a multiethnic population and 9 novel metabolites that include N-acylamides and leucine, a branched-chain amino acid.

“To our knowledge, this is the first time that an N-acylamide as a class of molecule has been shown to be associated with incident coronary heart disease,” lead study author Daniel E. Cruz, MD, an instructor at Harvard Medical School in the division of cardiovascular medicine at Beth Israel Deaconess Medical Center in Boston, said in an interview.

The researchers analyzed targeted plasma metabolomic profiles of 2,346 participants in the Jackson Heart Study, a prospective population-based cohort study in the Mississippi city that included 5,306 African American patients evaluated over 15 years. They then performed a replication analysis of CHD-associated metabolites among 1,588 multiethnic participants in the Women’s Health Initiative, another population-based cohort study that included 161,808 postmenopausal women, also over 15 years. In all, the study, published in JAMA Cardiology, identified 46 metabolites that were associated with incident CHD up to 16 years before the incident event

Dr. Cruz said the “most interesting” findings were the roles of the N-acylamide linoleoyl ethanolamide and leucine. The former is of interest “because it is a lipid-signaling molecule that has been shown to have anti-inflammatory effects on macrophages; the influence and effects on macrophages are of particular interest because of macrophages’ central role in atherosclerosis and coronary heart disease,” he said.

Leucine draws interest because, in this study population, it was linked to a reduced risk of incident CHD. The researchers cited four previous studies in predominantly non-Hispanic White populations that found no association between branched-chain amino acids and incident CHD in Circulation, Stroke Circulation: Genomic and Precision Medicine, and Atherosclerosis. Other branched-amino acids included in the analysis trended toward a decreased risk of CHD, but those didn’t achieve the same statistical significance as that of leucine, Dr. Cruz said.

“In some of the analyses we did, there was a subset of metabolites that the associations with CHD appeared to be different between self-identified African Americans in the Jackson cohort vs. self-identified non-Hispanic Whites, and leucine was one of them,” Dr. Cruz said.

He emphasized that this study “is not a genetic analysis” because the participants self-identified their race. “So our next step is to figure out why this difference appears between these self-identified groups,” Dr. Cruz said. “We suspect environmental factors play a role – psychological stress, diet, income level, to name a few – but we are also interested to see if there are genetic causes.”

The results “are not clinically applicable,” Dr. Cruz said, but they do point to a need for more ethnically and racially diverse study populations. “The big picture is that, before we go implementing novel biomarkers into clinical practice, we need to make sure that they are accurate across different populations of people,” he said. “The only way to do this is to study different groups with the same rigor and vigor and thoughtfulness as any other group.”

These findings fall in line with other studies that found other nonmetabolomic biomarkers have countervailing effects on CHD risk in African Americans and non-Hispanic Whites, said Christie M. Ballantyne, MD, chief of cardiology at Baylor College of Medicine in Houston. For example, African Americans have been found to have lower triglyceride and HDL cholesterol levels than those of Whites.

Dr. Christie M. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center in Houston

Dr. Christie M. Ballantyne

The study “points out that there may be important biological differences in the metabolic pathways and abnormalities in the development of CHD between races,” Dr. Ballantyne said. “This further emphasizes both the importance and challenge of testing therapies in multiple racial/ethnic groups and with more even representation between men and women.”

Combining metabolomic profiling along with other biomarkers and possibly genetics may be helpful to “personalize” therapies in the future, he added.

Dr. Cruz and Dr. Ballantyne have no relevant relationships to disclose.

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