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Study identifies four metabolites related to CHD risk
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ANAHEIM, Calif. — Low levels of four specific metabolites were found to be associated with risk for incident CHD, according to new research from the BiomarCaRE consortium presented at the American Heart Association Scientific Sessions.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” Tanja Zeller, PhD, professor of genomics and systems biology at Universitäres Herzzentrum Hamburg GmbH in Germany, said during a presentation.
Zeller and colleagues aimed to identify novel biomarkers to improve CHD risk estimation and investigated metabolites, whose changes appear to be linked to pathological conditions.
“The objectives were to study the association between circulating metabolome and incident coronary heart disease, and to investigate the performance of coronary heart disease-associated metabolomic combinations across large population-based cohorts from the BiomarCaRE consortium,” she said.
The researchers analyzed 10,741 individuals (mean age, 56 years; 39% women), 2,166 of whom had incident CHD, and 141 metabolites. Analyses were adjusted for BMI, systolic BP, diabetes, total cholesterol, sex, smoking, study site and age at examination. Significance was defined as a P value of < .05 and Bonferroni correction.
According to results presented here, 24 metabolites were associated with incident CHD, with a P value of < .05. After Bonferroni correction, low levels of four metabolites remained associated with incident CHD, Zeller said. Those metabolites, which are phosphatidylcholines, are:
- PC ae C40:6 (HR for incident CHD = 1.34; 95% CI, 1.19-1.52);
- PC ae C38:6 (HR = 1.23; 95% CI, 1.11-1.36);
- PC aa C38:5 (HR = 1.21; 95% CI, 1.1-1.34); and
- PC aa C38:6 (HR = 1.15; 95% CI, 1.07-1.24).
Zeller noted that combining the four metabolites into a metabolite panel yielded a similar result.
For all four metabolites, the association was significant in both sexes but slightly more pronounced in women, she said.
Further analysis determined that people in the lowest tertile of phosphatidylcholine levels had higher HRs for incident CHD compared with people in the middle and highest tertiles, Zeller said.
The strength of the association was similar to that of classical risk factors, she said. – by Erik Swain
Reference:
Zeller T, et al. LBS.04 – Sweet Spot in Cardiometabolic Care. Presented at: American Heart Association Scientific Sessions; Nov. 11-15, 2017; Anaheim, California.
Disclosure: Zeller reports no relevant financial disclosures.
Perspective
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Kiran Musunuru, MD, PhD, MPH
This is one of the first large-scale studies to look at a group of molecules called metabolites — meaning that they are produced by the body's metabolism — in the bloodstream and to ask whether certain metabolites correlate with risk for heart disease. This is different from previous studies that looked at genes, which remain the same throughout a person's lifetime, because metabolites can change over time in response to lifestyle choices and environmental exposures. We already knew that certain genes are associated with a higher risk for heart disease. This study now shows that the levels of four specific metabolites in the bloodstream are associated with a higher risk for heart disease. This is a new source of information that can potentially be added to traditional measures such as cholesterol, BP, diabetes, smoking, etc, and help physicians more accurately predict which patients will develop heart disease.
Though this is a promising start, but there is much to be done before this new information can be used in clinical practice. The next step would be to confirm these associations between the metabolites and heart disease in other populations and make sure the associations are generalizable to different types of people around the world. If that were confirmed, then studies would need to be performed to see exactly how much the metabolite levels improve the ability to predict which patients will develop heart disease. If that looked favorable, then it would be necessary to develop a blood test that can accurately, reproducibly and affordably measure the amounts of the metabolites in the blood, so that it can be widely applied in the clinical setting.
This study shows that metabolites might represent a valuable new source of information, and we can expect that future studies will identify an even larger number of metabolites that can be readily measured and might further improve the risk prediction of heart disease.
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