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ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with hazard ratios ranging from 1.09 to 1.13.
Data source: More than 10,000 subjects in the BiomarCaRE consortium.
Disclosures: BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.