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Oral Abstract PresentationsSession Title: Concurrent Session II D - Clinical Lipidology: Clinical Aspects of Diabetes, Obesity and Insulin Resistance

Abstract 37: Metabolomic Signatures of Metabolic Risk Factors for Atherosclerotic Cardiovascular Disease

Xiaoyan Yin, Shih-Jen Hwang, Aram Adourian, Paul Courchesne, Neal Gordon, Caroline Fox, Christopher J O’Donnell, Subha Subramanian, Peter Juhasz, Pieter Muntendam, Martin G Larson, Daniel Levy
Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:A37
Xiaoyan Yin
Boston Univ/Framingham Heart Study, Framingham, MA
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Shih-Jen Hwang
Cntr for Population Studies, NHLBI/Framingham Heart Study, Framingham, MA
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Aram Adourian
BG Medicine, Waltham, MA
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Paul Courchesne
Cntr for Population Studies, NHLBI/Framingham Heart Study, Framingham, MA
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Neal Gordon
BG Medicine, Waltham, MA
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Caroline Fox
Cntr for Population Studies, NHLBI/Framingham Heart Study, Framingham, MA
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Christopher J O’Donnell
Cntr for Cardiovascular Genomics, NHLBI/Framingham Heart Study, Framingham, MA
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Subha Subramanian
Cntr for Population Studies, NHLBI/Framingham Heart Study, Framingham, MA
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Peter Juhasz
BG Medicine, Waltham, MA
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Pieter Muntendam
BG Medicine, Waltham, MA
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Martin G Larson
Dept of Mathematics, Boston Univ/Framingham Heart Study, Framingham, MA
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Daniel Levy
Cntr for Population Studies, NHLBI/Framingham Heart Study, Framingham, MA
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Abstract

Background: Multiple cardiovascular disease (CVD) risk factors cluster in the same individuals and their concurrence is used to diagnose metabolic syndrome (MetSyn), which carries substantial risk for CVD. We hypothesized that MetSyn is associated with multiple metabolomic derangements.

Methods: As part of the SABRe CVD initiative, a multi-project investigation of biomarkers of CVD and its risk factors, we designed a 2x2x2 factorial study of MetSyn risk factors that included 650 individuals from the Framingham Heart Study (out of a total N of ∼3200) assigned to 8 unique groups of approximately 81 individuals each, sampled from high vs. low strata of BMI, lipids, and glucose. We conducted gas chromatography-mass spectroscopy (GC/MS) on plasma samples from 650 eligible individuals. General linear modeling was used to identify biomarkers that differed across all 8 groups or differed in their main effects on individual risk factors.

Results: Characteristics of the study sample (mean±SD), according to group assignment, are presented in the Table. GC/MS characterized 149 metabolites; of these 18 differed across all groups at P<5x10-8 and 36 differed at P<0.00001. The top 3 most highly significant metabolites across all groups were glucose (P=2x10-40), glutamic acid (P=4x10-26), and sphingomyelins (lowest P=8x10-25). The top 3 most highly significant main effects of metabolites for BMI were: glutamic acid (P=2x10-18), sitosterol (P=2x10-10), and uric acid (P=3x10-10), for dyslipidemia: sphingomyelins (lowest P=1x10-27), glutamic acid (P=5x10-20), and lactic acid (P=7x10-12), and for dysglycemia: glucose (P=1x10-42), fructose (P=3x10-7), and 2-hydroxybutanoic acid (P=6x10-7).

Conclusions: Metabolomic profiling identified multiple biomarker signatures of MetSyn and its major metabolic risk factors. These novel findings warrant external replication. Understanding the pathways represented by our results may help to unravel the molecular derangements contributing to MetSyn and its constituent risk factors. This knowledge may identify therapeutic targets for the prevention and treatment of CVD.

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  • metabolomics
  • metabolic risk factors
  • metabolic syndrome
  • © 2012 by American Heart Association, Inc.
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    Abstract 37: Metabolomic Signatures of Metabolic Risk Factors for Atherosclerotic Cardiovascular Disease
    Xiaoyan Yin, Shih-Jen Hwang, Aram Adourian, Paul Courchesne, Neal Gordon, Caroline Fox, Christopher J O’Donnell, Subha Subramanian, Peter Juhasz, Pieter Muntendam, Martin G Larson and Daniel Levy
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:A37, originally published October 20, 2015

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    Abstract 37: Metabolomic Signatures of Metabolic Risk Factors for Atherosclerotic Cardiovascular Disease
    Xiaoyan Yin, Shih-Jen Hwang, Aram Adourian, Paul Courchesne, Neal Gordon, Caroline Fox, Christopher J O’Donnell, Subha Subramanian, Peter Juhasz, Pieter Muntendam, Martin G Larson and Daniel Levy
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:A37, originally published October 20, 2015
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