Dataset Information

Lipidomic profiling identifies signatures of metabolic risk.

ABSTRACT: BACKGROUND:Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. METHODS:We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. RESULTS:Thirty-nine lipids were associated with obesity and eight with dysglycemia in the FHS. Of 32 lipids that were available for replication for obesity and six for dyslipidemia, 28 (88%) replicated for obesity and five (83%) for dysglycemia. Four lipids were associated with longitudinal changes in body mass index and four were associated with changes in fasting blood glucose in the FHS. CONCLUSIONS:We identified and replicated several novel lipid biomarkers of key metabolic traits. The lipid moieties identified in this study are involved in biological pathways of metabolic risk and can be explored for prognostic and therapeutic utility.

SUBMITTER: Yin X

PROVIDER: S-EPMC6938899 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Lipidomic profiling identifies signatures of metabolic risk.

Yin Xiaoyan X Willinger Christine M CM Keefe Joshua J Liu Jun J Fernández-Ortiz Antonio A Ibáñez Borja B Peñalvo José J Adourian Aram A Chen George G Corella Dolores D Pamplona Reinald R Portero-Otin Manuel M Jove Mariona M Courchesne Paul P van Duijn Cornelia M CM Fuster Valentín V Ordovás José M JM Demirkan Ayşe A Larson Martin G MG Levy Daniel D

EBioMedicine 20191224

<h4>Background</h4>Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors.<h4>Methods</h4>We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external vali ...[more]

PMID: 31877415

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Project description:BACKGROUND:Plasma lipidomic measures may enable improved prediction of cardiovascular outcomes in secondary prevention. The aim of this study is to determine the association of plasma lipidomic measurements with cardiovascular events and assess their potential to predict such events. METHODS:Plasma lipids (n = 342) were measured in a retrospective subcohort (n = 5,991) of the LIPID study. Proportional hazards regression was used to identify lipids associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and cardiovascular death. Multivariable models adding lipid species to traditional risk factors were created using lipid ranking established from the Akaike information criterion within a 5-fold cross-validation framework. The results were tested on a diabetic case cohort from the ADVANCE study (n = 3,779). RESULTS:Specific ceramide species, sphingolipids, phospholipids, and neutral lipids containing omega-6 fatty acids or odd-chain fatty acids were associated with future cardiovascular events (106 species) and cardiovascular death (139 species). The addition of 7 lipid species to a base model (11 conventional risk factors) resulted in an increase in the C-statistics from 0.629 (95% CI, 0.628-0.630) to 0.654 (95% CI, 0.653-0.656) for prediction of cardiovascular events and from 0.673 (95% CI, 0.671-0.675) to 0.727 (95% CI, 0.725-0.728) for prediction of cardiovascular death. Categorical net reclassification improvements for cardiovascular events and cardiovascular death were 0.083 (95% CI, 0.081-0.086) and 0.166 (95% CI, 0.162-0.170), respectively. Evaluation on the ADVANCE case cohort demonstrated significant improvement on the base models. CONCLUSIONS:The improvement in the prediction of cardiovascular outcomes, above conventional risk factors, demonstrates the potential of plasma lipidomic profiles as biomarkers for cardiovascular risk stratification in secondary prevention. FUNDING:Bristol-Myers Squibb, the National Health and Medical Research Council of Australia (grants 211086, 358395, and 1029754), and the Operational Infrastructure Support Program of the Victorian government of Australia.

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Lipidomic profiling identifies signatures of metabolic risk.

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Lipidomic profiling identifies signatures of metabolic risk.

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