Lipidomics Profiling and Risk of Cardiovascular Disease in the Prospective Population-Based Bruneck Study

Christin Stegemann, Raimund Pechlaner, Peter Willeit, Sarah Langley, Massimo Mangino, Ursula Mayr, Cristina Menni, Alireza Moayyeri, Peter Santer, Gregorio Rungger, Tim D Spector, Johann Willeit, Stefan Kiechl, Manuel Mayr

Research output: Contribution to journalArticlepeer-review

420 Citations (Scopus)

Abstract

Background—The bulk of cardiovascular disease risk is not explained by traditional risk factors. Recent advances in mass spectrometry allow the identification and quantification of hundreds of lipid species. Molecular lipid profiling by mass spectrometry may improve cardiovascular risk prediction.

Methods and Results—Lipids were extracted from 685 plasma samples of the prospective population-based Bruneck Study (baseline evaluation in 2000). 135 lipid species from eight different lipid classes were profiled by shotgun lipidomics using a triple quadrupole mass spectrometer. Levels of individual species of cholesterol esters (CE), lysopho-phatidylcholines, phosphatidyl-cholines, phosphatidyl-ethanolamines (PE), sphingomyelins, and triacylglycerols (TAG) were associated with cardiovascular disease over a 10-year observation period (2000 to 2010, 90 incident events). Among the lipid species with the strongest predictive value were TAGs and CEs with low carbon number and double bond content, including TAG(54:2) and CE(16:1), as well as PE(36:5) (P=5.1×10-07, 2.5×10-03, 2.2×10-04, respectively). Consideration of these three lipid species on top of traditional risk factors resulted in improved risk discrimination and classification for cardiovascular disease (cross-validated Δc-index [95% confidence interval], 0.0210 [0.0010, 0.0422]; IDI, 0.0212 [0.0031, 0.0406]; continuous NRI, 0.398 [0.175, 0.619]). A similar shift in the plasma fatty acid composition was associated with cardiovascular disease in the UK Twin Registry (n=1453, 45 cases).

Conclusions—This study applied mass spectrometry-based lipidomics profiling to population-based cohorts and identified molecular lipid signatures for cardiovascular disease. Molecular lipid species constitute promising new biomarkers that outperform the conventional biochemical measurements of lipid classes currently used in the clinics.
Original languageEnglish
Pages (from-to)1821-1831
Number of pages11
JournalCirculation (Baltimore)
Volume129
Issue number18
Early online date12 Mar 2014
DOIs
Publication statusPublished - 6 May 2014

Fingerprint

Dive into the research topics of 'Lipidomics Profiling and Risk of Cardiovascular Disease in the Prospective Population-Based Bruneck Study'. Together they form a unique fingerprint.

Cite this