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Glycerophosphocholine Metabolites and Cardiovascular Disease Risk Factors in AdolescentsClinical Perspective: A Cohort Study

Published on Nov 22, 2016in Circulation 23.05
· DOI :10.1161/CIRCULATIONAHA.116.022993
Catriona Syme13
Estimated H-index: 13
Simon Czajkowski1
Estimated H-index: 1
+ 13 AuthorsZdenka Pausova41
Estimated H-index: 41
Background: Glycerophosphocholine (GPC) metabolites modulate atherosclerosis and thus risk for cardiovascular disease (CVD). Preclinical CVD may start during adolescence. Here, we used targeted serum lipidomics to identify a new panel of GPCs, and tested whether any of these GPCs are associated, in adolescence, with classical risk factors of CVD, namely excess visceral fat (VF), elevated blood pressure, insulin resistance, and atherogenic dyslipidemia. Methods: We studied a population-based sample of 990 adolescents (12–18 years, 48% male), as part of the Saguenay Youth Study. Using liquid chromatography-electrospray ionization-mass spectrometry, we identified 69 serum GPCs within the 450 to 680 m / z range. We measured VF with MRI. Results: We identified several novel GPCs that were associated with multiple CVD risk factors. Most significantly, PC16:0/2:0 was negatively associated with VF ( P =1.4×10 –19 ), blood pressure ( P =7.7×10 –5 ), and fasting triacylglycerols ( P =9.0×10 –5 ), and PC14:1/0:0 was positively associated with VF ( P =3.0×10 –7 ), fasting insulin ( P =5.4×10 –32 ), and triacylglycerols ( P =1.4×10 –29 ). The Sobel test of mediation revealed that both GPCs mediated their respective relations between VF (as a potential primary exposure) and CVD risk factors (as outcomes, P values –3 ). Furthermore, a GPC shown recently to predict incident coronary heart disease in older adults, PC18:2/0:0, was associated with several CVD risk factors in adolescents; these associations were less strong than those with the newly identified GPCs. Conclusions: We identified novel GPCs strongly associated with multiple CVD risk factors in adolescents. These GPCs may be sensitive indicators of obesity-related risk for CVD outcomes in adults, and may improve biological understanding of CVD risk.
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Published on Mar 27, 2016in International Journal of Epidemiology 7.34
Zdenka Pausova41
Estimated H-index: 41
Tomáš Paus82
Estimated H-index: 82
(MIND Institute)
+ 8 AuthorsJean R. Séguin43
Estimated H-index: 43
(UdeM: Université de Montréal)
The Saguenay Youth Study (SYS) is a two-generational study of adolescents and their parents (n = 1029 adolescents and 962 parents) aimed at investigating the aetiology, early stages and trans-generational trajectories of common cardiometabolic and brain diseases. The ultimate goal of this study is to identify effective means for increasing healthy life expectancy. The cohort was recruited from the genetic founder population of the Saguenay Lac St Jean region of Quebec, Canada. The participants u...
Published on Feb 1, 2016in The Journal of Clinical Endocrinology and Metabolism 5.61
You Cheol Hwang2
Estimated H-index: 2
(Kyung Hee University),
Wilfred Y. Fujimoto60
Estimated H-index: 60
(UW: University of Washington)
+ 3 AuthorsEdward J. Boyko74
Estimated H-index: 74
Context: Atherogenic dyslipidemia is frequently observed in persons with a greater amount of visceral adipose tissue (VAT). However, it is still uncertain whether VAT is independently associated with the future development of atherogenic dyslipidemia. Objectives: The aim of this study was to determine whether baseline and changes in VAT and subcutaneous adipose tissue (SAT) are associated with future development of atherogenic dyslipidemia independent of baseline lipid levels and standard anthro...
Published on Oct 27, 2015in Circulation 23.05
Tobin M. Abraham5
Estimated H-index: 5
(NIH: National Institutes of Health),
Alison Pedley16
Estimated H-index: 16
(Brigham and Women's Hospital)
+ 2 AuthorsCaroline S. Fox124
Estimated H-index: 124
(NIH: National Institutes of Health)
Background—Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) vary in volume and quality. We evaluated whether fat volume or attenuation (indirect measure of quality) predicts metabolic risk factor changes. Methods and Results—Framingham Heart Study Multi-detector Computed Tomography Substudy participants (n=1730, 45% women) were followed up over a mean of 6.2 years. Baseline VAT and SAT volume (in cm3) and attenuation (in Hounsfield units) were assessed. Outcomes included blood...
Published on Jan 6, 2015in Neurology 8.69
Mariona Jové24
Estimated H-index: 24
Gerard Mauri-Capdevila3
Estimated H-index: 3
+ 8 AuthorsManuel Portero-Otin48
Estimated H-index: 48
Objective: To discover, by using metabolomics, novel candidate biomarkers for stroke recurrence (SR) with a higher prediction power than present ones. Methods: Metabolomic analysis was performed by liquid chromatography coupled to mass spectrometry in plasma samples from an initial cohort of 131 TIA patients recruited Results: Metabolomics analyses could predict SR using pattern recognition methods. Low concentrations of a specific lysophosphatidylcholine (LysoPC[16:0]) were significantly associ...
Published on Dec 11, 2014in PLOS Genetics 5.22
Andrea Ganna22
Estimated H-index: 22
(KI: Karolinska Institutet),
Samira Salihovic20
Estimated H-index: 20
(Uppsala University)
+ 12 AuthorsMihkel Zilmer37
Estimated H-index: 37
(UT: University of Tartu)
Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascula...
Published on Dec 1, 2014in Circulation-cardiovascular Genetics 4.86
Helmut Hinterwirth2
Estimated H-index: 2
('KCL': King's College London),
Christin Stegemann6
Estimated H-index: 6
('KCL': King's College London),
Manuel Mayr67
Estimated H-index: 67
('KCL': King's College London)
Lipidomics is the comprehensive analysis of molecular lipid species, including their quantitation and metabolic pathways. The huge diversity of native lipids and their modifications make lipidomic analyses challenging. The method of choice for sensitive detection and quantitation of molecular lipid species is mass spectrometry, either by direct infusion (shotgun lipidomics) or coupled with liquid chromatography. Although shotgun lipidomics allows for high-throughput analysis, low-abundant lipid ...
Published on Oct 23, 2014in PLOS ONE 2.78
Susanne Heimerl14
Estimated H-index: 14
Mariellen Fischer47
Estimated H-index: 47
+ 4 AuthorsGerdSchmitz78
Estimated H-index: 78
Background Obesity and related diseases of the metabolic syndrome contribute to the major health problems in industrialized countries. Alterations in the metabolism of lipid classes and lipid species may significantly be involved in these metabolic overload diseases. However, little is known about specific lipid species in this syndrome and existing data are contradictive. Methods In this study, we quantified plasma lipid species by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in...
Published on Sep 1, 2014in Journal of Lipid Research 4.74
Gopal K. Marathe11
Estimated H-index: 11
(University of Mysore),
Chaitanya Pandit1
Estimated H-index: 1
(University of Mysore)
+ 3 AuthorsCletus Joseph Michael D’Souza1
Estimated H-index: 1
(University of Mysore)
Mounting ambiguity persists around the functional role of the plasma form of platelet-activating factor acetylhydrolase (PAF-AH). Because PAF-AH hydrolyzes PAF and related oxidized phospholipids, it is widely accepted as an anti-inflammatory enzyme. On the other hand, its actions can also generate lysophosphatidylcholine (lysoPC), a component of bioactive atherogenic oxidized LDL, thus allowing the enzyme to have proinflammatory capabilities. Presence of a canonical lysoPC receptor has been seri...
Published on May 6, 2014in Circulation 23.05
Christin Stegemann6
Estimated H-index: 6
('KCL': King's College London),
Raimund Pechlaner12
Estimated H-index: 12
+ 11 AuthorsGregor Rungger11
Estimated H-index: 11
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). One hundred thirty-five lipid species from 8 different...
Published on Jan 17, 2014in PLOS ONE 2.78
Alexander Sigruener13
Estimated H-index: 13
(University of Regensburg),
Marcus E. Kleber47
Estimated H-index: 47
(Heidelberg University)
+ 3 AuthorsWinfried März87
Estimated H-index: 87
(Medical University of Graz)
Vascular and metabolic diseases cause half of total mortality in Europe. New prognostic markers would provide a valuable tool to improve outcome. First evidence supports the usefulness of plasma lipid species as easily accessible markers for certain diseases. Here we analyzed association of plasma lipid species with mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Plasma lipid species were quantified by electrospray ionization tandem mass spectrometry and Cox proportio...
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