Summary of prospective epidemiological studies examining associations between metabolites and CVD
| Reference | Study design | Cases (N) | Metabolomics platform | Main results |
| Ganna et al 9 | Prospective multicohort: TwinGene, ULSAM and PIVUS | 131 CHD events in discovery, 282 events in replication | LC-MS untargeted approach | LPC 18:1, LPC 18:2, sphingomyelin 28:1 and MG 18:2 associated with CHD MG 18:2 showed weak evidence for a causal effect on CHD risk using Mendelian randomisation analysis |
| Stegemann et al 27 | Prospective cohort study: Bruneck study | 90 CVD events | LC-MS shotgun lipidomics, 135 lipid species | Individual species of cholesterol esters, LPCs, phosphatidylcholines, phosphatidylethanolamines, sphingomyelins and triacylglycerols were associated with CVD. Small improvement in discrimination over standard CVD risk factors for disease prediction |
| Würtz et al 30 | Prospective multicohort: FINRISK study, SABRE study and British Women’s Health and Heart Study | 800 CVD events in discovery, 573 and 368 events in replication | NMR and targeted LC-MS with Metabolon 68 NMR metabolites | Phenylalanine, monounsaturated fatty acids, omega-6 fatty acids, and docosahexaenoic acids were associated with CVD events Minimal improvement in discrimination over standard CVD risk factors for disease prediction |
| Ward-Caviness et al 8 | Prospective multicohort: KORA S4, KORA S2 and AGES-REFINE | n=67, 112, 87 myocardial infarction cases, respectively | Targeted Biocrates AbsoluteIDQ p150 Kit LC -MS 188 metabolites | Arginine and LPC (LPC 17:0 and LPC 18:2) associated with myocardial infarction Metabolites increased the predictive value of the Framingham Risk Score in KORA S4 (from 0.70 to 0.78). |
| Holmes et al 29 | Nested case–control study: China Kadoorie Biobank | 912 myocardial infarctions, 1146 ischaemic strokes, 1138 intracerebral haemorrhage | NMR 225 metabolites | Triglycerides within all lipoproteins showed similar associations with myocardial infarction and ischaemic stroke, but not with intracerebral haemorrhage. Glycoprotein acetyls, ketone bodies, glucose and docosahexaenoic acid were associated with all three diseases. |
| Lind et al 22 | Prospective multicohort: TwinGene, ULSAM and PIVUS | 177 cases stroke events in discovery, 194 stroke events in replication | LC-MS untargeted approach | Sphingomyelin 32:1 was associated with incident stroke. |
| Tzoulaki et al 5 | Cross-sectional and prospective multicohort: MESA, Rotterdam Study and LOLIPOP | 630 CVD events | Untargeted NMR | 25 metabolites of atherosclerosis also associated with CVD, associations attenuated after adjustments for risk factors |
AGES-REFINE, Age, Gene/Environment Susceptibility (AGES) and the Risk Evaluation For Infarct Estimates (REFINE)-Reykjavik studies; CHD, coronary heart disease; CVD, cardiovascular disease; FINRISK, Finland Cardiovascular Risk Study; KORA, Collaborative Health Research in the Region of Augsburg; LC-MS, liquid chromatography–mass spectrometry; LOLIPOP, London Life Sciences Prospective Population Study; LPC, lysophosphatidylcholines; MESA, Multi-Ethnic Study of Atherosclerosis; MG, monoglyceride; NMR, nuclear magnetic resonance; PIVUS, Prospective Investigation of the Vasculature in Uppsala Seniors; SABRE, Southall And Brent Revisited Study; ULSAM, Uppsala Longitudinal Study of Adult Men.