Large-scale plasma lipidomic profiling identifies lipids that predict cardiovascular events in secondary prevention

Mundra, Piyushkumar A.; Barlow, Christopher K.; Nestel, Paul J.; Barnes, Elizabeth H; Kirby, Adrienne; Thompson, Peter L.; Sullivan, David; Alshehry, Zahir H.; Mellett, Natalie A.; Huynh, Kevin; Jayawardana, Kaushala S.; Giles, Corey; McConville, Malcolm J.; Zoungas, Sophia; Hillis, Graham S.; Chalmers, John; Woodward, Mark; Wong, Gerard; Kingwell, Bronwyn A.; Simes, John; Tonkin, Andrew; Meikle, Peter J.; Investigators, Lipid Study

doi:10.1172/jci.insight.121326

Cited by 112 publications

(82 citation statements)

References 37 publications

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“…The findings were first documented in the LURIC study [23] and replicated in the ATHEROREMO-IVUS study [28,29]. FINRISK 2002 study, Corogene study, PREDIMED trial, ADVANCE study, and LIPID study consistently confirmed the findings [24,26,[30][31][32].…”

Section: Yesmentioning

confidence: 68%

“…The findings were observed in the LURIC study, WHI, PREDIMED trial, ADVANCE trial, and LIPID study [23,24,26,[32][33][34], and the associations persisted after adjusting for HDL-c and LDL-c.…”

Section: Yesmentioning

confidence: 74%

“…As to methods of lipid measurement, two early studies used shotgun lipidomics [19,20], two studies used NMR measuring total lipids, triglycerides, and cholesterol within l4 lipoprotein subclasses [21,22], and the majority of studies used LC-MS, measuring hundreds of lipids [16][17][18][19][20][21][22][23][24][25][26][27]. Eight of the 16 studies were lipidomics/metabolomics-wide association studies that assessed associations of all measured lipids with CVD outcomes [19][20][21][22][23][24][25][26], six studies used a candidate-lipid approach by focusing on specific lipids such as ceramides [27][28][29][30][31][32], and two studies classified lipids into groups and examined global associations of lipid species with CVD outcomes [33,34]. Of the 16 studies, 6 studies included participants with a history of coronary heart disease (CHD) and focused on secondary prevention [23,24,26,28,29,31], and 10 studies focused on primary prevention of CVD [19][20][21][22]25,…”

Section: Summary Of Recent Studies On Lipidomics For Cvdmentioning

confidence: 99%

“…Eight of the 16 studies were lipidomics/metabolomics-wide association studies that assessed associations of all measured lipids with CVD outcomes [19][20][21][22][23][24][25][26], six studies used a candidate-lipid approach by focusing on specific lipids such as ceramides [27][28][29][30][31][32], and two studies classified lipids into groups and examined global associations of lipid species with CVD outcomes [33,34]. Of the 16 studies, 6 studies included participants with a history of coronary heart disease (CHD) and focused on secondary prevention [23,24,26,28,29,31], and 10 studies focused on primary prevention of CVD [19][20][21][22]25,27,30,[32][33][34]. Most of the included studies adjusted for lipid biomarkers such as total cholesterol and HDL-c as covariates in the model.…”

Section: Summary Of Recent Studies On Lipidomics For Cvdmentioning

confidence: 99%

“…Thereafter, the FINRISK 2002 study [30], the Corogene study [31], and the PREDIMED trial [32] specifically focused on the four mentioned ceramides and consistently found that Cer (d18:1/16:0), Cer (d18:1/18:0), and Cer (d18:1/24:1) were positively associated with CVD outcomes. Moreover, the ADVANCE and LIPID trials conducted lipidomic-wide association studies and found that, out of 300 lipids, glucosylceramides (d18:1/16:0, d18:1/18:0, and d18:1/24:1) had a strong positive association with recurrent CVD and CVD mortality [24,26]. Table 1.…”

Section: Summary Of Recent Studies On Lipidomics For Cvdmentioning

confidence: 99%

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A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins

Ding

Rexrode

2020

Metabolites

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Cutting-edge lipidomic profiling measures hundreds or even thousands of lipids in plasma and is increasingly used to investigate mechanisms of cardiovascular disease (CVD). In this review, we introduce lipidomic techniques, describe distributions of lipids across lipoproteins, and summarize findings on the association of lipids with CVD based on lipidomics. The main findings of 16 cohort studies were that, independent of total and high-density lipoprotein cholesterol (HDL-c), ceramides (d18:1/16:0, d18:1/18:0, and d18:1/24:1) and phosphatidylcholines (PCs) containing saturated and monounsaturated fatty acyl chains are positively associated with risks of CVD outcomes, while PCs containing polyunsaturated fatty acyl chains (PUFA) are inversely associated with risks of CVD outcomes. Lysophosphatidylcholines (LPCs) may be positively associated with risks of CVD outcomes. Interestingly, the distributions of the identified lipids vary across lipoproteins: LPCs are primarily contained in HDLs, ceramides are mainly contained in low-density lipoproteins (LDLs), and PCs are distributed in both HDLs and LDLs. Thus, the potential mechanism behind previous findings may be related to the effect of the identified lipids on the biological functions of HDLs and LDLs. Only eight studies on the lipidomics of HDL and non-HDL particles and CVD outcomes have been conducted, which showed that higher triglycerides (TAGs), lower PUFA, lower phospholipids, and lower sphingomyelin content in HDLs might be associated with a higher risk of coronary heart disease (CHD). However, the generalizability of these studies is a major concern, given that they used case-control or cross-sectional designs in hospital settings, included a very small number of participants, and did not correct for multiple testing or adjust for blood lipids such as HDL-c, low-density lipoprotein cholesterol (LDL-c), or TAGs. Overall, findings from the literature highlight the importance of research on lipidomics of lipoproteins to enhance our understanding of the mechanism of the association between the identified lipids and the risk of CVD and allow the identification of novel lipid biomarkers in HDLs and LDLs, independent of HDL-c and LDL-c. Lipidomic techniques show the feasibility of this exciting research direction, and the lack of high-quality epidemiological studies warrants well-designed prospective cohort studies.

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Section: Yesmentioning

confidence: 68%

Section: Yesmentioning

confidence: 74%

Section: Summary Of Recent Studies On Lipidomics For Cvdmentioning

confidence: 99%

Section: Summary Of Recent Studies On Lipidomics For Cvdmentioning

confidence: 99%

Section: Summary Of Recent Studies On Lipidomics For Cvdmentioning

confidence: 99%

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A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins

Ding

Rexrode

2020

Metabolites

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Insights into the prognosis of lipidomic dysregulation for death risk in patients with coronary artery disease

Qin

Zhu

Lai

et al. 2020

Clinical & Translational Med

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Background: Dyslipidaemia contributes to the progression of coronary artery disease (CAD) toward adverse outcomes. Plasma lipidomic measure may improve the prognostic performances of clinical endpoints of CAD. Our research is designed to identify the correlations between plasma lipid species and the risks of death, major adverse cardiovascular event (MACE) and left ventricular (LV) remodeling in patients with CAD. Methods: A total of 1569 Chinese patients with CAD, 1011 single-centre patients as internal training cohort, and 558 multicentre patients as external validation cohort, were enrolled. The concentration of plasma lipids in both cohorts was determined through widely targeted lipidomic profiling. Least absolute shrinkage and selection operator Cox and multivariate Cox regressions were used to develop prognostic models for death and MACE, respectively. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Tools for Assessing Lipoprotein Metabolism in Diabetes Mellitus

Klein

Semler

Jenkins

2023

Contemporary Diabetes

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Large-scale plasma lipidomic profiling identifies lipids that predict cardiovascular events in secondary prevention

Abstract: 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.

Cited by 112 publications

References 37 publications

A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins

A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins

Insights into the prognosis of lipidomic dysregulation for death risk in patients with coronary artery disease

Tools for Assessing Lipoprotein Metabolism in Diabetes Mellitus

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