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

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

doi:10.1161/circulationaha.113.002500

Cited by 451 publications

(349 citation statements)

References 41 publications

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“…In the Bruneck study, mass spectrometry demonstrated that certain species of triacylglycerols, cholesterol esters, and phosphatidylethanolamines have a strong predictive value for the development of cardiovascular disease. 65 Mass spectrometry has also shown that sphingolipids, phospholipids, cholesterol esters, and gylcerolipids are associated with an increased risk of adverse cardiovascular events in patients with diabetes mellitus. 66 High-throughput metabolite profiling by nuclear magnetic resonance spectroscopy has also identified a further 33 lipids and metabolites that are predictive of cardiovascular events, although only 4 metabolites showed independent risk of adverse cardiovascular events when routine lipids were adjusted for, phenylalanine and monounsaturated fatty acid levels were associated with increased risk whereas omega-6 fatty acids and docosahexaenoic acid were associated with decreased risk.…”

Section: Lipidsmentioning

confidence: 99%

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Thomas

Lip

2017

Circulation Research

111

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Abstract:The use of risk markers has transformed cardiovascular medicine, exemplified by the routine assessment of troponin, for both diagnosis and assessment of prognosis in patients with chest pain. Clinical risk factors form the basis for risk assessment of cardiovascular disease and the addition of biochemical, cellular, and imaging parameters offers further refinement. Identifying novel risk factors may allow greater risk stratification and a steady, but gradual progression toward precision medicine. Indeed, the generation of data in this area of research is explosive and when combined with new technologies and techniques provides the potential for more refined, targeted approaches to cardiovascular medicine. Although discussing the most recent developments in this field, this review article aims to strike a balance between novelty and validity by focusing on recent large samplesize studies that have been validated in a separate cohort in most cases. Risk markers related to atherosclerosis, thrombosis, inflammation, cardiac injury, and fibrosis are introduced in the context of their pathophysiology. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. Subsequently the prognostic ability of these risk markers in coronary artery disease, heart failure, and atrial fibrillation is discussed in detail. ( addition to these roles in the pathogenesis of coronary artery disease, lipid-related molecules have been identified to be markers of inflammation and oxidative stress (Table 1). Thrombosis-Related Risk MarkersAfter atherosclerotic plaque rupture, platelets adhere to exposed subendothelial components, such as collagen and von Willebrand factor, which promotes platelet activation and aggregation. 10 In addition, platelet activation is potentiated by exposure to released soluble agonists, such as thrombin and ADP.10 Activated platelets then further release ADP, which acts on platelet P2Y 12 ADP receptors and has a central role in amplifying the response of platelets to the initial stimulus. 10 Platelet reactivity to various agonists, including ADP, has been studied extensively in the context of acute coronary syndrome (ACS; Table 2). 11 The VerifyNow and Multiplate pointof-care tests allow for the measurement of platelet aggregation in response to stimulation, and it has been shown that high platelet reactivity is associated with adverse cardiovascular events. 26 Platelet microparticles are released on platelet activation, and their role in cardiovascular disease is an area of active investigation (Table 2). 15 Circulating microparticles are released from cells undergoing activation or apoptosis and are a type of small plasma membrane vesicle that retain defined properties from their original cell lineage. 15 Platelet activation and aggregation lead to the activation of the coagulation cascade and the formation of a stable crosslinked fibrin clot. The balance between prothrombotic factors and endogenous fibrinolysis determines whether the thrombus propagates or instead proceeds to dis...

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Section: Lipidsmentioning

confidence: 99%

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Thomas

Lip

2017

Circulation Research

111

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“…In another 413 population based study Lyso PC (18:2) was also found to be 414 inversely associated with glucose impairment and diabetes [35]. 415 These findings were also supported by another population based 416 lipidomic analysis of Bruneck study [35,36].…”

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confidence: 77%

Identification of metabolic markers in coronary artery disease using an untargeted LC-MS based metabolomic approach

Varshney

Hamid

Ghosh

et al. 2015

Journal of Proteomics

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“…As discovered by Miller et al 17 , plasma cholesterol oleate and other SOAT2 derived CE, are valuable in predicting a patient’s possibility of having acute coronary syndrome during an attack of sudden chest pain. Furthermore, SOAT2-derived cholesterol esters have recently been identified as predictors of cardiovascular disease risk in a large unbiased human lipidomic study 18 . These results suggest that our current findings have broad implications in human disease.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol Esters (CE) Derived From Hepatic Sterol O-Acyltransferase 2 (SOAT2) Are Associated With More Atherosclerosis Than CE From Intestinal SOAT2

Zhang

Sawyer

Marshall

et al. 2014

Circulation Research

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Rationale Cholesterol esters (CE), especially cholesterol oleate, generated by hepatic and intestinal sterol O-acyltransferase 2 (SOAT2) play a critical role in cholesterol homeostasis. However, it is unknown if the contribution of intestine-derived CE from SOAT2 would have similar effects in promoting atherosclerosis progression as for liver-derived CE. Objective To test whether, in low-density lipoprotein receptor null (LDLr−/−) mice, the conditional knockout of intestinal SOAT2 (SOAT2SI-/SI-) or hepatic SOAT2 (SOAT2L-/L-) would equally limit atherosclerosis development when compared to the global deletion of SOAT2 (SOAT2−/−). Methods and Results SOAT2 conditional knockout mice were bred with LDLr−/− mice creating LDLr−/− mice with each of the specific SOAT2 gene deletions. All mice then were fed an atherogenic diet for 16 weeks. SOAT2SI-/SI-LDLr−/− and SOAT2−/− LDLr−/− mice had significantly lower levels of intestinal cholesterol absorption, more fecal sterol excretion, and lower biliary cholesterol levels. Analysis of plasma LDL showed that all mice with SOAT2 gene deletions had LDL CE with reduced percentages of cholesterol palmitate and cholesterol oleate. Each of the LDLr−/− mice with SOAT2 gene deletions had lower accumulations of total cholesterol and CE in the liver compared with control mice. Finally, aortic atherosclerosis development was significantly lower in all mice with global or tissue-restricted SOAT2 gene deletions. Nevertheless, SOAT2−/− LDLr−/− and SOAT2L-/L-LDLr−/− mice had less aortic CE accumulation and smaller aortic lesions than SOAT2SI-/SI-LDLr−/− mice. Conclusions SOAT2-derived CE from both the intestine and liver significantly contribute to the development of atherosclerosis, although the CE from the hepatic enzyme appeared to promote more atherosclerosis development.

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

Cited by 451 publications

References 41 publications

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Identification of metabolic markers in coronary artery disease using an untargeted LC-MS based metabolomic approach

Cholesterol Esters (CE) Derived From Hepatic Sterol O-Acyltransferase 2 (SOAT2) Are Associated With More Atherosclerosis Than CE From Intestinal SOAT2

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