Metabolomics signature improves the prediction of cardiovascular events in elderly subjects

Rizza, Stefano; Copetti, Massimiliano; Rossi, Cláudia; Cianfarani, Maria Assunta; Zucchelli, Mirco; Luzi, Alessio; Pecchioli, Chiara; Porzio, Ottavia; Cola, Giovanni Di; Urbani, Andrea; Pellegrini, Fabio; Federici, Massimo

doi:10.1016/j.atherosclerosis.2013.10.029

Cited by 141 publications

(130 citation statements)

References 28 publications

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“…Recent research indicates that medium-and long-chain acylcarnitines predict cardiovascular events in elderly subjects. 22 By contrast, we did not find significant differences in serum levels of acylcarnitines between the study groups. However, Rizza et al 22 determined serum acylcarnitines by MRM, whereas we used precursor scan approach.…”

Section: Discussionmentioning

confidence: 52%

“…22 By contrast, we did not find significant differences in serum levels of acylcarnitines between the study groups. However, Rizza et al 22 determined serum acylcarnitines by MRM, whereas we used precursor scan approach. Furthermore, the mean age of the subjects in the aforementioned study was 85 years, 22 but in our study the mean age of the subjects was 66 years.…”

Section: Discussionmentioning

confidence: 52%

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Metabolomic signature of arterial stiffness in male patients with peripheral arterial disease

et al. 2015

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Arterial stiffness is an independent determinant of cardiovascular risk and a marker of subclinical organ damage. Metabolomics may facilitate identification of novel low-molecular cardiovascular risk factors. The aim of the present study was to compare metabolic signatures and functional-biochemical characteristics of patients with peripheral arterial disease (PAD) and clinically healthy subjects. We studied 42 men with symptomatic PAD (aged 66±7 years) and 46 healthy men (aged 66±8 years). Aortic pulse wave velocity (aPWV) was assessed by applanation tonometry using the Sphygmocor device. Metabolic profiling was performed with high-performance liquid chromatography and mass spectrometry. Serum oxidized low-density lipoprotein (oxLDL) level was measured by enzyme-linked immunosorbent assay. The aPWV as well as serum levels of lactate, free carnitine and 11 amino acids including tyrosine were higher among the patients with PAD. In contrast, serum levels of pyruvate, citrate, α-ketoglutarate, aconitate and cysteine were higher in the control group. In multiple regression models, aPWV was independently determined by log-tyrosine and log-oxLDL in the patients (R(2)=0.61; P<0.001) and by age, log-pyruvate and log-oxLDL in the controls (R(2)=0.52; P<0.001). Our study describes for the first time significant differences in metabolomic signature of patients with advanced atherosclerosis compared with clinically healthy controls. The aPWV is independently associated with serum levels of tyrosine and oxLDL in the patients with PAD and is related to pyruvate and oxLDL levels in the control group. The measurement of low-molecular metabolites, which are related to changes in vascular phenotypes, may lead to identification of novel vascular risk markers.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 52%

Metabolomic signature of arterial stiffness in male patients with peripheral arterial disease

et al. 2015

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“…Moreover, significantly different acylcarnitine profiles were observed among subjects with normal glucose tolerance, prediabetic states, or type 2 diabetes in a German study (22). Recently, several prospective studies indicated that medium-and/or long-chain acylcarnitines predicted cardiovascular events or mortality in people aged .85 years or selected patients undergoing cardiac catheterization or dialysis (23)(24)(25). However, previous European studies using the targeted BIOCRATES metabolomics platform failed to demonstrate a significant association between acylcarnitines and incident diabetes (26,27).…”

Section: Discussionmentioning

confidence: 95%

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

et al. 2016

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OBJECTIVEAcylcarnitines were suggested as early biomarkers even prior to insulin resistance in animal studies, but their roles in predicting type 2 diabetes were unknown. Therefore, we aimed to determine whether acylcarnitines could independently predict type 2 diabetes by using a targeted metabolic profiling approach. RESEARCH DESIGN AND METHODSA population-based prospective study was conducted among 2,103 communityliving Chinese individuals aged 50-70 years from Beijing and Shanghai with a mean follow-up duration of 6 years. Fasting glucose, glycohemoglobin, and insulin were determined at baseline and in a follow-up survey. Baseline plasma acylcarnitines were profiled by liquid chromatography-tandem mass spectrometry. RESULTSOver the 6-year period, 507 participants developed diabetes. A panel of acylcanitines, especially with long chain, was significantly associated with increased risk of type 2 diabetes. The relative risks of type 2 diabetes per SD increase of the predictive model score were 2.48 (95% CI 2.20-2.78) for the conventional and 9.41 (95% CI 7.62-11.62) for the full model including acylcarnitines, respectively. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in the full model compared with 0.73 in the conventional model. Similar associations were obtained when the predictive models were established separately among Beijing or Shanghai residents. CONCLUSIONSA panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors. These findings need to be replicated in other populations, and the underlying mechanisms should be elucidated.The escalating global epidemic of type 2 diabetes has contributed considerably to socioeconomic burdens in both developed and developing countries (1). To understand biological mechanisms and improve clinical predictions, it is essential to identify novel biomarkers to enhance the capability to predict early pathophysiological changes (2). As a largely preventable disease, early prediction is the key to control the epidemic trend of type 2 diabetes, particularly in those countries with

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“…Rizza et al [37] have hypothesized that metabolomic profiling would identify biomarkers predicting major cardiovascular events in elderly people, and they have demonstrated that age-related mitochondrial dysfunction as evaluated by metabolomic profiling is associated with major cardiovascular events independently of standard predictors. …”

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confidence: 99%

Mitochondrial Aging: Focus on Mitochondrial DNA Damage in Atherosclerosis - A Mini-Review

et al. 2014

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Atherosclerosis is a complex disease which can be described as an excessive fibrofatty, proliferative, inflammatory response to damage to the artery wall involving several cell types such as smooth muscle cells, monocyte-derived macrophages, lymphocytes, dendritic cells and platelets. On the other hand, atherosclerosis is a typical age-related degenerative pathology, which is characterized by signs of cell senescence in the arterial wall including reduced cell proliferation, irreversible growth arrest and apoptosis, increased DNA damage, the presence of epigenetic modifications, shortening of telomere length and mitochondrial dysfunction. The most prominent characteristics of mitochondrial aging are their structural alterations and mitochondrial DNA damage. The mechanisms of mitochondrial genome damage in the development of chronic age-related diseases such as atherosclerosis are not yet well understood. This review focuses on the latest findings from studies of those mutations of the mitochondrial genome which may play an important role in the development of atherosclerosis and which are, at the same time, also markers of mitochondrial aging and cell senescence.

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Metabolomics signature improves the prediction of cardiovascular events in elderly subjects

Abstract: Aging mitochondrial dysfunction evaluated by metabolomic profiling is associated with MACEs, independently of standard predictors.

Cited by 141 publications

References 28 publications

Metabolomic signature of arterial stiffness in male patients with peripheral arterial disease

Metabolomic signature of arterial stiffness in male patients with peripheral arterial disease

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

Mitochondrial Aging: Focus on Mitochondrial DNA Damage in Atherosclerosis - A Mini-Review

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