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Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury.

ABSTRACT: Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We applied a mass spectrometry-based metabolite profiling platform to 36 patients undergoing alcohol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned myocardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with spontaneous myocardial infarction (SMI) serving as negative and positive controls, respectively. We identified changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream contributors, and the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes after PMI in an initial derivation group and were validated in a second, independent group of PMI patients. A PMI-derived metabolic signature consisting of aconitic acid, hypoxanthine, trimethylamine N-oxide, and threonine differentiated patients with SMI from those undergoing diagnostic coronary angiography with high accuracy, and coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes. Our results identify a role for metabolic profiling in the early detection of myocardial injury and suggest that similar approaches may be used for detection or prediction of other disease states.

SUBMITTER: Lewis GD

PROVIDER: S-EPMC2525696 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury.

Lewis Gregory D GD Wei Ru R Liu Emerson E Yang Elaine E Shi Xu X Martinovic Maryann M Farrell Laurie L Asnani Aarti A Cyrille Marcoli M Ramanathan Arvind A Shaham Oded O Berriz Gabriel G Lowry Patricia A PA Palacios Igor F IF Taşan Murat M Roth Frederick P FP Min Jiangyong J Baumgartner Christian C Keshishian Hasmik H Addona Terri T Mootha Vamsi K VK Rosenzweig Anthony A Carr Steven A SA Fifer Michael A MA Sabatine Marc S MS Gerszten Robert E RE

The Journal of clinical investigation 20081001 10

Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We applied a mass spectrometry-based metabolite profiling platform to 36 patients undergoing alcohol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned myocardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with ...[more]

PMID: 18769631

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Project description:BackgroundTraditional biomarkers used to measure risk of myocardial infarction (MI) only explain a modest proportion of the incidence. Lipoprotein subfractions have the potential to improve risk prediction of MI.AimWe aimed to identify lipoprotein subfractions that were associated with imminent MI risk.MethodsWe identified apparently healthy participants with a predicted low 10-year risk of MI from The Trøndelag Health Survey 3 (HUNT3) that developed MI within 5 years after inclusion (cases, n = 50) and 100 matched controls. Lipoprotein subfractions were analyzed in serum by nuclear magnetic resonance spectroscopy at time of inclusion in HUNT3. Lipoprotein subfractions were compared between cases and controls in the full population (N = 150), and in subgroups of males (n = 90) and females (n = 60). In addition, a sub analysis was performed in participants that experienced MI within two years and their matched controls (n = 56).ResultsNone of the lipoprotein subfractions were significantly associated with future MI when adjusting for multiple testing (p<0.002). At nominal significance level (p<0.05), the concentration of apolipoprotein A1 in the smallest high-density lipoprotein (HDL) subfractions was higher in cases compared to controls. Further, in sub analyses based on sex, male cases had lower lipid concentration within the large HDL subfractions and higher lipid concentration within the small HDL subfractions compared to male controls (p<0.05). No differences were found in lipoprotein subfractions between female cases and controls. In sub analysis of individuals suffering from MI within two years, triglycerides in low-density lipoprotein were higher among cases (p<0.05).ConclusionNone of the investigated lipoprotein subfractions were associated with future MI after adjustment for multiple testing. However, our findings suggests that HDL subfractions may be of interest in relation to risk prediction for MI, especially in males. This need to be further investigated in future studies.

Project description:BackgroundAmong older adults (age ≥75 years) hospitalized for acute myocardial infarction, acute kidney injury after coronary angiography is common. Aging-related conditions may independently predict acute kidney injury, but have not yet been analyzed in large acute myocardial infarction cohorts.MethodsWe analyzed data from 2212 participants age ≥75 years in the Comprehensive Evaluation of Risk Factors in Older Patients with Acute Myocardial Infarction (SILVER-AMI) study who underwent coronary angiography. Acute kidney injury was defined using Kidney Disease Improving Global Outcomes (KDIGO) criteria (serum Cr increase ≥0.3 mg/dL from baseline or ≥1.5 times baseline). We analyzed the associations of traditional acute kidney injury risk factors and aging-related conditions (activities of daily living impairment, prior falls, cachexia, low physical activity) with acute kidney injury, and then performed logistic regression to identify independent predictors.ResultsParticipants' mean age was 81.3 years, 45.2% were female, and 9.5% were nonwhite; 421 (19.0%) experienced acute kidney injury. Comorbid diseases and aging-related conditions were both more common among individuals experiencing acute kidney injury. However, after multivariable adjustment, no aging-related conditions were retained. There were 11 risk factors in the final model; the strongest were heart failure on presentation (odds ratio [OR] 1.91; 95% confidence interval [CI], 1.41-2.59), body mass index [BMI] >30 (vs BMI 18-25: OR 1.75; 95% CI, 1.27-2.42), and nonwhite race (OR 1.65; 95% CI, 1.16-2.33). The final model achieved an area under the receiver operating characteristic curve of 0.72 and was well calibrated (Hosmer-Lemeshow P = .50). Acute kidney injury was independently associated with 6-month mortality (OR 1.98; 95% CI, 1.36-2.88) but not readmission (OR 1.26; 95% CI, 0.98-1.61).ConclusionsAcute kidney injury is common among older adults with acute myocardial infarction undergoing coronary angiography. Predictors largely mirrored those in previous studies of younger individuals, which suggests that geriatric conditions mediate their influence through other risk factors.

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Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury.

Publications

Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury.

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