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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 |

REPOSITORIES: biostudies-literature

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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.

Project description:BackgroundEmerging proteomic technologies using novel affinity-based reagents allow for efficient multiplexing with high-sample throughput. To identify early biomarkers of myocardial injury, we recently applied an aptamer-based proteomic profiling platform that measures 1129 proteins to samples from patients undergoing septal alcohol ablation for hypertrophic cardiomyopathy, a human model of planned myocardial injury. Here, we examined the scalability of this approach using a markedly expanded platform to study a far broader range of human proteins in the context of myocardial injury.MethodsWe applied a highly multiplexed, expanded proteomic technique that uses single-stranded DNA aptamers to assay 4783 human proteins (4137 distinct human gene targets) to derivation and validation cohorts of planned myocardial injury, individuals with spontaneous myocardial infarction, and at-risk controls.ResultsWe found 376 target proteins that significantly changed in the blood after planned myocardial injury in a derivation cohort (n=20; P<1.05E-05, 1-way repeated measures analysis of variance, Bonferroni threshold). Two hundred forty-seven of these proteins were validated in an independent planned myocardial injury cohort (n=15; P<1.33E-04, 1-way repeated measures analysis of variance); >90% were directionally consistent and reached nominal significance in the validation cohort. Among the validated proteins that were increased within 1 hour after planned myocardial injury, 29 were also elevated in patients with spontaneous myocardial infarction (n=63; P<6.17E-04). Many of the novel markers identified in our study are intracellular proteins not previously identified in the peripheral circulation or have functional roles relevant to myocardial injury. For example, the cardiac LIM protein, cysteine- and glycine-rich protein 3, is thought to mediate cardiac mechanotransduction and stress responses, whereas the mitochondrial ATP synthase F0 subunit component is a vasoactive peptide on its release from cells. Last, we performed aptamer-affinity enrichment coupled with mass spectrometry to technically verify aptamer specificity for a subset of the new biomarkers.ConclusionsOur results demonstrate the feasibility of large-scale aptamer multiplexing at a level that has not previously been reported and with sample throughput that greatly exceeds other existing proteomic methods. The expanded aptamer-based proteomic platform provides a unique opportunity for biomarker and pathway discovery after myocardial injury.

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

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