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Blood metabolomic fingerprint is distinct in healthy coronary and in stenosing or microvascular ischemic heart disease.

ABSTRACT: The endothelium is a key variable in the pathogenesis of atherosclerosis and its complications, particularly coronary artery disease (CAD). Current evidence suggests that the endothelial status can be regarded as an integrated index of individual atherogenic and anti-atherogenic properties, and that the interaction between circulating factors and the arterial wall might be critical for atherogenesis. In organism-level investigations, a functional view is provided by metabolomics, the study of the metabolic profile of small molecules. We sought to verify whether metabolomic analysis can reveal the presence of coronary microenvironment peculiarities associated with distinct manifestations of CAD.Thirty-two coronary blood samples were analyzed using 1H-NMR-based metabolomics. Samples collected from patients with evidence of myocardial ischemia formed the case group, and were further divided into the stenotic-disease (SD) group (N = 13) and absence of stenosis (microvascular disease; "Micro") group (N = 8); specimens of patients presenting no evidence of ischemic heart disease (dilated cardiomyopathy, valvular diseases) constituted the control group (N = 11).Application of an orthogonal partial least squares discriminant analysis (OPLS-DA) model to the entire dataset clearly separated the samples into 3 groups, indicating 3 distinct metabolic fingerprints. Relative to control-group members, Micro patients showed a higher content of 2-hydroxybutirate, alanine, leucine, isoleucine, and N-acetyl groups and lower levels of creatine/phosphocreatine, creatinine, and glucose, whereas SD patients showed higher levels of 3-hydroxybutirate and acetate and a lower content of 2-hydroxybutirate. Moreover, relative to SD patients, Micro patients showed higher levels of 2-hydroxybutirate, alanine, leucine, and N-acetyl groups and lower levels of 3-hydroxybutirate and acetate.Specific coronary microenvironments are likely associated with distinct development and pathological expression of CAD.

SUBMITTER: Deidda M

PROVIDER: S-EPMC5442646 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Blood metabolomic fingerprint is distinct in healthy coronary and in stenosing or microvascular ischemic heart disease.

Deidda Martino M Piras Cristina C Cadeddu Dessalvi Christian C Congia Damiana D Locci Emanuela E Ascedu Federica F De Candia Gianfranco G Cadeddu Mauro M Lai Giorgio G Pirisi Raimondo R Atzori Luigi L Mercuro Giuseppe G

Journal of translational medicine 20170523 1

<h4>Background</h4>The endothelium is a key variable in the pathogenesis of atherosclerosis and its complications, particularly coronary artery disease (CAD). Current evidence suggests that the endothelial status can be regarded as an integrated index of individual atherogenic and anti-atherogenic properties, and that the interaction between circulating factors and the arterial wall might be critical for atherogenesis. In organism-level investigations, a functional view is provided by metabolomi ...[more]

PMID: 28535803

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Project description:AimsIschaemic heart disease is the reduction of myocardial blood flow, caused by epicardial and/or microvascular disease. Both are common and prognostically important conditions, with distinct guideline-indicated management. Fractional flow reserve (FFR) is the current gold-standard assessment of epicardial coronary disease but is only a surrogate of flow and only predicts percentage flow changes. It cannot assess absolute (volumetric) flow or microvascular disease. The aim of this study was to develop and validate a novel method that predicts absolute coronary blood flow and microvascular resistance (MVR) in the catheter laboratory.Methods and resultsA computational fluid dynamics (CFD) model was used to predict absolute coronary flow (QCFD) and coronary MVR using data from routine invasive angiography and pressure-wire assessment. QCFD was validated in an in vitro flow circuit which incorporated patient-specific, three-dimensional printed coronary arteries; and then in vivo, in patients with coronary disease. In vitro, QCFD agreed closely with the experimental flow over all flow rates [bias +2.08 mL/min; 95% confidence interval (error range) -4.7 to +8.8 mL/min; R2 = 0.999, P < 0.001; variability coefficient <1%]. In vivo, QCFD and MVR were successfully computed in all 40 patients under baseline and hyperaemic conditions, from which coronary flow reserve (CFR) was also calculated. QCFD-derived CFR correlated closely with pressure-derived CFR (R2 = 0.92, P < 0.001). This novel method was significantly more accurate than Doppler-wire-derived flow both in vitro (±6.7 vs. ±34 mL/min) and in vivo (±0.9 vs. ±24.4 mmHg).ConclusionsAbsolute coronary flow and MVR can be determined alongside FFR, in absolute units, during routine catheter laboratory assessment, without the need for additional catheters, wires or drug infusions. Using this novel method, epicardial and microvascular disease can be discriminated and quantified. This comprehensive coronary physiological assessment may enable a new level of patient stratification and management.

Project description:Background The Healthy Aging Index (HAI) has been regarded as useful in capturing the health status of multiple organ systems. However, to what extent the HAI is associated with major cardiovascular events remains largely unknown. The authors constructed a modified HAI (mHAI) to quantify the association of physiological aging with major vascular events and explored how the effects of a healthy lifestyle can modify this association. Methods and Results The participants with either missing values of any individual mHAI component or major illnesses such as heart attack, angina and stroke, and self-reported cancer at baseline were excluded. The mHAI components include systolic blood pressure, reaction time, forced vital capacity, serum cystatin c, and serum glucose. The authors used Cox proportional hazard models to quantify the association of mHAI with major adverse cardiac events, major coronary events, and ischemic heart disease. Cumulative incidence at 5 and 10 years was estimated, and joint analyses were stratified by age group and 4 mHAI categories. The mHAI was significantly correlated with major cardiovascular events, which is a better reflection of the aging level of the body than chronological age. An mHAI was calculated in 338 044 participants aged 38 to 73 years in the UK Biobank. Each point increase in the mHAI was associated with a 44% higher risk of major adverse cardiac events (adjusted hazard ratio [aHR], 1.44 [95% CI, 1.40-1.49]), 44% higher risk of major coronary events (aHR, 1.44 [95% CI, 1.40-1.48]), and 36% higher risk of ischemic heart disease (aHR, 1.36 [95% CI, 1.33-1.39]). The percentage of population-attribution risk was 51% (95% CI, 47-55) for major adverse cardiac events, 49% (95% CI, 45-53) for major coronary events, and 47% (95% CI, 44-50) for ischemic heart disease, which means that a substantial portion of these events could be prevented. Systolic blood pressure was the factor most significantly associated with major adverse cardiac events (aHR, 1.94 [95% CI, 1.82-2.08]; percentage of population-attribution risk, 36%), major coronary events (aHR, 2.01 [95% CI, 1.85-2.17]; percentage of population-attribution risk, 38%), and ischemic heart disease (aHR, 1.80 [95% CI, 1.71-1.89]; percentage of population-attribution risk, 32%). A healthy lifestyle significantly attenuated mHAI associations with incidence of vascular events. Conclusions Our findings indicate that higher mHAI is associated with increased major vascular events. A healthy lifestyle may attenuate these associations.

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Blood metabolomic fingerprint is distinct in healthy coronary and in stenosing or microvascular ischemic heart disease.

Publications

Blood metabolomic fingerprint is distinct in healthy coronary and in stenosing or microvascular ischemic heart disease.

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