Metabonomics Analysis of Plasma Reveals the Lactate to Cholesterol Ratio as an Independent Prognostic Factor of Short-Term Mortality in Acute Heart Failure

PLOS ONE, Dec 2019

Objective Mortality in heart failure (AHF) remains high, especially during the first days of hospitalization. New prognostic biomarkers may help to optimize treatment. The aim of the study was to determine metabolites that have a high prognostic value. Methods We conducted a prospective study on a training cohort of AHF patients (n = 126) admitted in the cardiac intensive care unit and assessed survival at 30 days. Venous plasmas collected at admission were used for 1H NMR–based metabonomics analysis. Differences between plasma metabolite profiles allow determination of discriminating metabolites. A cohort of AHF patients was subsequently constituted (n = 74) to validate the findings. Results Lactate and cholesterol were the major discriminating metabolites predicting 30-day mortality. Mortality was increased in patients with high lactate and low total cholesterol concentrations at admission. Accuracies of lactate, cholesterol concentration and lactate to cholesterol (Lact/Chol) ratio to predict 30-day mortality were evaluated using ROC analysis. The Lact/Chol ratio provided the best accuracy with an AUC of 0.82 (P < 0.0001). The acute physiology and chronic health evaluation (APACHE) II scoring system provided an AUC of 0.76 for predicting 30-day mortality. APACHE II score, Cardiogenic shock (CS) state and Lact/Chol ratio ≥ 0.4 (cutoff value with 82% sensitivity and 64% specificity) were significant independent predictors of 30-day mortality with hazard ratios (HR) of 1.11, 4.77 and 3.59, respectively. In CS patients, the HR of 30-day mortality risk for plasma Lact/Chol ratio ≥ 0.4 was 3.26 compared to a Lact/Chol ratio of < 0.4 (P  =  0.018). The predictive power of the Lact/Chol ratio for 30-day mortality outcome was confirmed with the independent validation cohort. Conclusion This study identifies the plasma Lact/Chol ratio as a useful objective and simple parameter to evaluate short term prognostic and could be integrated into quantitative guidance for decision making in heart failure care.

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Metabonomics Analysis of Plasma Reveals the Lactate to Cholesterol Ratio as an Independent Prognostic Factor of Short-Term Mortality in Acute Heart Failure

et al. (2013) Metabonomics Analysis of Plasma Reveals the Lactate to Cholesterol Ratio as an Independent Prognostic Factor of Short-Term Mortality in Acute Heart Failure. PLoS ONE 8(4): e60737. doi:10.1371/journal.pone.0060737 Metabonomics Analysis of Plasma Reveals the Lactate to Cholesterol Ratio as an Independent Prognostic Factor of Short-Term Mortality in Acute Heart Failure Franck Desmoulin 0 Michel Galinier 0 Charlotte Trouillet 0 Matthieu Berry 0 Cle ment Delmas 0 Annie Turkieh 0 Pierre Massabuau 0 Heinrich Taegtmeyer 0 Fatima Smih 0 Philippe Rouet 0 Antonio Abbate, Virginia Commonwealth University, United States Of America 0 1 INSERM I2MC, UMR 1048, Universite UPS, Equipe Obe site et insuffisance cardiaque: approches mole culaires et cliniques , Toulouse, France, 2 CHU de Rangueil , Service de Cardiologie A, Toulouse, France, 3 Division of Cardiology, Department of Internal Medicine, The University of Texas Medical School at Houston , Houston, Texas , United States of America Objective: Mortality in heart failure (AHF) remains high, especially during the first days of hospitalization. New prognostic biomarkers may help to optimize treatment. The aim of the study was to determine metabolites that have a high prognostic value. Methods: We conducted a prospective study on a training cohort of AHF patients (n = 126) admitted in the cardiac intensive care unit and assessed survival at 30 days. Venous plasmas collected at admission were used for 1H NMR-based metabonomics analysis. Differences between plasma metabolite profiles allow determination of discriminating metabolites. A cohort of AHF patients was subsequently constituted (n = 74) to validate the findings. Results: Lactate and cholesterol were the major discriminating metabolites predicting 30-day mortality. Mortality was increased in patients with high lactate and low total cholesterol concentrations at admission. Accuracies of lactate, cholesterol concentration and lactate to cholesterol (Lact/Chol) ratio to predict 30-day mortality were evaluated using ROC analysis. The Lact/Chol ratio provided the best accuracy with an AUC of 0.82 (P , 0.0001). The acute physiology and chronic health evaluation (APACHE) II scoring system provided an AUC of 0.76 for predicting 30-day mortality. APACHE II score, Cardiogenic shock (CS) state and Lact/Chol ratio $ 0.4 (cutoff value with 82% sensitivity and 64% specificity) were significant independent predictors of 30-day mortality with hazard ratios (HR) of 1.11, 4.77 and 3.59, respectively. In CS patients, the HR of 30-day mortality risk for plasma Lact/Chol ratio $ 0.4 was 3.26 compared to a Lact/Chol ratio of , 0.4 (P = 0.018). The predictive power of the Lact/Chol ratio for 30-day mortality outcome was confirmed with the independent validation cohort. Conclusion: This study identifies the plasma Lact/Chol ratio as a useful objective and simple parameter to evaluate short term prognostic and could be integrated into quantitative guidance for decision making in heart failure care. - Acute heart failure (AHF) is the most frequent cause of hospital admission among patients over 65 years [1] and a common presentation of patients admitted to an intensive care unit. Despite advances in treatment, morbidity and mortality of AHF remain high [2] as it is the case with the rate of rehospitalizations [3]. A survey on the quality of care among patients with heart failure in Europe has shown 13.5% mortality between admission and 12 weeks follow-up [4]. There is a need for a simple test to identify patients with the higher mortality risk in order to optimize medical care. Evaluation of heart failure patients includes a focused history, physical examination, an electrocardiogram and an echocardiogram. Altogether, these complementary approaches are aimed at better management strategies. Measurements of the biomarker brain natriuretic peptides (BNPs) are the most commonly used HF biomarkers associated with altered hemodynamics [5]. BNPs are of both diagnostic and prognostic importance, and BNP levels at admission are significantly higher in patients who suffered a cardiac death within 3 months of hospital discharge [6]. However, blood BNPs level monitoring has limitations. Several reports have underlined their high variability despite some improvement gained with the quantification of amino-terminal pro-BNP [6,7]. Recently, positive serum cardiac troponin I was associated with high inhospital mortality [8], reflecting heart muscle damage. However, the quest for prognostic biomarkers is an ongoing challenge because so far no blood molecule has been identified as a marker with a significantly high level of specificity and sensibility. For the last decade the omics technology has gained in popularity in screens of gene expression, proteins and metabolites [9,10,11,12,13]. The level of severity of heart disease affects the blood metabonome [14,15]. We hypothesized that the plasma metabolome may be a predictor of short-t (...truncated)


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Franck Desmoulin, Michel Galinier, Charlotte Trouillet, Matthieu Berry, Clément Delmas, Annie Turkieh, Pierre Massabuau, Heinrich Taegtmeyer, Fatima Smih, Philippe Rouet. Metabonomics Analysis of Plasma Reveals the Lactate to Cholesterol Ratio as an Independent Prognostic Factor of Short-Term Mortality in Acute Heart Failure, PLOS ONE, 2013, Volume 8, Issue 4, DOI: 10.1371/journal.pone.0060737