Georges Gilson

Use of Circulating MicroRNAs to Diagnose Acute Myocardial Infarction

BACKGROUND Rapid and correct diagnosis of acute myocardial infarction (MI) has an important impact on patient treatment and prognosis. We compared the diagnostic performance of high-sensitivity cardiac troponin T (hs-cTnT) and cardiac enriched microRNAs (miRNAs) in patients with MI. METHODS Circulating concentrations of cardiac-enriched miR-208b and miR-499 were measured by quantitative PCR in a case-control study of 510 MI patients referred for primary mechanical reperfusion and 87 healthy controls. RESULTS miRNA-208b and miR-499 were highly increased in MI patients (>10(5)-fold, P < 0.001) and nearly undetectable in healthy controls. Patients with ST-elevation MI (n= 397) had higher miRNA concentrations than patients with non-ST-elevation MI (n = 113) (P < 0.001). Both miRNAs correlated with peak concentrations of creatine kinase and cTnT (P < 10(-9)). miRNAs and hs-cTnT were already detectable in the plasma 1 h after onset of chest pain. In patients who presented <3 h after onset of pain, miR-499 was positive in 93% of patients and hs-cTnT in 88% of patients (P= 0.78). Overall, miR-499 and hs-cTnT provided comparable diagnostic value with areas under the ROC curves of 0.97. The reclassification index of miR-499 to a clinical model including several risk factors and hs-cTnT was not significant (P = 0.15). CONCLUSION Circulating miRNAs are powerful markers of acute MI. Their usefulness in the establishment of a rapid and accurate diagnosis of acute MI remains to be determined in unselected populations of patients with acute chest pain.

Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome After Out-of-Hospital Cardiac Arrest and Targeted Temperature Management at 33°C and 36°C

BACKGROUND Neuron-specific enolase (NSE) is a widely-used biomarker for prognostication of neurological outcome after cardiac arrest, but the relevance of recommended cutoff values has been questioned due to the lack of a standardized methodology and uncertainties over the influence of temperature management. OBJECTIVES This study investigated the role of NSE as a prognostic marker of outcome after out-of-hospital cardiac arrest (OHCA) in a contemporary setting. METHODS A total of 686 patients hospitalized after OHCA were randomized to targeted temperature management at either 33°C or 36°C. NSE levels were assessed in blood samples obtained 24, 48, and 72 h after return of spontaneous circulation. The primary outcome was neurological outcome at 6 months using the cerebral performance category score. RESULTS NSE was a robust predictor of neurological outcome in a baseline variable-adjusted model, and target temperature did not significantly affect NSE values. Median NSE values were 18 ng/ml versus 35 ng/ml, 15 ng/ml versus 61 ng/ml, and 12 ng/ml versus 54 ng/ml for good versus poor outcome at 24, 48, and 72 h, respectively (p < 0.001). At 48 and 72 h, NSE predicted neurological outcome with areas under the receiver-operating curve of 0.85 and 0.86, respectively. High NSE cutoff values with false positive rates ≤5% and tight 95% confidence intervals were able to reliably predict outcome. CONCLUSIONS High, serial NSE values are strong predictors of poor outcome after OHCA. Targeted temperature management at 33°C or 36°C does not significantly affect NSE levels. (Target Temperature Management After Cardiac Arrest [TTM]; NCT01020916).

Modeling Serum Level of S100β and Bispectral Index to Predict Outcome After Cardiac Arrest

OBJECTIVES This study was designed to evaluate multimodal prognostication in patients after cardiac arrest (CA). BACKGROUND Accurate methods to predict outcome after CA are lacking. METHODS Seventy-five patients with CA treated with therapeutic hypothermia after cardiac resuscitation were enrolled in this prospective observational study. Serum levels of neuron-specific enolase (NSE) and neuron-enriched S100 beta (S100β) were measured 48 h after CA. Bispectral index (BIS) was continuously monitored during the first 48 h after CA. The primary endpoint was neurological outcome, as defined by the cerebral performance category (CPC) at 6-month follow-up: scores 1 or 2 indicated good outcome, and scores 3 to 5, poor outcome. The secondary endpoint was survival. RESULTS A total of 46 (61%) patients survived at 6 months and 41 (55%) patients had CPC 1 or 2. Levels of NSE and S100β were higher in patients with poor outcomes compared with patients with good outcomes (4-fold and 10-fold, respectively; p < 0.001). BIS was lower in patients with poor outcomes (10-fold; p < 0.001). NSE, S100β, or BIS alone predicted neurological outcome, with areas under the receiver-operating characteristic curve (AUC) above 0.80. Combined determination of S100β and BIS had an incremental predictive value (AUC: 0.95). S100β improved discriminations based on BIS (p = 0.0008), and BIS improved discriminations based on S100β (p < 10(-5)). Patients with S100β level above 0.03 μg/l and BIS below 5.5 had a 3.6-fold higher risk of poor neurological outcome (p < 0.0001). S100β and BIS predicted 6-month mortality (log-rank statistic: 50.41; p < 0.001). CONCLUSIONS Combined determination of serum level of S100β and BIS monitoring accurately predicts outcome after CA.

Proteomic analysis of plasma samples from patients with acute myocardial infarction identifies haptoglobin as a potential prognostic biomarker

Prognosis of clinical outcome following myocardial infarction is variable and difficult to predict. We have analyzed the plasma proteome of thirty patients with acute myocardial infarction to search for new prognostic biomarkers. Proteomic analyses of blood samples were performed by 2-D-DiGE after plasma depletion of albumin and immunoglobulins G. New York Heart Association (NYHA) class determined at 1-year follow-up was used to identify patients with heart failure. Principal component analysis and hierarchical clustering of proteomic data revealed that patients could be separated into 3 groups. The 22 differentially expressed proteins involved in this grouping were identified as haptoglobin (Hp) and respective isoforms. The 3 groups of patients had distinct Hp isoforms: patients from group 1 had the α1-α1, patients from group 2 the α2-α1, and patients from group 3 the α2-α2 genotype. This classification was also associated with different total plasma levels of Hp. The presence of the α2 genotype and low plasma levels of Hp was associated with a higher NYHA class and therefore with a detrimental functional outcome after myocardial infarction. A plasma level of Hp below 1.4g/L predicted the occurrence of heart failure (NYHA 2, 3, 4) at 1-year with 100% sensitivity.

Assessment of Procalcitonin to Predict Outcome in Hypothermia-Treated Patients after Cardiac Arrest

Objective. Determine the potential of procalcitonin (PCT) to predict neurological outcome after hypothermia treatment following cardiac arrest. Methods. Retrospective analysis of patient data over a 2-year period. Mortality and neurological outcome of survivors were determined 6 months after cardiac arrest using the Cerebral Performance Category (CPC) score. Results. Data from 53 consecutive patients were analyzed. Median age was 63 (54–71) and 79% were male. Twenty-seven patients had good outcome (CPC ≤ 2) whereas 26 had severe neurological sequelae or died (CPC 3–5). At 48 h, after regaining normothermia, PCT was significantly higher in patients with bad outcome compared to those with good outcome: 3.38 (1.10–24.48) versus 0.28 (0–0.75) ng/mL (P < 0.001). PCT values correlated with bad neurological outcome (r = 0.54, P = 0.00004) and predicted outcome with an area under the curve of 0.84 (95% CI 0.73–0.96). A cutoff point of 1 ng/mL provided a sensitivity of 85% and a specificity of 81%. Above a PCT level of 16 ng/mL, no patient regained consciousness. PCT provided an additive value over simplified acute physiology score II. Conclusions. PCT might be an ancillary marker for outcome prediction after cardiac arrest treated by induced hypothermia.

MicroRNAs in Patients on Chronic Hemodialysis (MINOS Study)

BACKGROUND AND OBJECTIVES Diagnosis of acute myocardial injury with biomarkers is difficult in patients with advanced renal failure. Circulating microRNAs are promising new biomarkers of myocardial injury. It is unknown whether levels of microRNAs are affected in patients undergoing hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS High-sensitivity cardiac troponin T (hsTnT) and cardiac-enriched miR-499 were measured in 41 patients with ESRD undergoing hemodialysis and 41 controls. RESULTS Levels of hsTnT and miR-499 were highly elevated in patients with ESRD compared with controls (>80-fold increase; P<0.001). Among patients with ESRD, 98% had positive hsTnT levels and 46% had positive miR-499 levels. Levels of troponins were not affected by hemodialysis. However, miR-499 levels were decreased after hemodialysis (6.5-fold decrease; P=0.002). CONCLUSIONS Both miR-499 and troponins are elevated in patients with advanced renal failure. However, whereas levels of troponins are unaffected by hemodialysis, this is not the case for miR-499. Therefore, these observations mitigate the potential of miR-499 as a marker of myocardial injury in patients with ESRD.

Prevalence and Correlates of Vitamin D Deficiency and Insufficiency in Luxembourg Adults: Evidence from the Observation of Cardiovascular Risk Factors (ORISCAV-LUX) Study

Evidence on vitamin D status and related risk factors in Luxembourg adults is lacking. This study aimed to determine the prevalence of vitamin D deficiency and insufficiency and related risk factors among healthy adults in Luxembourg. Based on clinicians’ observations, it was hypothesized that vitamin D deficiency and insufficiency might be common in our population, constituting a significant public health concern. A nationally representative random sample of 1432 adults was enrolled in the ORISCAV-LUX study, 2007–2008. The participants were divided into four categories according to their serum concentrations of 25-hydroxyvitamin D [25(OH)D]. Descriptive, univariate and multivariate statistical analyses used weighted methods to account for the stratified sampling scheme. Only 17.1% of the population had a “desirable” serum 25(OH)D level ≥75 nmol/L, whereas 27.1% had “inadequate” [serum 25(OH)D level 50–74 nmol/L], 40.4% had “insufficient” [serum 25(OH)D level 25–49 nmol/L], and 15.5% had “deficient” [serum 25(OH)D level <25 nmol/L)]. The prevalence of vitamin D deficiency was greater among current smokers, obese subjects, those having reduced HDL-cholesterol level and fair/poor self-perception of health, compared to their counterparts. The prevalence of vitamin D insufficiency was additionally higher among nondrinkers of alcohol, Portuguese and subjects from non-European countries. The final multivariate logistic regression analyses revealed that smoking status and obesity were independent correlates of vitamin D deficiency and insufficiency, respectively. Inadequate vitamin D status is highly prevalent among adults in Luxembourg and is associated with specific lifestyle factors. Along with the effect of vitamin D deficiency and insufficiency on the risk of several diseases, cancer and mortality, our findings have practical implications for public health dietary recommendations, and of particular importance for healthcare practitioners and policy makers.

Reverse remodelling through exercise training is more pronounced in non-ischemic heart failure

PurposeMost training studies in patients with chronic heart failure (CHF) do not consider CHF aetiology in the interpretation of the results. About 60% of the patients in those studies have ischemic CHF (IHF) and 40% non-ischemic CHF (NHF). Recently, we conducted a randomized controlled trial to study three different training modalities in 60 patients with severe CHF, with a similar distribution of IHF and NHF patients. In the present post hoc analysis we compared the differences in training results between ischemic and non-ischemic patients.MethodsLeft ventricular ejection fraction (EF), end diastolic volume (EDV), end systolic volume (ESV), measured with radionuclide ventriculography (RNV) and echocardiography, NT-pro BNP, peak oxygen uptake (peak

Cardiometabolic risk: leg fat is protective during childhood.

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