White blood cells in a healthy adolescent population according to social and health characteristics.

BACKGROUND: The immune system constitutes a sensory system both for heritable and non-heritable factors. Among the latter, social and environmental determinants of health may influence and shape the immune system in early life. To study the relationship between leukocytes and determinants of health in adolescence, we assessed total and differential white blood cells (WBC) according to social and environmental determinants of health in a healthy adolescent population. METHODS: As part of the population-based cohort Epidemiological Health Investigation of Teenagers in Porto (EPITeen), 1213 adolescents were evaluated at the age of 13. Total and differential WBC were evaluated through a venous blood sample using an automated blood counter (Sysmex®XE-5000, Hyogo, Japan). Sociodemographic, behavioral, and clinical data were collected through self-administered questionnaires. RESULTS: Participants with better socioeconomic conditions (enrolled at private schools or higher parental education) had significantly lower total WBC levels, and the latter showed a lower percentage of neutrophils and higher percentage of lymphocytes. Those who practiced sports had significantly lower total WBC levels and neutrophil percentage, as well as a significantly higher percentage of eosinophils and lymphocytes. Adolescents with chronic disease, chronic medication, or allergic diseases had a significantly higher percentage of eosinophils and a lower percentage of monocytes. With increasing body mass index and systemic inflammation, we found a significant increase in total WBC levels. CONCLUSION: WBC linked to different immune response patterns are associated with several social and environmental determinants of health in adolescence.

Creatinine Clearance in Acute Brain Injury: A Comparison of Methods.

BACKGROUND: Currently, the measurement of glomerular filtration rate is very complex and costly, so its daily evaluation is performed using endogenous markers, of which creatinine is the most frequently used. It allows the estimation of glomerular filtration rate by means of its clearance or by formulas based on its serum and urine concentration. Augmented renal clearance (ARC) is frequent among critically ill patients and is defined as creatinine clearance (CrCl) > 130 ml/min/1.73 m2. The aim of this study was to compare measured CrCl (MCC) and estimated CrCl obtained with the Cockcroft-Gault formula (CG), the Modification of Diet in Renal Disease Study equation (MDRD), and the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) in patients with severe traumatic brain injury and nontraumatic subarachnoid hemorrhage. The second aim was to assess the incidence of ARC in this population of neurocritical patients. METHODS: This was a prospective, observational, single center study from a cohort of 74 patients admitted to the neurocritical intensive care unit due to traumatic brain injury or subarachnoid hemorrhage. Serum creatinine (at 7 a.m.) and a 6-h urine collection were analyzed, and CrCl was measured and estimated by using CG, MDRD, and CKD-EPI. The intraclass correlation coefficient (ICC) was evaluated for each pair, and Bland-Altman plots were used to assess clinical significance. RESULTS: Among 74 patients, the median age was 53 (interquartile range [IQR] 36-65), and the median Glasgow Coma Scale score at admission was 6. The median MCC at admission was 176 (IQR 135-214). The medians of CG, MDRD and CKD-EPI were, respectively, 129 ml/min/1.73 m2 (IQR 95-176), 158 (IQR 115-202), and 116 (97-132). An ICC was applied to evaluate the correlation between MCC and estimated methods and showed a weak correlation between MCC and estimated CrCl obtained with the three different methods. The strongest ICC statistical correlation was found between MCC and MDRD, and the weakest correlation was found between MCC and CKD-EPI. Bland-Altman plots showed that differences between each pair were not clinically acceptable. ARC was present in 78% of measurements, using MCC. A weak correlation was observed between MCC and calculated CrCl. CG, MDRD, and CKD-EPI overestimated MCC when MCC ≤ 130 ml/min/1.73 m2 and underestimated it when MCC > 130 ml/min/1.73 m2. CONCLUSIONS: In this population, there was a weak statistical correlation between measured and estimated methods. In patients with ARC, formulas underestimated MCC. MCC should probably be the preferred methodology for renal function assessment in the clinical setting to better adjust drug dosage and guarantee drug effectiveness.

How the metabolic phenotype in adulthood is affected by long-lasting immunological trajectories since adolescence.

A close relationship between immune and metabolic systems has been perceived in the recent past. We aimed to assess whether the immunological trajectories of circulating white blood cells (WBC) started in adolescence, affects the metabolic phenotype in adulthood. We used data from 1183 participants of the population-based EPITeen cohort, evaluated at 13, 17, 21, 24 and 27 years of age. The Immunological trajectories from 13 to 27 years old were identified by mixed-effects models, being their association with metabolic features at 27 years old measured by logistic regression. The Higher Inflammatory Activation trajectory (HIA trajectory) had the highest percentage of individuals with metabolic syndrome, while Lowest Levels of WBC trajectory (LLWBC trajectory) showed the lowest percentage. Participants with HIA trajectory had significantly higher triglycerides, waist circumference, serum uric acid and BMI. After adjustment for sex and sports practice and hs-CRP, the odds of having one or more metabolic features in adulthood was significantly lower in LLWBC trajectory. Individuals with immunological trajectories of WBC linked with a pattern of higher immune activation showed a less favorable metabolic profile, while those with the lowest levels of WBC were less likely to have metabolic risk factors in adulthood.

Pericardial Fluid Annexin A1 Is a Marker of Atrial Fibrillation in Aortic Stenosis: A Proteomics Analysis.

Atrial fibrillation (AF) is the most common arrhythmia with adverse clinical outcomes. Pericardial fluid (PF) mirrors the heart's pathophysiological status due to its proximity. This study aimed to characterise the PF proteome to identify new biomarkers of disease. Eighty-three patients submitted to aortic valve replacement surgery with severe aortic stenosis were selected, and their baseline echocardiographic and clinical variables were documented. Thirteen samples were selected blindly for proteome characterisation following a shotgun (GeLC-MS/MS) and a label-free quantification approach (LFQ). According to previous AF history, a partial least squares discriminant analysis (PLS-DA) was conducted, and the top 15 variables important in projection were identified. To inquire potential biomarkers, ROC curves were designed using LFQ data. Target proteins were further validated by ELISA, in both pericardial fluid and serum. Proteome analysis uncovered nine proteins up- and downregulated ≥2-fold. Annexin A1, annexin A2, and vimentin were among the top 15 most important variables for group discrimination in PLS-DA. Protein-protein interaction and gene ontology enrichment analysis presented functional interaction among identified proteins, which were all part of focal adhesion sites. Annexin A1 was increased in the pericardial fluid of AF patients but not in serum when quantified by ELISA. Annexin A1 is a novel pericardial fluid biomarker of AF in patients with severe aortic stenosis.

CA-125 variation in acute heart failure: a single-centre analysis.

AIMS: A decrease in carbohydrate antigen 125 (CA-125) predicts survival advantage in chronic heart failure (HF); the impact of its variation in acute HF is unknown. We studied the association of CA-125 decrease with prognosis in acute HF. METHODS AND RESULTS: We studied acute hospitalized HF patients. Predictors of admission and discharge CA-125 were determined by linear regression. Follow-up was 1 year; endpoint was all-cause death. The association of admission and discharge CA-125 with mortality was assessed using a Cox-regression analysis. A Cox-regression analysis was also used to assess the prognostic impact of CA-125 decrease during hospitalization. Analysis was stratified by length of hospital stay (LOS). We studied 363 patients, 51.5% male, mean age 75 ± 12 years, 51.5% ischaemic, 30.0% with preserved ejection fraction, and 57.3% with reduced ejection fraction; patients presented elevated comorbidity burden. Median LOS was 7 (5-11) days. In the subgroup of 262 patients with CA-125 measured both at admission and at discharge, we reported a significant increase in its levels: 56.0 (26.0-160.7) U/mL to 74.0 (32.3-195.0) U/mL. Independent predictors of admission CA-125 were higher BNP and lower creatinine. Predictors of discharge CA-125 were higher discharge BNP, lower discharge albumin, and younger age. Both admission and discharge CA-125 predicted mortality. During follow-up, 75 (31.8%) patients died. A decrease in CA-125 predicted a 68% reduction in the 1 year death risk only in patients with LOS > 10 days. CONCLUSIONS: Our results suggest that an early re-evaluation (>10 days) with CA-125 measurement after an acute HF hospitalization may be of interest in patient management.

The prognostic impact of magnesium in acute heart failure is different according to the presence of diabetes mellitus.

Background: Hypermagnesemia predicts mortality in chronic heart failure (HF); however, in acute HF, magnesium does not seem to be outcome-associated. Diabetes mellitus (DM) frequently associates with altered magnesium status. We hypothesized that DM might influence the prognostic impact of magnesium in acute HF. Methods: This is a retrospective cohort study of hospitalized patients with acute HF. Patients without data on admission serum magnesium were excluded. Follow-up: 1 year from hospital admission. Primary end point: all-cause mortality. Patients were divided according to median serum magnesium (1.64 mEq/L). The Kaplan-Meier survival method was used to determine survival curves according to magnesium levels. The analysis was stratified according to the presence of DM. A multivariable Cox regression analysis was used to study the prognostic impact of magnesium. Results: We studied 606 patients. The mean age was 76 ± 12 years, 44.1% were male, 50.7% had DM, and 232 (38.3%) died during follow-up. Median magnesium was 1.64 (1.48-1.79) mEq/L. Patients with magnesium ≥1.64 mEq/L had higher 1-year mortality [141 (46.4%) vs 91 (30.1%), P < .001]. After adjustments for age, sex, history of atrial fibrillation, systolic blood pressure, heart rate, ischemic etiology, B-type natriuretic peptide, estimated glomerular filtration rate, alcohol consumption, antihyperglycaemic agents or glycated hemoglobin, admission glycemia, New York Heart Association class IV, and severe left ventricle systolic dysfunction, serum magnesium ≥1.64 mEq/L was associated with higher mortality only in patients with DM: HR 1.89 (95% confidence interval: 1.19-3.00), P = .007, and 1.27 (95% confidence interval: 0.83-1.94) and P = .26 for non-DM patients. The results were similar if magnesium was analyzed as a continuous variable. Per 0.1 mEq/L increase in magnesium levels, patients with DM had 13% increased risk of 1-year mortality. Conclusions: Higher magnesium levels were associated with worse prognosis only in HF patients with DM.

Immunological Trajectories of White Blood Cells from Adolescence to Adulthood: Description and Determinants.

BACKGROUND: The immune system gradually matures early in life in the face of internal and external stimuli. Whether the immune responses are lasting and stable during the course of life is still unclear. METHODS: As part of the EPITeen cohort, 1183 adolescents were prospectively evaluated at the ages of 13, 17, 21, 24 and 27. Sociodemographic, behavioral and clinical data were collected by self- and face-to-face-administered questionnaires, along with a physical examination comprising anthropometric measurements and blood sample collections. Mixed-effects models were used to identify individual trajectories of white blood cells (WBC) and finite Gaussian mixture models were used to identify the clusters of individual trajectories. RESULTS: Participants were allocated into six clusters based on the individual trajectories of WBC distribution. Higher Inflammatory Activation Cluster (11.4%) had the highest total WBC count and neutrophils percentage, as well as the lowest percentage of lymphocytes. These participants had significantly higher odds of being overweight [OR = 2.44, 95%CI:1.51-3.92]. Lowest Levels of WBC Cluster (24.1%) had the lowest total WBC count, being characterized by a higher participation on sports [OR = 1.54, 95%CI:1.12-2.13]. Highest Proportion of Eosinophils Cluster (20.1%) had the highest eosinophils percentage and the highest likelihood of having been diagnosed with a chronic disease [OR = 2.11, 95%CI:1.43-3.13], namely "asthma or allergies" [OR = 14.0 (1.73, 112.2]. Lowest Proportion of Eosinophils Cluster (29.1%) had the lowest percentage of eosinophils and basophils, as well as the highest lymphocyte proportion. Participants in the Undefined Cluster (13.8%) showed the highest percentage of monocytes and basophils and were also characterized by significant lower odds of having parents with 7-9 years of schooling [OR = 0.56, (0.32, 0.99]. CONCLUSIONS: In this study we identified distinct immunological trajectories of WBC from adolescence to adulthood that were associated with social, clinical and behavioral determinants. These results suggest that these immunological trajectories are defined early in life, being dependent on the exposures.

Pericardial NT-Pro-BNP and GDF-15 as Biomarkers of Atrial Fibrillation and Atrial Matrix Remodeling in Aortic Stenosis.

AIMS: This study aimed to evaluate the association of GDF-15 and NT-pro-BNP in two different biological matrices with AF in severe aortic stenosis patients undergoing aortic valve replacement surgery (AVR), its association with atrial matrix remodeling, as well as with 30-day postoperative outcomes. MAIN METHODS: One hundred and twenty-six patients between 2009 and 2019 with severe aortic stenosis undergoing AVR surgery in a tertiary hospital were assessed. KEY FINDINGS: pericardial fluid GDF-15 and pericardial fluid and serum NT-pro-BNP were increased in AF patients with aortic stenosis. COL1A1 and COL3A1 gene expression increased when pericardial fluid NT-pro-BNP values were higher. TIMP4 was positively correlated with pericardial fluid GDF-15. SIGNIFICANCE: GDF-15 and NT-pro-BNP in the pericardial fluid are biomarkers of atrial fibrillation in aortic stenosis and correlate with atrial matrix remodeling. AKI is predicted by both serum and pericardial fluid GDF-15.

Dynamics of growth differentiation factor 15 in acute heart failure.

AIMS: Risk stratification in acute heart failure (HF) patients can help to decide therapies and time for discharge. The potential of growth differentiation factor 15 (GDF-15) in HF has been previously shown. We aimed to study the importance of GDF-15-level variations in acute HF patients. METHODS AND RESULTS: We retrospectively evaluated a cohort of patients hospitalized due to acute HF. GDF-15 was measured both at admission and on the discharge day. Patients were followed-up during a 3 year period. The endpoint under analysis was all-cause mortality. GDF-15 variation is equal to [(admission GDF-15 - discharge GDF-15)∕admission GDF-15] × 100. Variation was categorized in levels of increase or decrease of GDF-15. Patients were cross-classified according to admission and discharge GDF-15 cut-off points. A Cox regression analysis was used to assess the prognostic impact of GDF-15 variation and the impact of both admission and discharge GDF-15 according to the cross-classification. We studied a group of 249 patients with high co-morbidity burden. Eighty-one patients died at 1 year and 147 within 3 years. There was a modest decrease in GDF-15 during hospitalization from a median value of 4087 to 3671 ng/mL (P = 0.02). No association existed between GDF-15 variation and mortality. In multivariate analysis, patients with admission GDF-15 ≥ 3500 ng/mL and discharge GDF-15 ≥ 3000 ng/mL had a significantly higher 1 year death risk when compared with the remaining-hazard ratio = 2.59 (95% confidence interval: 1.41-4.76)-and a 3 year 1.76 (95% confidence interval: 1.08-2.87) higher death risk compared with those with both values below the cut-off. CONCLUSIONS: Growth differentiation factor 15 decreased during an acute HF hospitalization, but its variation had no prognostic implications. The knowledge of both admission and discharge GDF-15 added meaningful information to patients' risk stratification.

Gut microbiota changes after metabolic surgery in adult diabetic patients with mild obesity: a randomised controlled trial.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30-35 kg/m2). METHODS: DM2 was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass-RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing. RESULTS: Twenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p < 0.001) and HbA1c was 6.2 vs. 7.7% (p < 0.001) respectively. We observed a continuous increase of genus richness after RYGB up until M12. In the medical arm, genus richness ended-up being significantly lower at M12. Composition analysis indicated significant changes of the overall microbial ecosystem (permanova p = 0.004, [R2 = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages. CONCLUSIONS: This was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level. TRIAL REGISTRATION: ISRCTN53984585.

Inflammatory Response Assessment in Patients with COVID-19 Under Extracorporeal Membrane Oxygenation Support.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO), could be extremely helpful in the management of COVID-19 patients with refractory hypoxemic respiratory failure; however, to date, evidence on the true effecttiveness of ECMO in the COVID19 setting still hangs in the balance. METHODS: This was a prospective cohort study of 39 COVID-19 patients admitted to the intensive care unit (ICU) in an experienced ECMO center at a tertiary hospital during March/April 2020. Among the recruited participants, 10 (25.6%) required ECMO (ICU-ECMO group) and 29 (74.4%) did not have ECMO support (ICU group). Immunological parameters were assessed both at ICU admission and on a daily basis for 7 consecutive days. RESULTS: The absolute lymphocyte count increased significantly in the ICU-ECMO group compared to the ICU group in which it remained relatively stable: ß for the time variable was 127.1 [95% CI 68.9 - 185.3], p < 0.001 and for the interaction term -141.36 [-208.95 - -73.77], p < 0.001. On the other hand, globally, no significant differences were observed over time for the lymphocyte percentage, although it was higher in the ICU patients. Neutrophil counts were overall higher in the ICU-ECMO group (ß -4,275.38 [-6,845.21 - 1,705.55], p = 0.001). In regard to neutrophil percentage, a significant decrease over time was reported (ß -1.76 [-3.16 - -0.36], p = 0.014), namely in the ICU-ECMO group (ß for the interaction 2.09 [0.45 - 3.73], p = 0.013). CONCLUSIONS: Herein, we found ECMO support seems to provide a less aggressive immune response in COVID-19 patients with severe and refractory respiratory dysfunction.

Parental education associated with immune function in adolescence.

BACKGROUND: The immune system is affected and shaped by several internal and external factors. Among the external variables, the socioeconomic status is known to influence the immune system since the early years of life and throughout life. METHODS: In this study, we assessed the relationship between parental education with the white blood cells and its subtypes in 1213 adolescents from the EPITeen cohort, assessed at the age of 13. Beta coefficients (ß) and 95% confidence intervals (CI) were fitted using linear regression models to quantify the association and were adjusted for sex, body mass index and chronic disease. RESULTS: After adjustment, parental education presented a negative association with white blood cells, which was significant among those with higher high-sensitivity C-reactive protein (hs-CRP) median levels [-0.05 mg/l (95% CI -0.08, -0.01)]. On the contrary, a positive association with lymphocytes was observed, which was, significant among those with lower hs-CRP [0.17 mg/l (95% CI 0.02, 0.32)]. A neutrophil-to-lymphocyte ratio significant decrease was also observed with the increment of parental education (P<0.001). CONCLUSION: We found that parental education was positively associated with a higher proportion of lymphocytes and a lower proportion of neutrophils, suggesting that parental education is associated with offsprinǵs innate immune system regulation. These results may contribute to clarify the relationships between childhood socioeconomic status and increased risk of adverse cardiovascular outcomes and other immune-related diseases.

C-reactive protein decrease associates with mortality reduction only in heart failure with preserved ejection fraction.

AIMS: The prognostic role of high-sensitivity C-reactive protein (hsCRP) in acute heart failure is less well established than for chronic heart failure and the impact of its variation is unknown. We studied the impact of hsCRP variation in acute heart failure and whether it differed according to left ventricular function. METHODS: We analyzed patients prospectively included in an acute heart failure registry. Admission and discharge hsCRP were evaluated as part of the registry's protocol and its relative variation (ΔhsCRP) was assessed. ΔhsCRP during hospitalization =  [(admission hsCRP - discharge hsCRP)/admission hsCRP] × 100. Endpoint: all-cause death; follow-up: 3 years. A multivariate Cox-regression model was used to assess the prognostic value of ΔhsCRP (continuous and categorical variable: cut-off 40% decrease); analysis was stratified according to ventricular function. RESULTS: We studied 439 patients: mean age 75 years, 50.1% men and 69.2% had heart failure with reduced ejection fraction (HFrEF). Median discharge hsCRP was 12.4 mg/l and median ΔhsCRP was ∼40%. During follow-up 247 patients (56.3%) died: 73 (54.1%) heart failure with preserved ejection fraction (HFpEF) patients and 174 (57.2%) HFrEF patients. The multivariate-adjusted hazard ratio of 3-year mortality in HFpEF patients with hsCRP decrease of at least 40% during hospitalization was 0.56 (95% CI 0.32-0.99). A decrease of at least 40% in hsCRP was not mortality-associated in HFrEF patients. There was interaction between ΔhsCRP and left ventricular ejection fraction. CONCLUSION: A decrease of at least 40% in hsCRP in acute heart failure was associated with a 44% decrease in 3-year death risk in HFpEF patients. No association between ΔhsCRP and prognosis existed in HFrEF patients. Inflammation appears to play a different role according to left ventricular function.

Proper zinc evaluation in clinical practice: Effect of sample type and it's stability.

Zinc (Zn) is a ubiquitous element that plays a vital role in the growth and development of human body. Traditionally, Zn has been measured in plasma samples using "trace element" dedicated sampling tubes. However, the recent increase in its assessment leads to the need to use others than plasma samples and the use of sera could be a justified and valid alternative. We evaluated the differences between plasma and serum, for Zn quantification. 307 blood paired samples from patients enrolled for the treatment of obesity-related pathology at our out-patient department were assessed. The quantification of Zn was performed by Flame atomic absorption spectroscopy. Using 123 serum samples randomly selected from our own biobank and stored at -80 °C for 5 years, we further investigated the long-term stability of serum Zn. The mean result for Zn was 77.8 ±â€¯13.2 µg·dL-1 and 77.4 ±â€¯12.8 µg·dL-1, respectively for plasma and for serum, (p = 0.43). Bland-Altman analyses demonstrated excellent concordance of the assay in the two different blood matrices. The mean difference ±â€¯SD between serum and plasma matrices was 0.32 ±â€¯3.40 µg·dL-1. The assessment of serum Zn long-term stability indicated a significant change after 5 years storage. The mean value was 74.2 ±â€¯10.9 µg·dL-1 for fresh samples and 83.3 ±â€¯10.9 µg·dL-1 after 5 years of storage at -80 °C, corresponding to a mean difference of +9.1 µg·dL-1(+10,9%, p < 0.05). The increase in Zn values described after long-term storage has to be considered though that should not have a significant clinical value. In conclusion, the routine measurement of Zn can be made in an accurate way using a serum sample, without the need for a specific tube for trace elements assessment.

Is there a C-reactive protein value beyond which one should consider infection as the cause of acute heart failure?

BACKGROUND: Heart Failure (HF) is a low grade inflammatory condition. High sensitivity C-reactive protein (hsCRP) is an established marker of inflammation. A cut-off value of hsCRP beyond which an infection should be sought has never been studied in HF. We aimed to determine the best hsCRP cut-off for infection prediction in acute HF. METHODS: We analyzed patients included in an acute HF registry - EDIFICA (Estratificação de Doentes com InsuFIciência Cardíaca Aguda). Admission hsCRP measurement was available as part of the registry's protocol. Patients with acute coronary syndrome as the cause of acute HF were excluded from the registry. Infection was considered according to the diagnosis registered in the discharge record. A receiver-operating characteristic (ROC) curve was used to determine the best hsCRP cut-off for infection prediction. RESULTS: We studied 615 patients. Mean age was 76 years, 45.2% were male, 60.3% had systolic dysfunction. Median admission hsCRP was 20.3 (9.5-55.5)mg/L; in 41.6% the cause of decompensation was an infection. The area under the ROC curve for admission hsCRP in the prediction of infection was 0.79 (0.76-0.83); the best hsCRP cut-off was 25 mg/L with a sensitivity of 72.7%, specificity 77.2%, positive predictive value 69.4% and negative predictive value 79.9%. Age and elevated hsCRP independently associated with an infection as the precipitant of acute HF. CONCLUSIONS: We suggest 25 mg/L as a cut-off beyond which an infection should be sought underlying acute HF. Almost 80% of the patients with hsCRP< 25 mg/L are not infected and 69.4% of those with higher hsCRP have a concomitant infection.

The role of biomarkers in dilated cardiomyopathy: Assessment of clinical severity and reverse remodeling.

INTRODUCTION: Biomarkers in dilated cardiomyopathy (DCM) reflect various pathobiological processes, including neurohormonal activation, oxidative stress, matrix remodeling, myocyte injury and myocyte stretch. We assessed the role of biomarkers in clinical and echocardiographic parameters and in left ventricular (LV) reverse remodeling (LVRR). METHODS: In this prospective study of 50 DCM patients (28 men, aged 59±10 years) with LV ejection fraction (LVEF) <40%, LVRR was defined as an increase of >10 U in LVEF after optimal medical therapy. RESULTS: Baseline LVEF was 25.4±9.8% and LV end-diastolic diameter (LVEDD)/body surface area (BSA) was 34.2±4.5 mm/m2. LVRR occurred in 34% of patients within 17.6±15.6 months. No correlation was found between B-type natriuretic peptide (BNP), 25-hydroxyvitamin D (25(OH)D), CA-125, high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) [Lp(a)], noradrenaline, adrenaline, renin or aldosterone and LVRR. Patients in NYHA class III or IV, with pulmonary congestion or ankle edema, had higher CA-125, cystatin C, BNP and hs-CRP levels (p<0.05). CA-125 was correlated with BNP (r=0.61), hs-CRP (r=0.56) and uric acid (r=0.52) (all p=0.01). BNP correlated directly with LVEDD (r=0.49), LV volumes (r=0.51), pulmonary artery systolic pressure (PASP) (r=0.43) and E/e' (r=0.31), and was inversely correlated with LVEF (r=-0.50) and e' velocity (r=-0.32) (p<0.05). CA-125 was positively correlated with left atrial volume/BSA (r=0.46), E/A ratio (r=0.60) and PASP (r=0.49) (p<0.05). CONCLUSIONS: No correlation was found between biomarkers and LVRR, but CA-125, BNP and hs-CRP were predictors of clinical severity and congestion. BNP correlated with parameters of systolic and diastolic dysfunction, while CA-125 correlated with measures of diastolic dysfunction.