The Discriminatory Ability of Renalase and Biomarkers of Cardiac Remodeling for the Prediction of Ischemia in Chronic Heart Failure Patients With the Regard to the Ejection Fraction.

Background: Renalase has been implicated in chronic heart failure (CHF); however, nothing is known about renalase discriminatory ability and prognostic evaluation. The aims of the study were to assess whether plasma renalase may be validated as a predictor of ischemia in CHF patients stratified to the left ventricular ejection fraction (LVEF) and to determine its discriminatory ability coupled with biomarkers representing a range of heart failure (HF) pathophysiology: brain natriuretic peptide (BNP), soluble suppressor of tumorigenicity (sST2), galectin-3, growth differentiation factor 15 (GDF-15), syndecan-1, and cystatin C. Methods: A total of 77 CHF patients were stratified according to the LVEF and were subjected to exercise stress testing. Receiver operating characteristic curves were constructed, and the areas under curves (AUC) were determined, whereas the calibration was evaluated using the Hosmer-Lemeshow statistic. A DeLong test was performed to compare the AUCs of biomarkers. Results: Independent predictors for ischemia in the total HF cohort were increased plasma concentrations: BNP (p = 0.008), renalase (p = 0.012), sST2 (p = 0.020), galectin-3 (p = 0.018), GDF-15 (p = 0.034), and syndecan-1 (p = 0.024), whereas after adjustments, only BNP (p = 0.010) demonstrated predictive power. In patients with LVEF <45% (HFrEF), independent predictors of ischemia were BNP (p = 0.001), renalase (p < 0.001), sST2 (p = 0.004), galectin-3 (p = 0.003), GDF-15 (p = 0.001), and syndecan-1 (p < 0.001). The AUC of BNP (0.837) was statistically higher compared to those of sST2 (DeLong test: p = 0.042), syndecan-1 (DeLong: p = 0.022), and cystatin C (DeLong: p = 0.022). The AUCs of renalase (0.753), galectin-3 (0.726), and GDF-15 (0.735) were similar and were non-inferior compared to BNP, regarding ischemia prediction. In HFrEF patients, the AUC of BNP (0.980) was statistically higher compared to those of renalase (DeLong: p < 0.001), sST2 (DeLong: p < 0.004), galectin-3 (DeLong: p < 0.001), GDF-15 (DeLong: p = 0.001), syndecan-1 (DeLong: p = 0.009), and cystatin C (DeLong: p = 0.001). The AUC of renalase (0.814) was statistically higher compared to those of galectin-3 (DeLong: p = 0.014) and GDF-15 (DeLong: p = 0.046) and similar to that of sST2. No significant results were obtained in the patients with LVEF >45%. Conclusion: Plasma renalase concentration provided significant discrimination for the prediction of ischemia in patients with CHF and appeared to have similar discriminatory potential to that of BNP. Although further confirmatory studies are warranted, renalase seems to be a relevant biomarker for ischemia prediction, implying its potential contribution to ischemia-risk stratification.

Identification of clinical and paraclinical findings predictive for headache occurrence during spontaneous subarachnoid hemorrhage.

OBJECTIVES: Headache is recognized as the main but unwarranted symptom of subarachnoid hemorrhage (SAH). There are no enough findings identified as predictive for headache occurrence in SAH. We evaluated the clinical and paraclinical factors predictive for headache occurrence in SAH. PATIENTS AND METHODS: We retrospectively analyzed medical records of 431 consecutive non traumatic SAH patients (264 females and 167 males), ages from 19 to 91 years, presenting with headache (70.3%) and without headache (29.7%) during period of 11years. RESULTS: Among all tested parameters, as negative predictors for headache occurrence were recognized: patients' ages (OR 0.97 [95%CI: 0.96-0.99], p=0.025), persistence of coagulation abnormality (OR 0.23 [95%CI: 0.08-0.67], p=0.006), atrial fibrilation (OR 0.23 [95%CI: 0.09-0.59], p=0.002), chronic renal failure (OR 0.26 [95%CI: 0.09-0.76], p=0.014) and more diseases (OR 0.11 [95%CI: 0.04-0.32], p<0.0001), as higher clinical score (OR 0.94 [95%CI: 0.90-0.99], p=0.018) including positive neurological findings (OR 0.34 [95%CI: 0.21-0.55], p<0.001) and loss of consciousness (OR 0.22 [95%CI: 0.12-0.39], p<0.001) at the SAH onset, while the complaint of neck stiffness was identified as its positive predictor (OR 1.93 [95%CI: 1.19-3.10], p=0.007). CONCLUSIONS: Although diagnosis based solely on clinical presentation is not reliable and speculative, our findings could provide physicians with evidence to consider SAH not only in conditions of its headache occurrence but also in those with headache absence.

Association of serum bilirubin and uric acid levels changes during neuroinflammation in patients with initial and relapsed demyelination attacks.

In order to examine the endogenous antioxidants values in the earliest phase of demyelination, we have determined bilirubin and uric acid (UA) serum values in the patients with clinically isolated syndrome (CIS) and relapsing remitting multiple sclerosis (RRMS), regarding their clinical disability, measured by Extended Disability Status Scale (EDSS), Magnetic Resonance Imaging (MRI), disease duration, gender and other parameters. The bilirubin and UA levels were lower in CIS and RRMS patients than in control group, whether male or female (p < 0.05). The bilirubin and UA levels were decreased in RRMS compared to CIS patients (p < 0.05). Regarding EDSS, MRI and disease duration, obtained values of bilirubin and UA were higher in both study groups in patients with lower EDSS, lower MRI lesion number and shorter disease duration (p < 0.05). The greatest significance in decreased bilirubin and UA levels was observed in female compared to male patients, in both study groups (p < 0.05). The results suggest negative linear correlation between bilirubin and UA levels and disease duration, EDSS and MRI in CIS (p < 0.01), with the same correlation between bilirubin and UA levels and disease duration in RRMS patients (p < 0.01). There was also significant correlation between bilirubin level and MRI findings and UA levels and EDSS in RRMS patients (p < 0.01). The obtained results point to the importance of endogenous antioxidants in the outbreak and course of neuroinflammation. This could be favorable for the new pathogenetically conditioned neuroinflammatory therapy concepts which do not initially rely only on immunomodulatory, but also on the antioxidative effects.