Identification of six cardiovascular risk biomarkers in the young population: A promising tool for early prevention.

BACKGROUND AND AIMS: The predictive value of traditional CV risk calculators is limited. Novel indicators of CVD progression are needed particularly in the young population. The main aim of this study was the identification of a molecular profile with added value to classical CV risk estimation. METHODS: Eighty-one subjects (30-50 years) were classified in 3 groups according to their CV risk: healthy subjects; individuals with CV risk factors; and those who had suffered a previous CV event. The urine proteome was quantitatively analyzed and significantly altered proteins were identified between patients' groups, either related to CV risk or established organ damage. Target-MS and ELISA were used for confirmation in independent patients' cohorts. Systems Biology Analysis (SBA) was carried out to identify functional categories behind CVD. RESULTS: 4309 proteins were identified, 75 of them differentially expressed. ADX, ECP, FETUB, GDF15, GUAD and NOTCH1 compose a fingerprint positively correlating with lifetime risk estimate (LTR QRISK). Best performance ROC curve was obtained when ECP, GDF15 and GUAD were combined (AUC = 0.96). SBA revealed oxidative stress response, dilated cardiomyopathy, signaling by Wnt and proteasome, as main functional processes related to CV risk. CONCLUSIONS: A novel urinary protein signature is shown, which correlates with CV risk estimation in young individuals. Pending further confirmation, this six-protein-panel could help in CV risk assessment.

Inflammation dynamics after praziquantel treatment of Schistosoma haematobium reflected by urinary eosinophil cationic protein.

Background: This cohort study assessed urinary eosinophil cationic protein (ECP) as an indicator for urinary tract morbidity and inflammation indication related to single-dose or dual-dose praziquantel (PZQ) treatment. Methods: Urinary ECP was measured at baseline, 24 h and 9 weeks after treatment (baseline 305, follow-up 204 participants, ages 2-40 years). Results: ECP was significantly associated with the intensity of infection at baseline (p<0.05). Levels at baseline were 8.31 times higher (p<0.01) in participants with bladder morbidity than in those without. There was no correlation with kidney morbidity and no significant effect of a repeated dose of PZQ 40 mg/kg. Baseline ECP and ECP after 9 weeks were associated with microhaematuria (geometric mean ratio at baseline 7.56 [95% confidence limit {CL} 2.34-24.45]; p<0.01) and macrohaematuria (geometric mean ratio at baseline 6.22 [95% CL 2.71-14.24]; p<0.001). Mean levels of ECP dropped significantly during the first follow-up period and far less so in the second follow-up period (mean ECP at baseline: 70.8 ng/mL; ECP at 24 h: 24.5 ng/mL; ECP at 9 weeks: 14.6 ng/mL). Conclusion: The urine ECP decrease happened immediately after treatment, reflecting the rapid action of PZQ on eggs in the bladder tissue. ECP in urine can be used as an indirect marker of the degree of local inflammatory reaction in the bladder and is not significantly affected by a repeated dose of PZQ.

Eosinophil cationic protein, soluble egg antigen, circulating anodic antigen, and egg excretion in male urogenital schistosomiasis.

Markers of male genital schistosomiasis (MGS) are needed to elucidate the consequences for reproductive health. Eosinophil cationic protein (ECP) and soluble egg antigen (SEA) in urine and semen, and circulating anodic antigen (CAA) in serum were assessed as MGS markers. Egg counts, ECP, and SEA in urine and CAA in serum, correlated positively. Seminal egg excretion exhibited marked day-to-day variations, but counts correlated positively with urinary egg counts and SEA in semen and with CAA. Positive predictive values with reference to seminal egg excretion were as follows: seminal ECP (52%), seminal SEA (83%), CAA (97%), and urinary egg excretion (82%). SEA in semen and CAA in serum constitute potential markers of MGS. However, urine egg counts as an indirect marker of MGS remains the preferred diagnostic method from a public health perspective.

Increased bronchial NO output in severe atopic eczema in children and adolescents.

Atopic children have an increased risk for asthma, which is preceded by bronchial inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess alveolar NO concentration and bronchial NO flux, which reflect inflammation in lung periphery and central airways, respectively. Exhaled breath condensate is another non-invasive method to measure lung inflammation. The purpose of the present study was to find out if the severity of atopic eczema is associated with lung inflammation that can be observed with these non-invasive tests. We studied 81 patients (7-22 yr old) with atopic eczema and increased wheat-specific IgE (>or=0.4 kUA/l) and no diagnosis of asthma. Exhaled NO was measured at multiple exhalation flow rates, and bronchial NO flux and alveolar NO concentration were calculated. Cysteinyl-leukotriene concentrations were measured in exhaled breath condensate. The patients were divided into two groups according to the severity of atopic eczema. Patients with severe atopic eczema had enhanced bronchial NO output as compared with patients with mild eczema (2.1 +/- 0.5 vs. 0.9 +/- 0.1, p = 0.003). No statistically significant differences in alveolar NO concentrations were found between the groups. In the whole group of patients, the bronchial NO output correlated positively with serum eosinophil protein X (r(s) = 0.450, p < 0.001), serum eosinophil cationic protein (r(s) = 0.393, p < 0.001), serum total IgE (r(s) = 0.268, p = 0.016) and with urine eosinophil protein X (r(s) = 0.279, p = 0.012), but not with lung function. Alveolar NO concentration correlated positively with serum eosinophil protein X (r(s) = 0.444, p < 0.001) and with serum eosinophil cationic protein (r(s) = 0.362, p = 0.001). Measurable cysteinyl-leukotriene concentrations in exhaled breath condensate were found only in one-third of the patients, and there were no differences between the two groups. The results show that increased bronchial NO output is associated with eosinophilic inflammation and severe atopic eczema in patients without established asthma.

Relationships between cotinine, lower respiratory tract infection, and eosinophil cationic protein in children.

INTRODUCTION: The aim of this study was to investigate the effect of passive smoking on urine eosinophil cationic protein (u-ECP) in children with lower respiratory tract infections (LRTI). METHOD: This was a case-control study. The study cohort consisted of 150 children with LRTI (case group) and 150 healthy children (control), all from a urban setting. The statistical parameters were: a minimum of 139 children for a 95% confidence interval (95% CI), 80% power, and a possible exposure prevalence of 50%. The u-cotinine and u-ECP levels were measured by radioimmunoassay and fluoroimmunoassay methods, respectively. Data were analyzed by the McNemar chi-square test, t-test, and Pearson correlation. RESULTS: When the generally accepted cut-off level of 30 ng/mg urinary cotinine/creatinine was applied, 87.3% of the children with LRTI and 84.7% of healthy children were passive smokers. Using a cut-off level of 60 ng/mg, passive smoking increased the prevalence of LRTI by 4.7-fold (p=0.000). The mean u-ECP values were significantly higher in the case group than in the healthy control group (p=0.018). A positive association was found between u-cotinine and u-ECP values in children with LRTI (p=0.034). CONCLUSION: The results of this study indicate that passive smoking may play an important role in the development of respiratory infections and can cause airway inflammation in children with existing LRTI.