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Background: To assess whether serum osteoprotegerin (OPG) and/or fetuin-A predict mortality and cardiovascular (CV) morbidity and mortality in hemodialysis patients., Methods: Multicenter, observational, prospective study that included 220 hemodialysis patients followed up for up to 6 years. Serum OPG and fetuin-A levels were measured at baseline and their possible association with clinical characteristics, CV risk biomarkers, carotid ultrasonographic findings, as well as their association with overall and CV mortality and CV events were assessed., Results: During a mean follow-up of 3.22 ± 1.91 years, there were 74 deaths (33.6%) and 86 new cardiovascular events. In the Kaplan-Meier survival analysis, the highest tertile of OPG levels was associated with higher overall mortality (p = 0.005), as well as a higher, although non-significant, incidence of CV events and CV mortality. In contrast, fetuin-A levels did not predict any of these events. OPG levels were directly associated with age, the Charlson comorbidity index (CCI), prevalent cardiovascular disease, carotid intima-media thickness, adiponectin, troponin-I and brain natriuretic peptide (BNP). OPG showed a negative correlation with left ventricular ejection fraction (LVEF) and phosphate levels. In the multivariate Cox proportional hazard analysis, all-cause mortality was associated with the highest tertile of OPG (HR:1.957, p = 0.018), age (HR:1.031, p = 0.036), smoking history (HR:2.122, p = 0.005), the CCI (HR:1.254, p = 0.004), troponin-I (HR:3.894, p = 0.042), IL-18 (HR:1.061, p < 0.001) and albumin levels (HR:0.886, p < 0.001). In the bootstrapping Cox regression analysis, the best cut-off value of OPG associated with mortality was 17.69 pmol/L (95%CI: 5.1-18.02)., Conclusions: OPG, but not fetuin-A levels, are independently associated with overall mortality, as well as clinical and subclinical atherosclerosis and cardiac function, in prevalent hemodialysis patients.

Cardiovascular disease, closely related to an early appearance of hypertension, is the most common mortality cause among autosomal dominant polycystic kidney disease patients (ADPKD). The development of hypertension is related to an increase in renal volume. Whether the increasing in the renal volume before the onset of hypertension leads to a major cardiovascular risk in ADPKD patients remains unknown.Observational and cross-sectional study of 62 normotensive ADPKD patients with normal renal function and a group of 28 healthy controls. Renal volume, blood pressure, and renal (urinary albumin excretion), blood vessels (carotid intima media thickness and carotid-femoral pulse wave velocity), and cardiac (left ventricular mass index and diastolic dysfunction parameters) asymptomatic organ damage were determined and were considered as continuous variables. Correlations between renal volume and the other parameters were studied in the ADPKD population, and results were compared with the control group. Blood pressure values and asymptomatic organ damage were used to assess the cardiovascular risk according to renal volume tertiles.Even though in the normotensive range, ADPKD patients show higher blood pressure and major asymptomatic organ damage than healthy controls. Asymptomatic organ damage is not only related to blood pressure level but also to renal volume. Multivariate regression analysis shows that microalbuminuria is only associated with height adjusted renal volume (htTKV). An htTKV above 480 mL/m represents a 10 times higher prevalence of microalbuminuria (4.8% vs 50%, P < 0.001). Normotensive ADPKD patients from the 2nd tertile renal volume group (htTKV > 336 mL/m) show higher urinary albumin excretion, but the 3rd tertile htTKV (htTKV > 469 mL/m) group shows the worst cardiovascular risk profile.Normotensive ADPKD patients show in the early stages of the disease with slight increase in renal volume, higher cardiovascular risk than healthy controls. An htTKV above 468 mL/m is associated with the greatest increase in cardiovascular risk of normotensive ADPKD patients with normal renal function. Early strategies to slow the progression of the cardiovascular risk of these patients might be beneficial in their long-term cardiovascular survival., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Background: Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease., Methods: Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity., Results: In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients., Conclusions: Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Because of the high incidence of drug-related problems (DRPs) among hospitalized patients with cardiovascular diseases and their potential impact on morbidity and mortality, it is important to identify the most susceptible patients, who therefore require closer monitoring of drug therapy. Purpose: To identify the profile of patients at higher risk of developing at least one DRP during hospitalization in a cardiology ward. Method: We consecutively included all patients hospitalized in the cardiology ward of a teaching hospital in 2009. DRPs were identified through a computerized warning system designed by the pharmacy department and integrated into the electronic medical record. Results: A total of 964 admissions were included, and at least one DRP was detected in 29.8%. The variables associated with a higher risk of these events were polypharmacy (odds ratio [OR]=1.228; 95% confidence interval [CI]=1.153-1.308), female sex (OR=1.496; 95% CI=1.026-2.180), and first admission (OR=1.494; 95% CI=1.005-2.221). Conclusion: Monitoring patients through a computerized warning system allowed the detection of at least one DRP in one-third of the patients. Knowledge of the risk factors for developing these problems in patients admitted to hospital for cardiovascular problems helps in identifying the most susceptible patients. [ABSTRACT FROM AUTHOR]