Our results concerning correlations suggest that disturbances in BMI, body fat, and lipid metabolism may contribute to altered oxidative status in NAFLD, and insulin resistance may be related to decreased antioxidants in NAFLD as well as products of lipid peroxidation. However, although our results suggest interesting correlations, this different mostly "weak" relationships must be taken with caution.

Studies in animals show that fibroblast growth factor (FGF)-23 interferes with vascular reactivity induced by the nitric oxide (NO) system. To investigate the relationship between circulating FGF-23 levels and the response of forearm blood flow to ischemia (flow-mediated vasodilatation, FMD) and nitroglycerin, we tested 183 patients with stage 3-4 chronic kidney disease (CKD). None of them had cardiovascular complications or were taking drugs interfering with vascular function. Patients with FGF-23 levels above the median had significantly lower glomerular filtration rate, FMD, and fetuin-A levels (an anti-inflammatory molecule and potent inhibitor of calcification). They also had higher proteinuria and phosphate levels when compared to patients whose FGF-23 levels were below the median. The response to nitroglycerin was not different between the two groups. Multiple regression analysis showed that the relationship between FGF-23 and FMD was only modestly sensitive to adjustment for classical risk factors, biomarkers of bone mineral metabolism, high-sensitivity C-reactive protein, and homeostatic model assessment index. Adjustment for asymmetrical dimethyl arginine (ADMA) weakened the strength of this link; however, it remained highly significant. There was no independent association between FGF-23 and nitroglycerin. Thus, attenuation of FMD by ADMA suggests that this endogenous inhibitor of NO synthase may, in part, mediate the vascular effects of FGF-23 in patients with CKD.

Nebivolol, in contrast to metoprolol, improved oxidative stress, insulin sensitivity, decreased plasma soluble P-selectin and increased adiponectin levels in hypertensive patients. These beneficial effects of nebivolol may contribute to a reduction in cardiovascular risk in hypertensive patients.

Our results reveal an increased generation of reactive oxygen species and impairment of the antioxidant system in patients with hyperthyroidism, and particularly in patients with hypothyroidism. These findings indicate that thyroid hormones have a strong impact on oxidative stress and the antioxidant system.

Background: Magnesium is an essential ion for all living cells because over 300 enzymes require the presence of magnesium for their catalytic action. To date, no group has evaluated magnesium as a cardiovascular risk factor in chronic kidney disease (CKD) subjects, in which closely interrelated factors and potential confounders such as endothelial dysfunction, insulin resistance (the homeostasis model assessment (HOMA) index) and inflammation (expressed as serum C-reactive protein (CRP) levels) were also considered. Methods: Between March 2006 and December 2010, 283 CKD patients were followed up for time-to-event analysis until the occurrence of fatal or nonfatal cardiovascular events. Endothelium-dependent vasodilatation (flow-mediated dilatation; FMD) and endothelium-independent vasodilatation (nitroglycerin-mediated dilatation) of the brachial artery were assessed noninvasively using high-resolution ultrasound. Results: From the univariate analysis of FMD, it appears that a higher magnesium level is associated with less endothelial dysfunction. When a multivariate analysis was performed, magnesium and estimated glomerular filtration rates (eGFR) maintained a strong positive correlation with FMD, supporting the hypothesis that higher levels of magnesium may protect against endothelial damage. In univariate Cox proportional hazards models, FMD, magnesium, high sensitivity CRP, the HOMA index, eGFR, comorbid diabetes, hypertension, smoking status, systolic blood pressure, serum phosphate and intact parathormone emerged as significant predictors for cardiovascular outcomes. Kaplan-Meier curves showed significantly higher cardiovascular mortality rates in CKD patients whose serum magnesium levels were below 2.05 mg/dl. Conclusions: This observational cohort study showed that magnesium may be an independent predictor of future cardiovascular outcomes and is the first study demonstrating such a role in etiologically diagnosed CKD patients, across different stages.

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SummaryBackground and objectives Deterioration of kidney function impairs testosterone production, with hypogonadism being common in men with chronic kidney disease (CKD). In nonrenal populations, testosterone is suggested to participate in the atherosclerotic process. In male dialysis patients, we showed that low testosterone increases the risk of mortality. We here studied plausible links among testosterone levels, vascular derangements, and cardiovascular events in nondialysis CKD men.Design, setting, participants, & methods This was a cross-sectional analysis in which flow-mediated dilation (FMD) was assessed in 239 CKD male patients (stages 1 to 5; mean age 52 Ϯ 12 years), together with routine measurements, serum total and free testosterone, and follow-up for cardiovascular outcomes.Results Total and free testosterone levels decreased in parallel with the reduction of kidney function. Multiple regression analyses showed that total and free testosterone significantly and independently contributed to explain the variance of FMD. After a median follow-up of 31 months (range 8 to 35 months), 22 fatal and 50 nonfatal cardiovascular events occurred. In Cox analysis, the risk of cardiovascular events was reduced by 22% for each nanomole-per-liter increment of total testosterone. This reduced risk persisted after adjustment for age, renal function, diabetes mellitus, previous cardiovascular history, C-reactive protein, albumin, and FMD. The same was true for free testosterone concentrations. ConclusionsThe reduction in endogenous testosterone levels observed with progressive CKD was inversely associated with endothelial dysfunction and exacerbated the risk of future cardiovascular events in nondialysis male CKD patients.

SummaryBackground and objectives Both prolactin clearance and production are altered in CKD. In nonrenal populations, emerging evidence suggests that prolactin participates in the atherosclerotic process. Given the elevated cardiovascular risk of CKD, this study examined links between prolactinemia, vascular derangements, and outcomes.Design, setting, participants, & measurements This observational study was conducted in two cohorts: one with 457 nondialyzed CKD patients (mean age 52612 years; 229 men) with measurements of flow-mediated dilation (FMD) and carotid intima-media thickness and one with 173 hemodialysis patients (65612 years; 111 men) with measurements of pulse wave velocity (PWV). Patients were followed for cardiovascular events (n=146, nondialyzed cohort) or death (n=79, hemodialysis cohort).Results Prolactin levels increased along with reduced kidney function. Prolactin significantly and independently contributed to explain the variance of both FMD (in nondialyzed patients) and PWV (in hemodialysis patients), but not intima-media thickness. In Cox analyses, the risk of cardiovascular events in nondialyzed patients increased by 27% (hazard ratio [HR], 1.27; 95% confidence interval [95% CI], 1.17-1.38) for each 10 ng/ml increment of prolactin. Similarly, the risk for all-cause and cardiovascular mortality in hemodialysis patients increased by 12% (HR, 1.12; 95% CI, 1.06-1.17) and 15% (HR, 1.15; 95% CI, 1.08-1.21), respectively. This was true after multivariate adjustment for confounders and after adjustment within the purported causal pathway (FMD or PWV).Conclusions Prolactin levels directly associated with endothelial dysfunction/stiffness and with increased risk of cardiovascular events and mortality in two independent cohorts of CKD patients.