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Background We aimed to determine if immune-unreactive albumin excretion (IURAE) is associated with cardiovascular (CV) events in a representative sample of a general population from Spain. Methods We included 1297 subjects (mean age ± standard error 48.0 ± 0.2 years, 48% females), who participated in the Hortega Follow-Up Study. The primary endpoint was incidence of fatal and non-fatal CV events. Urinary albumin excretion (UAE) was measured in spot voided urine, frozen at –80°C, by immunonephelometry [immune-reactive albumin excretion (IRAE)] and by high-performance liquid chromatography (HPLC) [total albumin excretion (AE)]. IURAE was calculated as the difference between HPLC measurements and IRAE. We estimated fully adjusted hazard ratios (HRs) of CV incidence by Cox regression for IRAE, IURAE and total AE. Results After an average at-risk follow-up of 13 years, we observed 172 CV events. urinary albumin to creatinine ratio (UACR) of ≥30 mg/g assessed by IRAE, IURAE or total AE concentrations was observed in 74, 273 and 417 participants, respectively. Among discordant pairs, there were 49 events in those classified as micro- and macroalbuminuric by IURAE, but normoalbuminuric by IRAE. Only the IRAE was a significant independent factor for the incidence of CV events [HR (95% confidence interval) 1.15 (1.04–1.27)]. The association of UAE with CV events was mainly driven by heart failure (HF) [HR 1.33 (1.15–1.55) for IRAE; HR 1.38 (1.06–1.79) for IURAE; HR 1.62 (1.22–2.13) for total AE]. Those subjects who were micro- and macroalbuminuric by both IRAE and IURAE had a significant increase in risk for any CV event, and especially for HF. Conclusions IRAE, IURAE and AE were associated with an increased risk for CV events, but IRAE offered better prognostic assessment. [ABSTRACT FROM AUTHOR]

Untreated hypertensive patients show increased oxidative stress and decreased antioxidant enzyme activity in mononuclear cells. Therefore, the objective of this study was to determine whether or not the low antioxidant enzyme activity observed in mononuclear cells of hypertensive subjects is in part dependent on a defective activity of antioxidant mechanisms. Activity and mRNA level of antioxidant enzymes, CuZn- and Mn-superoxide dismutases, catalase, glutathione peroxidase type 1, and glutathione reductase were simultaneously measured in mononuclear cells of controls (n = 38) and hypertensive subjects (n = 35), in the absence of and during antihypertensive treatment. An increase in oxidative stress and a decrease in the activity of cytoplasmic enzymes were observed in untreated hypertensive patients. Concurrently, CuZn-superoxide dismutase and glutathione reductase mRNA levels were significantly reduced, and glutathione peroxidase type 1 mRNA was slightly reduced. In contrast, increased activity and mRNA levels of the mitochondrial Mn-superoxide dismutase were observed. Antihypertensive treatment, nonpharmacologic with or without a drug regimen of β-blocker or angiotensin AT1 receptor blocker was administered for a 3-month period. Afterward, after the improvement in oxidative stress during treatment, a recovery of the cytoplasmic antioxidant enzymatic activity and a more profound decrease in mRNA levels were observed for CuZn-superoxide dismutase, glutathione peroxidase type 1, and glutathione reductase. Meanwhile mitochondrial enzymatic activity decreased, as did the mRNA level. The inadequate response of the main cytoplasmatic antioxidant systems, as well as of the enzymes participating in the maintenance of glutathione levels, may contribute to the vulnerability of hypertensives to oxidative stress. [Copyright &y& Elsevier]

The objective of the study was to evaluate oxidative stress (OS) status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT) with and without metabolic syndrome, familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) and activation of both pro-oxidant enzyme (NAPDH oxidase components) and AGTR1 genes, as well as antioxidant enzyme genes (CuZn-SOD, CAT, GPX1, GSR, GSS and TXN) were measured in mononuclear cells of controls (n = 20) and patients (n = 90) by assessing mRNA levels. Activity of some of these antioxidant enzymes was also tested. An increase in OS and pro-oxidant gene mRNA values was observed in patients compared to controls. The hypertensive group showed not only the highest OS values, but also the highest pro-oxidant activation compared to those observed in the other groups. In addition, in HT a significantly reduced antioxidant activity and mRNA induction of antioxidant genes were found when compared to controls and the other groups. In FH and FCH, the activation of pro-oxidant enzymes was also higher and antioxidant ones lower than in the control group, although it did not reach the values obtained in hypertensives. The thioredoxin system was more activated in patients as compared to controls, and the highest levels were in hypertensives. The increased oxidative status in the presence of cardiovascular risk factors is a consequence of both the activation of pro-oxidant mechanisms and the reduction of the antioxidant ones. The altered response of the main cytoplasmic antioxidant systems largely contributes to OS despite the apparent attempt of the thioredoxin system to control it. [ABSTRACT FROM AUTHOR]