The C242T polymorphism of the p22phox component of NAD(P)H oxidase and vascular risk. Two case-control studies and a meta-analysis.

NAD(P)H oxidase is a prominent source of reactive oxygen species in the vasculature. Vascular NAD(P)H oxidase is comprised of several subunits, one of which, p22phox, is encoded by a gene exhibiting several allelic variants. Here the C(242)T nucleotide transition has been found to alter superoxide anion production and associated with an altered risk of coronary artery disease (CAD). We assessed the role of this variant in two case-control studies, and performed a meta-analysis of previously reported investigations relating it to vascular risk. Population I was comprised of 492 subjects with type 2 diabetes, with or without macrovascular disease, matched for age, sex, and duration of diabetes. Population II was comprised of 158 subjects with or without either CAD or cerebro-vascular disease, and matched for age, sex, smoking status, weight category and the presence of hypertension, dyslipidemia, and diabetes. Our findings were meta-analyzed together with additional studies retrieved from the literature. The C(242)T polymorphism distribution did not differ between cases and controls in populations I and II both at univariate and multivariate analyses, and this was confirmed in a meta-analysis with 11 previously published populations. The meta-analysis, however, suggested a protective role of the T allele on CAD as an end point in Asian populations. In conclusion, these data suggest a significant heterogeneity for a modulating role of the T allele in the C(242)T polymorphism of p22-phox for the occurrence of CAD across ethnicities, with the absence of a significant effect in Caucasians.

Awake blood pressure variability, inflammatory markers and target organ damage in newly diagnosed hypertension.

Increased blood pressure (BP) may stimulate vascular inflammation, which may itself induce pathological arterial changes. BP variability has been associated with target-organ damage and future cardiovascular complications. We hypothesized that BP variability, as derived from ambulatory BP monitoring, is related to inflammatory markers in newly diagnosed hypertension. Systolic (S) and diastolic (D) BP variabilities were assessed as the SD of 24-h pressure recordings in a cohort of 190 recently (<6 months) diagnosed, untreated hypertensive subjects. Target organ damage, assessed by measuring the carotid artery intima-media thickness, left ventricular mass index, and microalbuminuria, was related to plasma high-sensitivity C-reactive protein (hsCRP) and soluble (s) E-selectin, an endothelium-specific molecule. The patients' age (mean+/-SD) was 53.0+/-8.5 years, and 59% were male. Multivariable analysis identified awake SBP variability (95% confidence interval [CI]: 0.002-0.042, p=0.034) as an independent correlate of hsCRP and awake SBP (95% CI: 0.003-0.014, p=0.003), awake SBP variability (95% CI: 0.003-0.035, p=0.018), and microalbuminuria (95% CI: 0.075-0.280, p=0.001) as independent correlates of sE-selectin. When patients were divided into low and high awake SBP variability groups, age (p=0.001), hsCRP (p=0.0001), and sE-selectin (p=0.005) were significantly different in the two groups. After adjusting for age, these differences remained significant (p=0.022 and p=0.001 for hsCRP and sE-selectin, respectively). In recently diagnosed hypertensive subjects, hsCRP and sE-selectin levels are related to awake SBP variability. High SBP variability is likely associated with vascular inflammation in newly diagnosed hypertension, independent of SBP. (Hypertens Res 2008; 31: 2137-2146).

Awake systolic blood pressure variability correlates with target-organ damage in hypertensive subjects.

Growing evidence associates blood pressure (BP) variability with cardiovascular events in hypertensive patients. Here we tested the existence of a relationship between awake BP variability and target-organ damage in subjects referred for suspected hypertension. Systolic and diastolic BP variability were assessed as the standard deviation of the mean out of 24-hour, awake and asleep BP recordings in 180 untreated subjects, referred for suspected hypertension. Measurements were done at 15-minute intervals during daytime and 30-minute intervals during nighttime. Left ventricular mass index (by echo), intima-media thickness (by carotid ultrasonography), and microalbuminuria were assessed as indices of cardiac, vascular and renal damage, respectively. Intima-media thickness and left ventricular mass index progressively increased across tertiles of awake systolic BP variability (P for trend=0.001 and 0.003, respectively). Conversely, microalbuminuria was similar in the 3 tertiles (P=NS). Multivariable analysis identified age (P=0.0001), awake systolic BP (P=0.001), awake systolic BP variability (P=0.015) and diastolic BP load (P=0.01) as independent predictors of intima-media thickness; age (P=0.0001), male sex (P=0.012), awake systolic (P=0.0001) and diastolic BP (P=0.035), and awake systolic BP variability (P=0.028) as independent predictors of left ventricular mass index; awake systolic BP variability (P=0.01) and diastolic BP load (P=0.01) as independent predictors of microalbuminuria. Therefore, awake systolic BP variability by non-invasive ambulatory BP monitoring correlates with sub-clinical target-organ damage, independent of mean BP levels. Such relationship, found in subjects referred for recently suspected hypertension, likely appears early in the natural history of hypertension.

[Hemolysis following valve surgery]. / L'emolisi dopo chirurgia valvolare.

Hemolysis is a frequent complication of the implant of prosthetic valves, and is conditioned by a variety of factors, most of which related to the type of valve implanted and to the hemodynamic conditions following implantation. If sufficiently severe, it may lead to varying degrees of hemolytic anemia. The following laboratory tests are useful to diagnose and assess the severity of hemolytic anemia: hemoglobin levels; reticulocyte count; the demonstration of schistocytes on a blood smear; serum levels of lactic dehydrogenase, haptoglobin and iron. Treatment of hemolysis includes the supplementation of iron and folate when their deficiency is evident. Transfusions are necessary only in cases of severe anemia refractory to treatment. The use of beta-blockers appears to decrease the severity of hemolysis, likely because of the induction of bradycardia and of their negative inotropic effects. Some cases have been described of erythropoietin treatment for hemolytic anemia in these conditions, with favorable outcome. However erythropoietin use should currently be restricted to patients with severe hemolytic anemia in whom surgical repair or transfusions should be avoided or deferred. The recognition and the estimation of severity of hemolysis after valve implantation are important steps in the patients' follow-up and the premise for a rational treatment.