Background: Heart failure has been associated with impaired endothelial function, increased inflammatory process and elevated oxidative stress status. Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and/or advanced atherosclerosis. Aim: To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a) and vascular cells adhesion molecule (sVCAM-1) in patients with ischemic heart failure. Methods: Thirty-eight male patients with ischemic cardiomyopathy were randomly divided into three groups and received either atorvastatin 10 mg/day (n = 14), a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day (n = 12), or no statin or antioxidant treatment (n = 12, controls) for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration, respectively. Results: RH% was significantly improved in both the atorvastatin-treated ( p < 0.01) and atorvastatin plus vitamin E groups ( p < 0.05), but the increase was significantly higher in the atorvastatin-treated group ( p < 0.05). Serum levels of IL-6, TNF-a and sVCAM-1 were decreased in the atorvastatin-treated group ( p < 0.05 for all), but remained unaffected in the other two groups ( p = NS for all). Conclusions: Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure, an effect partly depressed by vitamin E.

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The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces superoxide, thus regulating redox state in the vessel wall. Three single-nucleotide polymorphisms (SNPs; À930A/G, A640G and C242T) of the p22 phox subunit have been associated with hypertension; however, their role in peripheral and central pressures in normotensive individuals has not been addressed. A total of 210 healthy, normotensive individuals were studied. Genotypes for the À930A/G, A640G and C242T polymorphisms were determined by polymerase chain reaction. Peripheral pressures were measured by mercury sphygmomanometer and aortic pressures by a validated device using applanation tonometry. Both peripheral and central pressures differed across À930A/G genotypes. G allele carriers showed higher levels of peripheral systolic blood pressure (PSBP; AA: 113±12, GG/AG: 119±12 mm Hg; Po0.01) and peripheral diastolic blood pressure (AA: 70±9, GG/AG: 73±10 mm Hg; Po0.05). Regarding central pressures, AA homozygotes had lower central systolic blood pressure (CSBP; AA: 103±12, GG/AG: 108 ± 12 mm Hg; Po0.01) and central diastolic blood pressure (AA: 71 ± 9, GG/AG: 74 ± 10 mm Hg; Po0.05). In multiple linear regression analysis, presence of the G allele (AG or GG) independently predicted CSBP. Blood pressure levels did not differ across A640G and C242T genotypes. The À930A/G polymorphism of p22 phox is a determinant of peripheral and central pressures in normotensive individuals. The G allele is associated with higher blood pressure in the brachial artery, as well as in the aorta. These findings further elucidate the role of this polymorphism in the regulation of blood pressure. In contrast, the A640G and C242T SNPs do not influence peripheral and central pressures in normotensives.

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This study aimed at evaluating the changes in platelet-activating factor (PAF) and its metabolic enzymes over a 6-week follow-up period in patients with newly diagnosed heart failure ([HF] n = 12) compared with age-, sex-, and BMI-matched apparently healthy volunteers (n = 10). The PAF, its key biosynthetic enzymes (lyso-PAF acetyltransferase [lyso-PAF-AT] and dithiothreitol [DTT]-insensitive CDP choline: 1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase [PAF-CPT]), and its catabolic isoenzymes (PAF-acetylhydrolase [PAF-AH] and lipoprotein-associated phospholipase A2 [Lp-PLA2]) were measured in serum and leukocytes of participants. At baseline, patients with HF had lower median activities of lyso-PAF-AT (P < .001) and PAF-CPT (P = .07) in parallel with PAF levels (P = .05) and higher activities of PAF-AH (P = .02) and Lp-PLA2 (P < .001) than controls. At follow-up, PAF-CPT and PAF levels marginally increased (P = .1), lyso-PAF-AT (P < .001) remained downregulated, while PAF-AH (P = .004) and Lp-PLA2 (P < .001) remained elevated compared with the controls. Newly diagnosed patients with HF under drug treatment have an affected profile of PAF biosynthetic enzymes and especially lyso-PAF-AT.