ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundIncreased superoxide anion production increases oxidative stress and reduces nitric oxide bioactivity in vascular disease states. NAD(P)H oxidase is an important source of superoxide in human blood vessels, and some studies suggest a possible association between polymorphisms in the NAD(P)H oxidaseCYBAgene and atherosclerosis; however, no functional data address this hypothesis. We examined the relationships between theCYBAC242T polymorphism and direct measurements of superoxide production in human blood vessels.Methods and ResultsVascular NAD(P)H oxidase activity was determined in human saphenous veins obtained from 110 patients with coronary artery disease and identified risk factors. Immunoblotting, reverse-transcription polymerase chain reaction, and DNA sequencing showed that p22phox protein, mRNA, and 242C/T allelic variants are expressed in human blood vessels. Vascular superoxide production, both basal and NADH-stimulated, was highly variable between patients, but the presence of theCYBA242T allele was associated with significantly reduced vascular NAD(P)H oxidase activity, independent of other clinical risk factors for atherosclerosis.ConclusionsAssociation of theCYBA242T allele with reduced NAD(P)H oxidase activity in human blood vessels suggests that genetic variation in NAD(P)H oxidase components may play a significant role in modulating superoxide production in human atherosclerosis.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundThis long-term, multicenter, randomized, double-blind, placebo-controlled, 2×2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients.Methods and ResultsThere were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, −0.07 versus −0.14 mm (P=0.004); minimum diameters, −0.09 versus −0.16 mm (P=0.0001); and percent diameter stenosis, 1.67% versus 3.83% (P=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events;P=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30;P=0.043) than their respective placebo patients.ConclusionsThis trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundChlamydia pneumoniaeis associated with coronary artery disease (CAD), although its causal role is uncertain. A small preliminary study reported a >50% reduction in ischemic events by azithromycin, an antibiotic effective againstC pneumoniae, in seropositive CAD patients. We tested this prospectively in a larger, randomized, double-blind study.Methods and ResultsCAD patients (n=302) seropositive toC pneumoniae(IgG titers ≥1:16) were randomized to placebo or azithromycin 500 mg/d for 3 days and then 500 mg/wk for 3 months. The primary clinical end point included cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction (MI), stroke, unstable angina, and unplanned coronary revascularization at 2 years. Treatment groups were balanced, and azithromycin was generally well tolerated. During the trial, 47 first primary events occurred (cardiovascular death, 9; resuscitated cardiac arrest, 1; MI, 11; stroke, 3; unstable angina, 4; and unplanned coronary revascularization, 19), with 22 events in the azithromycin group and 25 in the placebo group. There was no significant difference in the 1 primary end point between the 2 groups (hazard ratio for azithromycin, 0.89; 95% CI, 0.51 to 1.61;P=0.74). Events included 9 versus 7 occurring within 6 months and 13 versus 18 between 6 and 24 months in the azithromycin and placebo groups, respectively.ConclusionsThis study suggests that antibiotic therapy with azithromycin is not associated with marked early reductions (≥50%) in ischemic events as suggested by an initial published report. However, a clinically worthwhile benefit (ie, 20% to 30%) is still possible, although it may be delayed. Larger (several thousand patient), longer-term (≥3 to 5 years) antibiotic studies are therefore indicated.

ISSN:0009-7322    

出版商:OVID    

年代:2000

数据来源: OVID