Usefulness of quinapril and irbesartan to improve the anti-inflammatory response of atorvastatin and aspirin in patients with coronary heart disease

摘要: A that inhibit the renin-angiotensin system (RAS), such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor blockers, have considerable benefit in hypertension heart failure.1–3 These compounds decrease hemodynamic stress, increase nitric oxide bioactivity, reduce pulse pressure.4–6 Recent longterm clinical studies indicated addition of an ACE inhibitor decreases morbidity mortality patients with stable coronary artery disease.7,8 Furthermore, we previously demonstrated treatment irbesartan early atherosclerosis markers inflammation may be sensitive to oxidative state vasculature.9,10 In present study, examine potential mechanisms by which either quinapril or can regulate vascular function already on a regimen aspirin atorvastatin therapy. • One hundred twelve subjects (64 men 48 women) disease systolic blood pressure 140 mm Hg were enrolled into study from several medical facilities metropolitan Atlanta, Georgia. All had been antianginal therapy, undergone bypass graft surgery, and/or percutaneous transluminal angioplasty 6 months before start study. considered their free any acute syndrome subjective symptoms chest pain for months. Patients started (10 40 mg/day) obtain target lowdensity lipoprotein cholesterol 100 mg/dl. Serum was collected stored at initiation (81 325 mg/day), equal number each group nitrates blockers. No patient taken AT1 beginning survey performed subject, following excluded: those necessity current smokers, previous myocardial infarction, ejection fraction 35% echocardiography ventriculography, diabetes glycosylated hemoglobin 8.5%, Hg, serum creatinine 2.2 mg/dl, active malignancy. The protocol approved research committee Emory University, all provided written, informed consent. placed average 3.7 (range 1.9 5.3) reach low-density Using randomized, open-label, crossover protocol, received 20 mg/day (Pfizer Inc., New York, York) (n 39), 150 (Bristol-Myers Squibb Sanofi-Synthelabo, Princeton, Jersey) 37), placebo 36) 24 weeks. samples 5 time intervals: (1) atorvastatin; (2) quinapril, irbesartan, placebo; (3) 4 weeks (4) 12 (5) placebo. Whole immunotyping fluorescence-activated cell sorting analysis using monoclonal antibody human CD11b receptor, protein binding sites very high affinity monocytes. obtained through Pharmingen/BD Biosciences (Lexington, Kentucky). flow cytometry analysis, changes monocyte expression determined described.5,10 plasma centrifuged 20°C. Enzyme-linked immunosorbent assays (ELISA) soluble interleukin-6 (sIL-6) sample triplicate (ELISA kits, Biosource International, Camarillo, California). Two microliters used analyses, ELISA described.9 levels sIL-6 read plate reader optical density 450 nm. data are presented mean value SEM. Comparisons within groups between 2-way variance. p 0.05 statistically significant. (Bonferroni correction applied; values related variance.) From Division Cardiology, University School Medicine, Georgia; Michigan, Ann Arbor, Michigan. Dr. B. Khan supported Medical Care Foundation, Georgia, Parthasarathy grant R01-HL34453 National Institutes Health/National Heart, Lung, Blood Institute, Bethesda, Maryland. Khan’s address is: 69 Jesse Hill Drive SE, C233, Georgia 30303. E-mail: bkhan@emory.edu. Manuscript July 8, 2002; revised manuscript accepted January 20, 2003.