Comparative effects of diet and simvastatin on markers of thrombogenicity in patients with coronary artery disease

Abstract

We investigated the effects of statin on lipoproteins, vasomotor function, serologic markers of infl ammation, plaque stability, thrombogenicity, and the mechanism of regulation compared with the Step I Diet.  Sixty-three patients with angiographically documented coronary artery disease were enrolled in this study. All patients were in Canadian Cardiovascular Society class I or II. All patients were taught and placed on the American Heart Association Step I Diet throughout the study period. Data on baseline characteristics of study participants and brachial artery endothelium-dependent reactivity, as well as lipoprotein levels, markers of infl ammation, and plaque stability in blood have been reported previously and are listed in Tables 1 and 2. 1 The 2 groups were age- and gender-matched. Mean age of patients was 62 years, and 13 of 32 patients were men. The risk factors were hypertension (68% vs 72%; diet and placebo group vs diet and simvastatin group, respectively), diabetes (23% vs 25%), and current smoking (35% vs 31%). The proportion of medications were -adrenergic blockers (81% vs 81%), calcium channel blockers (48% vs 47%), angiotensin-converting enzyme inhibitors (23% vs 28%), long-acting nitrates (81% vs 84%), and aspirin (84% vs 88%). We administered diet placebo (n 31) and diet simvastatin 20 mg/day (n 32) in a randomized order for 14 weeks in patients with coronary artery disease using a singleblind prospective randomized design. The study was approved by the Gil Hospital Institutional Review Board, and all participants gave written informed consent. Blood samples for laboratory assays were obtained at approximately 8:00 A.M. following an overnight fast after pretreatment and simvastatin for 14 weeks. The samples were immediately coded so that investigators performing laboratory assays were blinded to subject identity or study sequence. Assays for lipoproteins and plasminogen activator inhibitor type-1 (PAI-1) antigens were performed as previously described. 2 Tumor necrosis factor (TNF)-, matrix metalloproteinase (MMP)-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, C-reactive protein (CRP), fi brinogen, and antithrombin III were measured in duplicates by an enzyme-linked immunosorbent assay (R & D Systems, Minneapolis, Minnesota) and rate nephelometry (IMMAGE; Beckman Coulter, Brea, California) as previously described. 3–5 Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) activity were measured in duplicate by actichrome assays (American Diagnostica, Greenwich, Connecticut) as previously described.5,6 All samples from the same patient (batch samples) were measured in blinded pairs on the same enzyme-linked immunosorbent assay kit to minimize run-to-run variability. The interassay and intraassay coeffi cients of variation were 6%. Data are expressed as mean SD or median (range 25% to 75%). After testing data for normality, we used Student’s paired t or Wilcoxon’s signed rank test to compare values between baseline and treatment