Postprandial Lipemia and Endothelial Function in ACCORD- Ancillary to ACCORD
Condition: Atherosclerosis; Cardiovascular Diseases; Hypercholesterolemia; Heart Diseases
MeSH terms: Cardiovascular Diseases; Heart Diseases; Atherosclerosis; Hypercholesterolemia
Study type: Observational

Summary: 
      To compare the effects of statin therapy alone with statin plus fibrate therapy on several
      emerging risk factors for atherosclerotic cardiovascular disease in a representative subgroup
      of the ACCORD cohort that is being followed for cardiovascular endpoints.
    

Detailed description: 
      BACKGROUND:

      The National Heart, Lung, and Blood Institute-supported ACCORD trial uses two connected 2x2
      designs to test the efficacy of (a) optimal glucose control (HbA1c = 6.0%) versus standard
      control (HbA1c + 7.5%) in 10,000 patients with type 2 diabetes mellitus, (b) more intense
      systolic blood pressure control (120 mm Hg) versus less intense control (140 mm Hg) in 4,200
      of those patients, and (c) combined low density lipoprotein cholesterol lowering,
      triglyceride lowering, and high density lipoprotein cholesterol raising versus only low
      density lipoprotein cholesterol lowering in 5,800 of those patients. The primary outcome for
      the overall ACCORD trial is a combination of non-fatal myocardial infarction, non-fatal
      stroke, and cardiovascular death. The comparison of lipid-altering therapies is carried out
      in the Lipid Arm of ACCORD, in which the 5,800 subjects are treated with simvastatin and, in
      addition, are randomly assigned to receive either fenofibrate or placebo. The main ACCORD
      trial measures only fasting blood samples for lipids, lipoprotein fractions, and
      apolipoproteins. The ancillary study compares the effects of simvastatin plus fenofibrate
      with the effects of simvastatin alone on postprandial lipemia in 250 ACCORD patients at 4
      sites in the Northeast Network.

      The study is in response to an initiative on Ancillary Studies in Heart, Lung, and Blood
      Disease Trials released in June, 2000.

      DESIGN NARRATIVE:

      The ancillary study compares the effects of simvastatin plus fenofibrate with the effects of
      simvastatin alone on postprandial lipemia in 250 ACCORD patients at 4 sites in the Northeast
      Network. In addition, the study compare the effects of the two treatment strategies on
      baseline and postprandial endothelial function, and on markers of coagulation, endothelial
      function, and oxidative stress. The ancillary study provides a unique opportunity to
      determine possible mechanisms whereby simvastatin plus fenofibrate therapy may be associated
      with reduced cardiovascular events in the overall ACCORD trial. The study is divided into
      three specific aims. Specific Aim A: To carry out high fat load studies of postprandial
      lipemia in patients who are participating in the Lipid Arm of the ACCORD trial and compare
      postprandial excursions of triglycerides, triglyceride-rich lipoproteins, retinyl palmitate,
      and remnant lipoprotein cholesterol in patients receiving fenofibrate plus simvastatin with
      those postprandial excursions in patients receiving only simvastatin. Specific Aim B: To
      determine brachial artery dilatation in response to increased blood flow post- forearm
      ischemia just prior to, and five hours after, ingestion of a high fat load in the two patient
      groups.and Specific Aim C: To determine baseline levels of PAI-1, fibrinogen and factor VII,
      and postprandial excursions of factor VII, sVCAM-1, sICAM-1, and sE-selectin in the two
      patient groups.
    

Time perspective: Retrospective