The ACCORD trial will use 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 will be carried out in the Lipid Arm of ACCORD, in which the 5,800 subjects will all be treated with simvastatin and, in addition, be randomly assigned to receive either fenofibrate or placebo. The main ACCORD trial will measure only fasting blood samples for lipids, lipoprotein fractions, and apolipoproteins. In the proposed ancillary study, we will compare 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, we will 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 propose ancillary study will provide a unique opportunity to determine possible mechanisms whereby simvastatin plus fenofibrate therapy will be associated with reduced cardiovascular events in the overall ACCORD trail. 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.
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. ACCORD provides a unique opportunity to compare, in detail, 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.
| Ronsein, Graziella E; Reyes-Soffer, Gissette; He, Yi et al. (2016) Targeted Proteomics Identifies Paraoxonase/Arylesterase 1 (PON1) and Apolipoprotein Cs as Potential Risk Factors for Hypoalphalipoproteinemia in Diabetic Subjects Treated with Fenofibrate and Rosiglitazone. Mol Cell Proteomics 15:1083-93 |
| Reyes-Soffer, Gissette; Ngai, Colleen I; Lovato, Laura et al. (2013) Effect of combination therapy with fenofibrate and simvastatin on postprandial lipemia in the ACCORD lipid trial. Diabetes Care 36:422-8 |
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