Resveratrol in Metabolic Syndrome: Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation
Condition: Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Syndrome
Study type: Interventional

Summary: 
      Metabolic syndrome is a group of risk factors that increase a patient's likelihood for heart
      attack, stroke and diabetes. Our research is aimed at understanding whether a drug,
      resveratrol, commonly found in grapes and red wine, would have any benefit in reducing risk
      factors in patients that have metabolic syndrome. Despite the use of aspirin and cholesterol
      reducing medications, patients with metabolic syndrome still often have sticky platelets and
      dysfunctional lipid profile. This is likely due to inflammation and high oxidative state. In
      animal studies, this drug has reduced platelet stickiness and reduced oxidative stress.
      However, the effects of this drug have not been researched in patients with metabolic
      syndrome.

      We are interested in studying whether the benefits of resveratrol described in animal models
      can be translated to patients with metabolic syndrome who display high markers of oxidative
      stress. We plan to give a short intervention of drug to patients and then determine if the
      drug successfully:

        1. Decreases the stickiness of platelets. This is important because sticky platelets are
           more likely to form clot and contribute to plaque formation.

        2. Reduce the circulating dysfunctional HDL. HDL and its protein and lipid constituents
           help to inhibit oxidation, inflammation, activation of the blood vessel wall,
           coagulation, and platelet aggregation. Dysfunctional HDL, as occurs in metabolic
           syndrome patients, cannot properly protect against atherosclerosis.
    

Detailed description: 
      Patients with metabolic syndrome are at increased risk of thrombotic complications, including
      myocardial infarction and cardiovascular death. A meta-analysis of the studies assessing
      cardiovascular risk in metabolic syndrome found a pooled relative risk for incident
      cardiovascular events and death of 1.78. This propensity for thrombotic vascular events is in
      the context of an increasing prevalence of metabolic syndrome, which in the 2003-2006 NHANES
      Survey was found in 34% of the US population over the age of 20.

      Two important contributors to the development of myocardial infarction and stroke are lipid
      rich atheromatous plaques and concomitant platelet aggregation in response to the fissuring
      of these plaques. A growing body of evidence implicates oxidative modification of lipoprotein
      lipids and apolipoproteins in the genesis of plaques. Platelet hyperactivity and the variable
      response to antiplatelet therapy are features of the metabolic syndrome. Oxidative
      modifications of LDL enhance activation of platelets, which themselves are oxidatively
      stressed. Myeloperoxidase (MPO) initiates lipid peroxidation leading to dysfunctional HDL
      production. Therefore, the hypotheses for the proposed investigations will address the
      effects of resveratrol on platelet hyperactivity and HDL protein modifications in patients
      with metabolic syndrome. Resveratrol, as predicted from its structure, is an electron rich
      molecule that can reduce free radicals. It has distinctive actions, however, that differ from
      compounds that are conventionally referred to as "anti-oxidants". It has particular potency
      as an inhibitor of radical formation by a number of peroxidases that likely participate in
      the pathophysiology of metabolic syndrome. These include MPO, the peroxidase site of
      prostaglandin H synthase-1 (PGHS-1; cyclooxygenase-1(COX-1)) and cytochrome c.

      We will test the hypothesis that:

        1. resveratrol reduces platelet activation in patients with metabolic syndrome. and

        2. that resveratrol reduces the oxidative modification of HDL proteins in patients with
           metabolic syndrome.
    

Intervention name(s): Resveratrol; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 1000mg tid; 1000mg tid placebo
Other intervention name(s): tid dosing; tid dosing
Intervention MeSH terms: Resveratrol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science