Atorvastatin, Aspirin, Oxidative Stress, Coagulation and Platelet Activation Indexes

• Status: Unknown status
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary and secondary prevention trials with statins, as well as with antiplatelet, clearly demonstrated that these drugs are able to reduce cardiovascular events. Even if the principal mechanism of action of statins is to lower cholesterol, other effects, the so-called pleiotropic effects, have been considered as adjunctive properties potentially accounting for the anti-atherosclerotic effect of statins.

Inhibition of oxidative stress may be considered an intriguing pleiotropic effect in view of the fact that oxidative stress is thought to be a key event in the initiation and progression of atherosclerotic disease. Reduction of several markers of oxidative stress including isoprostanes, 8-hydroxydeoxyguanosine (8-OHdG), and nitrotyrosine have been observed after statin treatment. NADPH oxidase is among the most important sources of reactive oxygen species involved in atherosclerotic disease. The investigators developed an ELISA to evaluate serum levels of soluble-gp91phox, the catalytic core of phagocyte NADPH oxidase. Recently the investigators showed that statins (30 days treatment) exert an antioxidant effect via inhibition of soluble gp91phox expression.

The exact mechanism by which atorvastatin reduces NADPH oxidase, however, is unclear. Recent study showed that statin treatment inhibits leukocyte ROCK activity, a protein kinase implicated in the activation of NADPH oxidase, with a mechanism that seems to be independent from lowering cholesterol. To further study the mechanism(s) implicate in gp91phox downregulation by statin the investigators planned the present study in patients with high risk of vascular events such as hypercholesterolemic and Type 2 Diabetes mellitus patients.

In addition the investigators want to evaluate the synergistic role of atorvastatin with aspirin treatment.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Roma La Sapienza
• Treatments: Aspirin; Atorvastatin; Atorvastatin Calcium

Criteria

For Hypercholesterolemic patients:

Inclusion Criteria:

• Patients with polygenic hypercholesterolemia (LDL-C > 160 mg/dl)

• Males and Females

• White race

• Sign of the informed consent

Exclusion Criteria:

• Liver insufficiency

• Serious renal disorders

• Diabetes mellitus

• Arterial hypertension

• History or evidence of previous myocardial infarction or other atherothrombotic diseases

• Any autoimmune diseases

• Cancer

• Present or recent infections

• Patients were taking nonsteroidal antiinflammatory drugs, drugs interfering with cholesterol metabolism, or vitamin supplements

For T2 Diabetic patients:

Inclusion Criteria:

• Patients with T2DM diagnosed according to the American Diabetes Association definition

• Treatment with 100 mg/day aspirin from at least 30 days

• Males and Females

• White race

• Sign of the informed consent

Exclusion Criteria:

• recent history (< 3 months) of acute vascular events

• clinical diagnosis of type 1 DM

• serum creatinine level greater than 2.5 mg/dl

• active infection or malignancy

• cardiac arrhythmia or congestive heart failure

• use of non-steroidal anti-inflammatory drugs, vitamin supplements, or other antiplatelet drugs such as clopidogrel in the previous 30 days