Title
Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia
Study of Lipoprotein Subfractions, Inflammation, Oxidative Stress and Endothelial Function After Treatment With Simvastatin and Ezetimibe Administered Alone and in Combination in Hyperlipidemic Patients
Phase
N/ALead Sponsor
University of ValenciaStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
DyslipidemiaIntervention/Treatment
simvastatin ezetimibe ...Study Participants
42Coadministration of drugs is common in the pharmacologic treatment of dyslipidemia, with statins and ezetimibe generally constituting the medication of choice. By acting at different levels, the combination of these drugs allows the therapeutic objective to be achieved. However, it is not known how these drugs qualitatively affect the composition of lipoprotein subfractions, which differ in size and atherogenic potential. The investigators set out to evaluate this effect as well as their effects on inflammatory, oxidative stress and endothelial function parameters.
The study consisted of a randomised parallel trial and took place during a period of 2 months. A total of 42 hyperlipidemic patients were randomly assigned to one of 2 groups: one received simvastatin (40 mg/day) and the other received ezetimibe (10 mg/day) for 4 weeks, after which both groups were administered combined therapy for an additional 4-week period. Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
simvastatin (40 mg/day) for 4 weeks
ezetimibe (10 mg/day) for 4 weeks
combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Hyperlipidemic patients received simvastatin (40 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period. Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
Hyperlipidemic patients received ezetimibe (10 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period. Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
Inclusion Criteria: LDL cholesterol concentration of between 160-190 mg/dl in patients with less than 2 cardiovascular risk factors LDL concentration of between 130-160 mg/dl in patients that presented 2 or more cardiovascular risk factors. Cardiovascular risk factors were defined as: age (≥ 45 years in men and ≥55 years in women), a smoking habit, hypertension (≥140/90 mmHg), diabetes mellitus, a high-density lipoprotein (HDL) cholesterol concentration of ≤ 40mg/dl, and a family history of cardiovascular disease. Exclusion Criteria: Triglyceride concentration > 400 mg/dl Diabetes Mellitus Kidney, liver, or thyroid disease
| Event Type | Organ System | Event Term |
|---|
LDL subfractions were separated by high-resolution polyacrylamide gel tubes using the Lipoprint® system. The LDL electrophoretic profile allows 2 patterns to be defined: pattern A or large and buoyant LDL, and pattern non-A or small and dense LDL.
Triglyceride concentration were measured by enzymatic assay
Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the method of Friedewald.
Levels of apolipoprotein B were determined by inmunonephelometry
High-density lipoprotein cholesterol (HDLc) concentration was measured using a direct method
Non-HDLc concentration was obtained by calculating the difference between total cholesterol and HDLc
Total cholesterol concentration was measured by enzymatic assay
Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy. Leukocyte rolling was estimated as the number of leukocytes rolling over 100 μm2 of the endothelial monolayer during a 1-min period.
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy. Adhesion was evaluated by counting the number of polymorphonuclear cells that maintained stable contact with human umbilical vein endothelial cells (HUVEC) for 30 seconds.
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.The rolling velocity in the field of focus was determined by measuring the time required by 20 consecutive leukocytes to cover a distance of 100 μm.
The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system
The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system
E-selectin was evaluated in serum by Luminex® 200™ system
Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay
Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system
Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system
Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode
Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques
Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques
