Clinical trial NCT00329069: The Role of Atorvastatin on Monocyte Function in Patients With Coronary Artery Disease and Hypercholesterolemia
Official title: Vascular Endothelial Receptor Activity in Patients With Coronary Artery Disease on Medication With Statins
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Hypercholesterolemia
Monocyte Function
Keywords: statin
atorvastatin
hypercholesterolemia
coronary artery disease
monocyte
collateral formation
arteriogenesis
chemotaxis
migration
growth factors
vascular endothelial growth factor A
placenta growth factor 1
hepatocyte growth factor
monocyte chemotactic protein 1
Lead sponsor: University of Ulm
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2006-05-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The aim of this study is to determine, whether an intensified atorvastatin therapy can improve monocyte function in patients with coronary artery disease and hypercholesterolemia.

Detailed description: Hypercholesterolemia is one of the most important cardiovascular risk factors that significantly elevates the risk for the development and progression of arteriosclerotic diseases.

Statins such as atorvastatin have been shown to reduce atherogenic lipoprotein levels as well as cardiovascular morbidity and mortality in a large number of clinical trials. It is suggested that statins have- apart from their lipid-lowering properties- other pleiotropic effects that are responsible for their anti-atheroslerotic and and cardioprotective potential.

Monocytes are crucially involved in the process of arteriogenesis (i.e. the growth of preexisting arterioles). Monocyte chemotaxis can be stimulated with arteriogenic molecules such as vascular endothelial growth factor A (VEGF-A). In previous studies we could demonstrate that the VEGF-A- induced monocyte chemotaxis is severely impaired in hypercholesterolemic patients. This reduced response to VEGF seems to be associated with a decreased ability to form functional collaterals.

Therefore we hypothesize that an intensified therapy with atorvastatin 40 mg once a day can significantly improve monocyte function in patients with coronary artery disease and hypercholesterolemia compared to patients who are only treated with a placebo.

Eligibility criteria: Inclusion Criteria:

* coronary artery disease (angiographically proven)
* diagnosis of hypercholesterolemia (either LDL-C ≥ 4 mmol/l or already treated with lipid-lowering medication)

Exclusion Criteria:

* diabetes mellitus
* uncontrolled arterial hypertension (repeated BP ≥ 160/90 mmHg)
* smoking
* active infections
* acute coronary syndrome (\< 8 weeks)
* malignant diseases
* nephropathy

Primary outcomes:
measure: VEGF-A induced monocyte chemotaxis after 1-month treatment with atorvastatin 40 mg or a placebo once a day
measure: PlGF-1 induced monocyte chemotaxis after 1-month treatment with atorvastatin 40 mg or a placebo once a day
measure: HGF-induced monocyte chemotaxis after 1-month treatment with atorvastatin 40 mg or a placebo once a day
measure: MCP-1-induced monocyte chemotaxis after 1-month treatment with atorvastatin 40 mg or a placebo once a day
measure: VEGF-A+MCP-1-induced monocyte chemotaxis after 1-month treatment with atorvastatin 40 mg or a placebo once a day
Secondary outcomes:
measure: HGF+MCP-1-induced monocyte chemotaxis after 1-month treatment with atorvastatin 40 mg or a placebo once a day
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: University Hospital Ulm
Study officials:
affiliation: University of Ulm, Germay
name: Johannes Waltenberger, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Waltenberger J, Lange J, Kranz A. Vascular endothelial growth factor-A-induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus: A potential predictor for the individual capacity to develop collaterals. Circulation. 2000 Jul 11;102(2):185-90. doi: 10.1161/01.cir.102.2.185.