CLINICAL STUDY: ATHEROSCLEROSIS
Irbesartan, an angiotensin type 1 receptor inhibitor, regulates markers of inflammation in patients with premature atherosclerosis
Sushant Navalkar, MD*,
Sampath Parthasarathy, PhD ,
Nalini Santanam, PhD and
Bobby V. Khan, MD, PhD*
* Department of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA
Gynecology/Obstetrics, Emory University School of Medicine, Atlanta, Georgia, USA
Manuscript received May 11, 2000;
revised manuscript received August 23, 2000,
accepted October 3, 2000.
Reprint requests and correspondence: Dr. Bobby V. Khan, Emory University School of Medicine, Department of Medicine, Division of Cardiology, 1639 Pierce Drive, WMB 319, Atlanta, Georgia 30322
mollykhan{at}hotmail.com
OBJECTIVES
This study assessed the role of angiotensin II type 1 (AT1) receptor antagonists on inflammatory mechanisms involved in atherogenesis. Specific inflammatory markers included solubilized tumor necrosis factor-alpha receptor II (sTNF- RII), vascular cell adhesion molecule-1 (VCAM-1) and superoxide. In addition, the AT1 receptor blocker irbesartan was evaluated for its ability to suppress these markers in individuals with atherosclerosis.
BACKGROUND
Mechanisms involved in the complex process of atherogenesis include alterations in the inflammatory responses. The use of compounds that suppress these responses may reduce the degree of damage seen in atherosclerosis.
METHODS
With a cross-sectional study design, 33 normotensive patients with stable coronary artery disease (CAD) were treated with irbesartan for a 24-week period. These patients were compared against a control population with no known coronary atherosclerosis. Marker levels were measured by enzyme-linked immunosorbent assay technique and lucigenin chemiluminescence assay and statistically evaluated by two-way repeated measures analysis of variance.
RESULTS
All patients with coronary artery disease had increased levels of inflammatory molecules over those of control patients. Treatment with irbesartan in these patients significantly reduced levels of inflammatory molecules measured. Soluble VCAM-1 levels were reduced by 36%; soluble TNF-alpha levels were reduced by 54% and superoxide level decreased by 52%. Maximal suppression of inflammatory markers by irbesartan therapy in patients with CAD was seen at 12 weeks.
CONCLUSIONS
The effect of irbesartan on each inflammatory marker is significant. Our results show that use of irbesartan may retard the inflammatory process seen in premature forms of atherosclerosis.
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Abbreviations and Acronyms
| | AT1 | = angiotensin II type 1 receptor | | AT2 | = angiotensin II type 2 receptor | | CABG | = coronary artery bypass graft | | CAD | = coronary artery disease | | ESR | = erythrocyte sedimentation rate | | HDL | = high density lipoproteins | | ox-LDL | = oxidized low density lipoproteins | | sTNF-IIR | = soluble tumor necrosis factor-alpha receptor type II | | TNF-RII | = tumor necrosis factor-alpha receptor II | | sVCAM | = soluble vascular cell adhesion molecule | | VCAM-1 | = vascular cell adhesion molecule-1 |
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