Journal
ATHEROSCLEROSIS
Volume 209, Issue 2, Pages 307-313Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2009.09.007
Keywords
Combination therapy; Atherosclerosis; Endothelial dysfunction; Insulin resistance; Risk factors
Funding
- Gil Medical Center, Gachon University, Incheon, Korea [2007-1]
- NCCAM, NIH
- Ministry of Education, Science & Technology (MoST), Republic of Korea [2007-1] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Large clinical trials demonstrate that control of blood pressure or hyperlipidemia reduces risk for cardiovascular events by similar to 30%. Factors that may further reduce remaining risk are not definitively established. One potential target is atherosclerosis, a crucial feature in the pathogenesis of cardiovascular diseases whose development is determined by multiple mechanism including complex interactions between endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidemia and the rennin-angiotensin-aldosterone system may contribute to development of atherosclerosis. Therefore, one appealing strategy for prevention or treatment of atherosclerosis may be to simultaneously address several risk factors with combination therapies that target multiple pathogenic mechanisms. Combination therapy with statins, peroxisome proliferators-activated receptor agonists, and rennin-angiotensin-aldosterone system blockers demonstrate additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors. Additive beneficial effects of combined therapy are mediated by both distinct and interrelated mechanisms, consistent with both pre-clinical and clinical investigations. Thus, combination therapy may be an important concept in developing more effective strategies to treat and prevent atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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