Combination therapy for treatment or prevention of atherosclerosis: focus on the lipid-RAAS interaction

Atherosclerosis. 2010 Apr;209(2):307-13. doi: 10.1016/j.atherosclerosis.2009.09.007. Epub 2009 Sep 12.


Large clinical trials demonstrate that control of blood pressure or hyperlipidemia reduces risk for cardiovascular events by approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / physiopathology
  • Atherosclerosis / prevention & control*
  • Drug Therapy, Combination
  • Endothelium / physiopathology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Insulin Resistance
  • Peroxisome Proliferator-Activated Receptors / physiology
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology*
  • Risk Factors
  • Signal Transduction / drug effects
  • Vascular Diseases / drug therapy
  • Vascular Diseases / prevention & control


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Peroxisome Proliferator-Activated Receptors