A targeted dual therapy approach to cardiovascularrisk reduction

摘要

Endothelial dysfunction is an early feature of the atherosclerotic disease process Damage to the endothelium leads to reduced nitric oxide (NO) bioavailability and facilitates vessel wall permeability to lipids and inflammatory cells Endothelial dysfunction is causally related to a variety of risk factors for coronary artery disease (CAD) including hyperlipidemia and hypertension; the strongest predictor of endothelial dysfunction is the total number of risk factors a person has Elevations in oxidized low-density lipoprotein cholesterol lead to endothelial dysfunction and multiple inflammatory processes such as foam cell formation and increased cytokine production Hypertension and associated metabolic disorders increase endothelial cell synthesis of collagen IV and fibronectin while reducing NO-dependent renal and cardiovascular relaxation Several agents known to restore endothelial function and NO bioavailability have been shown to have beneficial antiatherogenic activities and improve cardiovascular outcomes.These observations justify the need for global risk assessment and an integrated therapeutic approach to the treatment of atherosclerosis Future studies will determine whether combining agents that target different risk factors will have synergistic vascular benefits.