Atherosclerosis: current concepts of pathophysiology and pharmacological intervention based on trial outcomes.
Atherosclerosis related cardiovascular diseases are the leading cause of death in western societies. The clinical manifestations are chronic arterial obstructions or acute arterial occlusions in various vascular territories. The pathogenesis is only understood in part as yet. Arterial wall abnormalities, blood composition abnormalities and hemodynamic alterations are generally accepted to be causative (Virchow's triad). The key role is played by macrophages in the subendothelial space that are activated immunologically by oxidized LDL particles via the scavenger receptor pathway. Recently, endothelial dysfunction due to oxidative stress was identified as a priming factor in the course of the development of atherosclerotic plaques. Shear stress-induced microinjuries of the endothelium in hemodynamically compromised regions together with local coagulation activation associated with microinflammation of the plaque are currently thought to cause plaque rupture. This event is the reason for local clot formation and ultimate organ infarction. Treatment success is still insufficient, however some progress during the last decade is reflected by the improving outcome of atherosclerosis associated cardiovascular diseases. Evidence from clinical trials supports the efficacy of statins, antiplatelet agents, antihypertensive agents if necessary and omega-fatty acids in patients with overt atherosclerosis. The reduction of mortality achieved by those drugs amounts to: omega-fatty acids -21%, statins -16%, anti-platelet agents -14%, treatment of hypertension -13%. It is impossible to calculate the combined effect of these modalities since in each trial participants received co-medication containing agents tested in other trials.
von Baeyer
H
H
Dialysis Practice Berlin-Tiergarten, Berlin, Germany. HnsBay@aol.com
Hopfenmüller
W
W
Riedel
E
E
Affeld
K
K
D001161:Arteriosclerosis / Q000188:drug therapy* / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008297:Male; D016896:Treatment Outcome