Systemic Inflammation: The Central Factor in Pathogenesis of Unstable Angina
To the Editor:
In their recent review, Hamm and Braunwald1 stated that inflammation is an integral component in the pathogenesis of unstable angina. However, a detailed explanation is missing. The current literature is also unclear about the role of different components of inflammation in the pathogenesis of acute coronary syndromes (ACS).2 Being able to explain only half of the ACS, the localized acute vessel wall inflammation leading to plaque rupture fails to generate a tenable uniform model for the pathogenesis of ACS. Systemic inflammatory responses involving the activation of circulating lymphocytes, monocytes, and neutrophils (different from plaque inflammation), the cytokine responses, and the elevation of markers of systemic inflammation such as C-reactive protein have recently emerged as important components of ACS.3 Thus, there are 2 separate (and possibly interconnected) acute inflammatory components associated with ACS, systemic inflammation and vessel wall inflammation.
The available literature suggests that the acute systemic cellular responses and the elevation of the markers of systemic inflammation in ACS are primary responses rather than byproducts of plaque rupture, thrombosis, or myocardial necrosis.3 In addition, the involvement of coronary vasculature in ACS is diffuse rather than localized to the plaques.3 Hence, we propose that the systemic inflammation triggered by unknown factors is the primary event and the central component in the pathogenesis of ACS. The systemic inflammation then migrates to the vessel wall and triggers and/or enhances localized inflammatory processes at the diseased substrate coronary segments. At an unstable plaque, this results in rupture. Similar to the concept Russel Ross evoked in atherosclerosis,4 in the normal-appearing coronary segments, the underlying endothelial dysfunction/injury may be acting as the diseased substrate for the systemic inflammation. The augmented intimal inflammatory processes over dysfunctional or injured endothelium and ruptured plaques result in activation of procoagulant cells. This triggers thrombotic and vaso-occlusive mechanisms. Systemic inflammation has also been closely correlated with the procoagulant milieu associated with ACS.3
A disruption of the endothelium during angioplasty augments the existing systemic inflammation (C-reactive protein levels) in patients with unstable angina.3 Thus, a recurrent reciprocal activation of intimal and systemic inflammation could be initiated (hence, the stuttering progression of ACS). The effectiveness of regulatory mechanisms in containing this reciprocating cycle of immune responses determines the further progression and clinical outcome.
- Copyright © 2001 by American Heart Association