Enhanced Inflammatory Response in Patients with Preinfarction Unstable Angina
ABSTRACT & Commentary
Synopsis: Individuals who have an enhanced acute-phase response to stimulation by oxidized LDL, chronic infection, or inflammatory stimuli may be at increased risk for unstable angina or evolution to MI.
Source: Liuzzo G, et al. J Am Coll Cardiol 1999;34: 1696-1703.
Liuzzo and associates have made pioneering observations of inflammatory markers in subjects with acute myocardial infarction (MI) and unstable angina. In this report, they examine whether there are differences in the inflammatory milieu in individuals who develop MI with or without angina pectoris in the weeks prior to the MI. A cohort of 36 individuals who presented with chest pain consistent with acute MI, and initially normal enzymes were followed with serial determinations of C-reactive protein (CRP) and serum amyloid A protein (SAA) as well as interleukin-6 and troponin T measurements. Twenty patients had an "unheralded MI" (group 1) (e.g., chest pain was the initial manifestation of coronary disease or there was a history of stable angina without worsening prior to the acute event). Another 16 patients had symptoms of severe unstable angina (Braunwald Class IIIB) in the preceding seven days (range 2-18 d, average 10 d) prior to admission (group 2). The results indicated that the patients presenting with unstable angina prior to the MI had much higher levels of CRP and SAA immediately before the actual event, and "strikingly higher peaks of IL-6, CRP, and SAA despite similar infarct size and clinical signs of reperfusion." In contradistinction, only 45% of the unheralded MI group had baseline elevated CRP; CRP and SAA were normal in 11 subjects. CRP or SAA was elevated in all unstable angina patients (P = 0.002 vs group 1); IL-6 levels were much higher than those in group 2. Liuzzo et al conclude that the group 2 unstable angina patients had a "strikingly higher acute phase response" than the group 1 patients, as indicated by major increases in all markers of inflammation. In that they also had much higher levels of SAA and CRP prior to the infarction, and higher peak levels following the infarct, an inflammatory state with monocyte activation was apparently ongoing at the time these individuals presented.
Elevation of CRP in similar patients has been shown to be associated with increased risk of major cardiac coronary events. Liuzzo et al speculate that the pre-infarction patients may be "more responsive . . . to the inflammatory stimuli caused by myocardial necrosis and reperfusion, and that the elevated acute phase reactants are markers of such hyper-responsiveness." They suggest that monocytes and granulocytes may have been activated to produce more cytokines and oxygenfree radicals. Liuzzo et al believe that hyper-responsiveness is key in the group 2 patients, in that the CRP and SAA levels, normalized for peak CK, were much higher in the unstable vs. unheralded populations. Liuzzo et al hypothesize that individuals who have an enhanced acute-phase response to stimulation by oxidized LDL, chronic infection, inflammatory stimuli, or other may be at increased risk for unstable angina and evolution to MI. The factors responsible for progression of unstable angina to MI may be different than in those triggering an unheralded infarct. Thus, potential therapeutic decisions might be different in some subjects if these data are confirmed by other studies.
Inflammatory markers that may be elevated in acute coronary syndromes include:
a. C-reactive protein.
b. serum amyloid A protein.
c. interleukin-6.
d. All of the above
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