CLINICAL STUDY
Systemic inflammation in unstable angina is the result of myocardial necrosis
Michael R. Cusack, MB, MRCP*,
Michael S. Marber, PhD, FACC*,
Pier D. Lambiase, BA, MRCP*,
Clifford A. Bucknall, MD, FRCP* and
Simon R. Redwood, MD, FACC*,*
* Department of Cardiology, Rayne Institute, St. Thomas’ Hospital, London, United Kingdom
Manuscript received October 24, 2001;
revised manuscript received March 11, 2002,
accepted April 1, 2002.
* Reprint requests and correspondence: Dr. Simon Redwood, Department of Cardiology, Rayne Institute, KCL, St. Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom.
simon.redwood{at}gstt.sthames.nhs.uk
OBJECTIVES: We investigated whether the source of the acute phase response in unstable angina (UA) lay within the culprit coronary plaque or distal myocardium.
BACKROUND: An inflammatory response is an important component of the acute coronary syndromes. However, its origin and mechanism remain unclear.
METHODS: In 94 stable patients undergoing coronary angiography, the relationship between systemic levels of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and C-reactive protein (CRP) and extent of atherosclerosis was studied. The temporal relationship between these markers and troponin T (TnT) was determined in 91 patients with UA. Cytokine levels were measured in the aortic root and coronary sinus of 36 unstable patients.
RESULTS: There was no relationship found between stable coronary atherosclerosis and inflammatory marker levels. Compared with this group, admission levels of IL-6 (3.6 ± 0.3 ng/ml vs. 10.7 ± 1.7 ng/ml, p < 0.05) and CRP (2.3 ± 0.1 mg/l vs. 4.6 ± 0.6 mg/l, p < 0.05) were elevated in patients with UA. In this group, IL-6 and CRP remained elevated in those who subsequently experienced major adverse cardiac events. This inflammatory response occurred in parallel to the appearance of TnT. Both TNF-alpha (19.2 ± 3.4 ng/ml vs. 17.1 ± 3.3 ng/ml, p < 0.001) and IL-6 (10.3 ± 1.4 ng/ml vs. 7.7 ± 1.1 ng/ml, p < 0.01) were elevated in the coronary sinus compared with aortic root in patients with UA. This was principally observed in those who were TnT positive. There was no cytokine gradient across the culprit plaque.
CONCLUSIONS: There is an intracardiac inflammatory response in UA that appears to be the result of low-grade myocardial necrosis. The ruptured plaque does not appear to contribute to the acute phase response.
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Abbreviations and Acronyms
| | CRP | | C-reactive protein | | IL | | interleukin | | MACE | | major adverse cardiac event | | MI | | myocardial infarction | | PTCA | | percutaneous transluminal coronary angioplasty | | TNF | | tumor necrosis factor | | TnT | | troponin T | | UA | | unstable angina |
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