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A crucial point in understanding the clinical and pathophysiologic meaning of C-reactive protein (CRP) elevation in acute coronary syndromes (ACS) is whether CRP release is predominantly a response to even small amounts of myocardial necrosis, for which troponin is a sensitive and specific marker, or is an independent indicator of the inflammatory process occurring in that clinical condition. Whereas troponin is a good predictor of both mortality and myocardial infarction (MI), although the highest values are associated with a decreased probability of MI, CRP predicts mortality but has no relation with the early or late occurrence of MI. The large variability of CRP values in ACS may depend on the different response of this inflammation marker to various stimuli, some patients being particularly hyperresponsive, especially those with elevated CRP values at baseline. We hypothesize that myonecrosis, as detected by troponin increases, would represent the strongest stimulus for CRP increase in ACS, causing in some patients, especially those with already-elevated CRP values at baseline, a disproportionate increase of this marker. Accordingly, the highest CRP values during ACS are likely to be observed in patients with already-elevated CRP values at baseline (which would increase the probability of having death and MI in the follow-up) and the highest troponin values (which would increase the probability of death in the follow-up, but not of subsequent MI). This hypothesis would explain why high CRP levels in unstable coronary disease are good predictors of death, but not of MI.

OBJECTIVES The purpose of this study was to evaluate benzodiazepine receptor expression on leukocytes from patients with symptomatic or silent myocardial ischemia. BACKGROUND Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Pain can be effectively controlled by various endogenous mechanisms. Benzodiazepines and their receptors play key roles in pain, in interactions with peptide opioids, in inflammation and in the response to stress. METHODS The study group consisted of 57 patients with reproducible exercise-induced myocardial ischemia. The presence of a constant behavior in the anginal pain perception during both exercise-induced ischemia and daily life was the most important inclusion criterion. Venous blood samples were taken from all patients to evaluate the expression of peripheral benzodiazepine receptors by flow cytometry. The study cohort was classified into two groups: 24 patients who had anginal pain both at home and during the exercise stress test and 33 patients who were asymptomatic during both daily life and exercise-induced ischemia. RESULTS Flow cytometry analysis showed increased expression of peripheral benzodiazepine receptors on all types of leukocytes in the asymptomatic patients. The difference was statistically significant for lymphocytes (p < 0.005), monocytes (p < 0.001) and granulocytes (p < 0.001). CONCLUSIONS These data show that expression of peripheral benzodiazepine receptors was higher in patients with silent myocardial ischemia than in symptomatic patients.

Objectives.This study sought to evaluate the relation, if any, between clinical and angiographic findings in patients with unstable angina and monocyte and neutrophil CD11b/CD18 receptor density. The expression of HLA-DR molecules on T lymphocytes, an index of activation of these cells, was also investigated.Background.Although activation of neutrophils and monocytes has recently been shown in unstable angina, no studies have correlated activation indexes with clinical and angiographic features of patients with this clinical condition.Methods.Sixty patients underwent diagnostic coronary arteriography and simultaneous blood sampling from the aorta and coronary sinus before injection of contrast medium. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytometry using monoclonal antibodies tagged with fluorescent markers.Results.In 38 patients with unstable angina, neutrophils and monocytes showed a significantly higher expression of CD11b/ CD18 adhesion receptors in coronary sinus than aortic blood (p < 0.0001 and p < 0.001, respectively). When these patients were analyzed according to clinical characteristics or angiographic findings, no difference in CD11b/CD18 receptor expression in coronary sinus blood was found between the various subgroups, except for patients with at least one episode of chest pain at rest within 48 h of coronary arteriography and a higher neutrophil adhesion molecule density than patients who remained asymptomatic (p = 0.04). Lymphocytes in patients with stable and unstable angina showed a similar percent expression of CD2/ CD19 and CD3/HLA-DR antigens, with no difference between aortic and coronary sinus blood.Conclusions.These results in a larger cohort confirm previous data that neutrophil and monocyte CD11b/CD18 adhesion molecules show a higher expression in the coronary sinus blood of patients with unstable angina. Among clinical and angiographic findings in patients with unstable angina, only the occurrence of chest pain within 48 h of coronary angiography was related to significantly higher values of neutrophil fluorescence intensity, suggesting that the degree of neutrophil activation is related to the proximity of rest angina episodes to blood sampling. Finally, our data do not support the concept of systemic or transcardiac lymphocyte activation in unstable angina.

Leukotriene C4is a potent constrictor of smooth muscle in vitro and may induce coronary vasoconstriction in vivo. To study leukotriene C4release by neutrophils in patients with coronary artery disease, neutrophils were separated from blood samples taken from the coronary sinus and aorta in 20 patients with stable exertional angina and angiographically documented coronary artery narrowings (group I). Eight patients with normal coronary arteries were also studied (group II).To assess leukotriene C4generation, neutrophils were incubated with calcium ionophore A 23187 (0.25 μM) and the supernatants obtained after centrifugation were analyzed for leukotriene C4by radioimmunoassay.Patients in group I had a significantly lower release of leukotriene C4from neutrophils separated from the coronary sinus blood than from those separated from aortic blood (4.33 ± 0.69 versus 5.92 ± 0.54 ng/ml, p < 0.025), whereas patients in group II had a similar rekase of kukotriene C4by the neutrophils separated from coronary sinus blood and from aortic blood (6.0 ± 0.72 versus 6.4 ± 0.66 ng/ml, p = NS). Moreover, in group I patients, a significant correlation was found (p < 0.01) between the extent of coronary artery disease (expressed by the Leaman coronary score) and the percent reduction in leukotriene C4released from neutrophils separated from coronary sinus blood as compared with leukotriene C4produced by neutrophils separated from aortic blood.These data show that neutrophils from patients with coronary artery disease have a reduced ability to produce leukotriene C4after stimulation by calcium ionophore A 23187. The release of leukotriene C4from neutrophils passing through a diseased coronary tree may contribute to the development of the inappropriate vasoconstriction associated with the endothelial dysfunction of atherosclerotic coronary vessels.

OBJECTIVES The aim of the study was to examine the inflammatory cytokines in patients with myocardial ischemia to evaluate whether silent ischemia patients exibit any particular cytokine pattern. BACKGROUND Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Various endogenous mechanisms control a patient’s perceived intensity of pain. Among them, the inflammatory process and the related cytokine production are known to modulate the threshold for activating the primary afferent nociceptors. METHODS Seventy-eight patients with reproducible exercise-induced myocardial ischemia were studied: 34 symptomatic patients, with rest and/or stress angina; 44 asymptomatic patients, with no symptoms during daily life activities or during positive exercise stress test. Venous blood samples were taken from all patients to evaluate the expression of CD11b receptors both on neutrophils and monocytes. Frozen plasma samples (at −80°C) were used to quantify the anti-inflammatory (interleukin-4 and -10, transforming growth factor-β) and the proinflammatory cytokines (tumor necrosis factor-α, interferon-γ, interleukin-1β and -6). RESULTS In asymptomatic patients lower CD11b receptor expression and higher concentration of anti-inflammatory cytokines were observed. Proinflammatory cytokine production was similar in the two groups. CONCLUSIONS The data suggest that an “anti-inflammatory pattern” of cytokine production correlates with silent ischemia and that the immune and inflammatory system activation may be crucial for angina symptoms.

We read with great interest the article by James et al. [(1)][1]in a recent issue of the Journal. We were puzzled by the finding that C-reactive protein (CRP) was related to 30-day mortality, but not to the occurrence of myocardial infarction (MI). Indeed, as shown by Table 3, not only was CRP

Recent research suggests that inflammatory indexes are increased in unstable angina; however it is not known if they reflect inflammatory activity in the coronary arteries or the effects of recurrent ischemia On the myocardium. To address this issue, in 20 pts with unstable angina (defined as recurrent chest pain at rest associated with transient ST-T changes) blood samples were simultaneously taken from the coronary sinus (CS), from aorta (Ao) and from the coronary artery (CA) just distally to the culprit lesion. Surface expression of neutrophils (PMN) and monocytes (MONO) CD11B/CD18 adhesion receptors was detected by direct immunofluorescence evaluated by flow cytofluorimetry using monoclonal antibodies tagged with fluorescent markers. Results are given as molecular equivalents of soluble fluorescein. Ao CA CS PMN 28.5 ± 4.1 23.1 ± 32 37.3 ± 5.1 * † MONO 23.7 ± 3.9 27.6 ± 4.6 33.1 ± 4.8 § * p l 0.02 CS vs Ao † p l 0.0.2 CS vs CA § p l 0.02 CS vs AO These data show that in patients with unstable angina a significant upregulation of CD11B/CD18 adhesion receptors of neutrophils and monocytes occurs in the coronary sinus as compared to the aorta and the culprit lesion site suggesting that leukocyte activation takes place at the microcirculatory level and not within the epicardial coronary arteries.