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• W2115537144 abstract "Inflammation is increasingly thought to play a key role in promoting coronary atherosclerosis 1. Inflammatory markers, such as C-reactive protein (CRP) have been found to be elevated in patients with acute coronary syndromes and to be predictive of adverse cardiac events 2–5. Similarly, increased levels of inflammatory cytokines have been shown in congestive heart failure 6 (CHF) and follow the progression of the disease to its terminal phases 7 (end-stage CHF). Whether activation of the inflammatory-immune system is induced in the early phases of ischaemic left ventricular dysfunction (LVD) remains to be determined. In the present study, we evaluated plasma levels of the prototypical acute phase protein CRP, Interleukin-1 receptor antagonist (IL-1Ra) which is synthesized and released by activated monocyte-macrophages at sites of tissue damage/inflammation and Interleukin-2 soluble receptor (sIL-2R), a specific marker of T-lymphocyte activation, in patients with mild ischaemic LVD. Plasma levels of CRP, IL-1Ra and sIL-2R were determined in 40 consecutive patients referred to the catheterization laboratory for left ventricle and coronary angiography with suspected coronary artery disease (median age 61 years, six females). Nineteen patients (48%) had recent onset of rest angina while the other patients (52%) had a clinical history of stable effort-induced angina. In all cases significant coronary artery disease was demonstrated at angiography. History of previous myocardial infarction was present in 22 cases (55%). At the time of enrollment, none of the patients had clinical or laboratory evidence (nor was there a suspicion) of malignancy, infections, inflammatory diseases, or recent (<2 months) surgery or trauma. In all patients, white blood cell count and erythrocyte sedimentation rate were in the normal range. Venous blood samples to assess CRP, IL-1Ra and sIL-2R levels were collected 3–6 h before heart catheterization. Syringes were anticoagulated with sodium citrate for detection of CRP and ethylenediaminetetraacetic acid (EDTA) for detection of sIL2-R and IL-1Ra. Each extract was frozen at −80 °C, until it was assayed. CRP, sIL-2R and IL-1Ra were determined by enzyme-linked immuno-assay kits purchased from Immunodiagnostik (CRP) or R&D Systems (IL-1Ra and sIL-2R). Values are expressed as median and interquartile range. The Chi-square test was applied to compare discrete variables and the non-parametric U-Mann Whitney test was used to compare continuous non-paired not normally distributed variables. The Spearman rank test was used for correlations between variables. P values <0.05 were considered significant. Left ventricular ejection fraction (LVEF), calculated on quantitative angiography, ranged from 35 to 70%, median 60%. LVEF values between 51 and 70% were considered in the normal range. Mild to moderate LVD (LVEF≤50%) was present in 13 cases (32%). Symptoms consistent with NYHA class II were reported by eight of the 13 patients (61%) while the other five patients were asymptomatic (class I). Cardiovascular risk factors and clinical characteristics of the patients in the two groups are shown in Table 1. Soluble IL-2R plasma levels, but not CRP or IL-1Ra, were found to be significantly elevated in patients with LVD compared to the others [1605 pg/ml (1390–1773pg/ml) vs. 1183 pg/ml (1001–1485 pg/ml); P=0.03] (Fig. 1a). Consistent with previous observations 8, plasma sIL-2R levels were significantly correlated with the age of the patients (R=+0.44; P=0.01). In addition, we found a significant correlation between sIL-2R and LVEF at angiography (R=−0.30; P=0.03) (Fig. 1a) at univariate analysis, but not to other demographic or clinical factors (including presence of previous myocardial infarction). At multivariate analysis, both LVEF and age remained significantly correlated with plasma sIL-2R (P=0.01 and 0.009, respectively). When subgroup analysis was performed, by considering data from 19 patients aged 60 or younger, a significant negative correlation between LVEF and sIL-2R levels was found (R=−0.60; P=0.005). In this subset of patients, the difference in sIL-2R between those with depressed (35–50%) vs. preserved (>50%) LVEF was even more evident [1680 pg/ml (1484–1805 pg/ml) vs. 1125 pg/ml (937–1215 pg/ml), respectively; P=0.004] (Fig. 1b). Soluble IL-2R levels were not correlated with cardiac risk factors, clinical pattern, previous myocardial infarction, number of vessels affected at coronary angiography, CRP, or IL-1Ra plasma levels. Prevalence of LVD among patients with sIL-2R levels above median was significantly greater vs. the others in the entire population [53 vs. 17%, RR 3.68 (1.19–11.42); P=0.024](Fig. 2a) and particularly in the subgroup of patients aged 60 or younger [67 vs. 0%, P=0.002] (Fig. 2b). Activated T-cells release IL-2 and a soluble form of the IL-2 receptor, consisting in the α chain of the αβγ complex that constitutes the functional membrane receptor 8. The sIL-2R has a low affinity for IL-2 and a still poorly defined anti-inflammatory activity. It represents, however, a reliable marker of T-lymphocyte activation 8. Selective elevation of sIL-2R in mild ischaemic LVD suggests activation and, hence, involvement of antigen-specific T-lymphocytes in this condition. In contrast to NYHA class III–IV CHF, mild phases of the disease (class I–II) constitute a fairly asymptomatic condition, well tolerated by the patients although irreversibly associated with myocardial damage and progression of the disease. Inflammatory cytokines (e.g. TNF-α) and Brain-type Natriuretic Peptide (BNP) plasma levels were found to be very useful markers in severe disease or in acute decompensation of chronic CHF, while they offer minimal help in the detection of its earlier stages 6,7,9,10. In turn, elevated CRP levels are considered unfavorable prognostic factors in ischaemic heart disease in regard to acute events. Of note, neither CRP nor IL-1Ra levels, CAD extent on angiography, or prior myocardial infarction correlated with plasma sIL-2R levels or with the presence of LVD in these patients. Hence, T-lymphocyte activation appears to be independent from classic clinical predictors and independent from the acute phase reaction. Further studies are required to confirm our data, which suggest a role of T-lymphocytes in promoting LVD and to evaluate the potential diagnostic value of elevated plasma sIL-2R levels. Consistent with our findings, elevated sIL-2R levels were found in idiopathic dilated cardiomyopathy 11 and associated with a worse prognosis 12." @default.
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• W2115537144 title "Plasma concentrations of interleukin-2 soluble receptor in mild ischaemic left ventricular dysfunction" @default.
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• W2115537144 doi "https://doi.org/10.1016/s1388-9842(02)00117-4" @default.
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