C-reactive protein, interleukin-6, secretory phospholipase A2 group IIA and intercellular adhesion molecule-1 in the prediction of late outcome events after acute coronary syndromes

OBJECTIVE: We investigated whether levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A(2) group IIA (sPLA(2)-IIA) and intercellular adhesion molecule-1 (ICAM-I) predict late outcomes in patients with acute coronary syndromes (ACS). DESIGN: Prospective longitudinal study. CRP (mg L(-1)), IL-6 (pg mL(-1)), sPLA(2)-IIA (ng mL(-1)) and ICAM-1 (ng mL(-1)) were measured at days 1 (n = 757) and 4 (n = 533) after hospital admission for ACS. Their relations to mortality and rehospitalization for myocardial infarction (MI) and congestive heart failure (CHF) were determined. SETTING: Coronary Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: Patients with ACS alive at day 30; median follow-up 75 months. RESULTS: Survival was related to day 1 levels of all markers. After adjustment for confounders, CRP, IL-6 and ICAM-1, but not sPLA(2)-IIA, independently predicted mortality and rehospitalization for CHF. For CRP, the hazard ratio (HR) was 1.3 for mortality (95% confidence interval (CI): 1.1-1.5, P = 0.003) and 1.4 for CHF (95% CI: 1.1-1.9, P = 0.006). For IL-6, HR was 1.3 for mortality (95% CI: 1.1-1.6, P < 0.001) and 1.4 for CHF (95% CI: 1.1-1.8, P = 0.02). For ICAM-1, HR was 1.2 for mortality (95% CI: 1.0-1.4, P = 0.04) and 1.3 for CHF (95% CI: 1.0-1.7, P = 0.03). No marker predicted MI. Marker levels on day 4 provided no additional predictive value. CONCLUSIONS: In patients with ACS, CRP, IL-6, sPLA(2)-IIA and ICAM-1 are associated with long-term mortality and CHF, but not reinfarction. CRP, IL-6 and ICAM-1 provide prognostic information beyond that obtained by clinical variables.     

Elevated levels of small, low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: possible contribution of phospholipase A2 to this atherogenic profile.

OBJECTIVE: This work studied the presence of inflammatory and atherogenic lipoprotein markers that could explain the high incidence of cardiovascular disease (CVD) reported in rheumatoid arthritis (RA) patients. METHODS: Inflammatory markers were 1) soluble adhesion molecules (intercellular adhesion molecule [ICAM] and vascular cell adhesion molecule [VCAM]), 2) C-reactive protein (CRP), 3) fibrinogen (Fb), 4) cytokines (interferon-gamma [IFNgamma], tumor necrosis factor alpha [TNFalpha]), and 5) secretory group IIA phospholipase A2 (sPLA2-IIA). Atherogenic lipoprotein markers were 1) the size distribution of plasma lipoprotein subclasses, and 2) the binding affinity of low-density lipoprotein (LDL) to chondroitin 6-sulfate glycosaminoglycan (GAG). RESULTS: RA patients (n = 31) and matched controls (n = 28) had similar plasma concentrations of total cholesterol, triglycerides, Apo B, Apo A-I, very low-density lipoprotein, intermediate-density lipoprotein, and high-density lipoprotein (HDL). RA patients had significantly higher plasma levels of sPLA2-IIA, ICAM, CRP, Fb, TNFalpha, and IFNgamma compared with controls. RA patients also had significantly higher levels of small, dense LDL-1 (P < 0.05) and lower levels of small HDL-2 particles (P < 0.001) compared with controls. In addition, LDL from RA patients had a significantly higher binding affinity (Kd) to GAG (mean +/- SD Kd 204+/-22.4 nM Apo B) than did LDL from control subjects (Kd 312+/-36 nM Apo B) (P < 0.05). This Kd value showed a significant negative correlation with the plasma levels of LDL-1 (r = -0.566, P < or = 0.004). In RA patients, a significant positive correlation was obtained between sPLA2-IIA and CRP, ICAM, and LDL-1. HDL-2 showed a negative correlation with sPLA2-IIA. CONCLUSION: These atherogenic lipoprotein factors combined with the presence of chronic inflammation may contribute to the high CVD-related mortality in RA patients.     

Rofecoxib, a COX-2 inhibitor, lowers C-reactive protein and interleukin-6 levels in patients with acute coronary syndromes

BACKGROUND: Patients with acute coronary syndromes (ACS) have high levels of inflammatory mediators such as C-reactive protein (CRP) and interleukin (IL)-6. AIM: To evaluate whether patients with ACS treated with rofecoxib, a COX-2 inhibitor, will have reduced CRP, IL-6, and soluble tumor necrotic factor receptor-1 (sTNF-R1) levels and improved endothelial function. METHODS AND RESULTS: Thirty-four patients hospitalized with ACS were randomized to receive rofecoxib, 25 mg/d plus aspirin 100 mg/d, or placebo plus aspirin, 100 mg/d, for a period of 3 months. Blood samples for CRP, IL-6, and sTNF-R1 levels were drawn prior to randomization, and after 1 month and 3 months. CRP levels in the rofecoxib group (n = 18) were significantly lower both at 1 month and 3 months compared to the baseline levels (p < 0.02). IL-6 levels were significantly lower at 1 month (p < 0.02) in the rofecoxib group, but not at 3 months. There was no change in endothelial function or sTNF-R1 levels. CONCLUSION: Patients recovering from ACS had lower levels of CRP and IL-6 at 1 month and lower CRP levels at 3 months when treated with rofecoxib plus aspirin. Suppression of inflammatory processes may lead to retardation of coronary atherosclerosis and coronary events.     

Peripheral levels of matrix metalloproteinase-9, interleukin-6, and C-reactive protein are elevated in patients with acute coronary syndromes: correlations with serum troponin I

BACKGROUND: Acute coronary syndromes (ACS) are characterized by activation of systemic and local inflammatory mediators. The interrelation between these soluble inflammatory markers and their association with markers of myocardial necrosis have not been extensively studied. HYPOTHESIS: The study was undertaken to evaluate the association of the systemic levels of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), with C-reactive protein (CRP), interleukin-6 (IL-6), and serum troponin-I in patients admitted with ACS. METHODS: Analysis of serum concentrations of the above inflammatory markers was performed in 53 patients with unstable angina (UA) and in 15 with non-ST-segment elevation myocardial infarction (NSTEMI) within 48 h of admission, and 34 patients with stable coronary artery disease. RESULTS: Compared with patients with stable angina, those with ACS had elevated admission levels of MMP-9 (p = 0.04), CRP (p < 0.001), and IL-6 (p = 0.001), but not TIMP-1 (p = 0.55). Compared with patients with UA, those with NSTEMI also had higher levels of IL-6 (p < 0.001), CRP (p = 0.002), and MMP-9 (p = 0.05). CONCLUSIONS: In patients with ACS, the admission levels of inflammatory mediators, including MMP-9, CRP, and IL-6 are significantly elevated, specifically in association with serum troponin I. Systemic and local markers of inflammatory activity may be directly associated with myocardial injury.     

Inflammatory markers and coronary interventions: a potentially useful follow-up modality after stenting.

Periprocedural levels of various inflammatory markers have been correlated with prognosis in patients undergoing percutaneous coronary interventions. However, long-term variations of interleukin-1 receptor antagonist (IL-1Ra) or C-reactive protein (CRP) during follow-up after coronary interventions were not previously investigated. The aim of our study was to perform serial evaluations of these markers before and after coronary stenting and to correlate them with clinical status. Plasma levels of IL-1Ra and CRP were measured at baseline and 3 and 6 months after the procedure in 31 patients with symptomatic coronary artery disease undergoing stent implantation, who had no evidence of myocardial ischemia at 6-month follow-up. While at 3 months there were no significant variations of baseline values, 6 months after the procedure a significant decrease from baseline was observed both in IL-1Ra and CRP levels (median -24 pg/ml, P = 0.048, and -0.13 mg/dl, P = 0.017, respectively). Six-month reduction in both IL-1Ra and CRP levels was significant in patients with unstable angina (n = 18; IL-1Ra: from 175 to 119 pg/ml, P = 0.001; CRP: from 0.52 to 0.18 mg/dl, P = 0.002) and nonsignificant in those with stable angina (n = 13) on admission (IL-1Ra: from 123 to 158 pg/ml, P = 0.22; CRP: from 0.19 to 0.10 mg/dl, P = 0.44). In conclusion, a significant reduction of IL-1Ra and CRP levels is observed 6 months after stent implantation in patients with preprocedural unstable angina who remain free of ischemia. This decrease suggests a stabilization of the inflammatory process and may be associated with a favorable prognosis after coronary interventions.     

Effect of hormone replacement therapy on inflammation-sensitive proteins in post-menopausal women with Type 2 diabetes.

AIMS: To test the effect of oral hormone replacement therapy (HRT) on plasma C-reactive protein (CRP), soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1) and IL-6 concentrations and leucocyte count in post-menopausal women with Type 2 diabetes. METHODS: Post-menopausal women with Type 2 diabetes (n = 61) were randomized in a double-blind fashion to receive either continuous combined hormone replacement therapy (n = 29) with conjugated equine oestrogen (0.625 mg/day) plus medroxyprogesterone acetate (2.5 mg/day) or placebo (n = 32) for 6 months. Study variables were measured at baseline and at the end of the study. RESULTS: Eight women randomized to hormone replacement therapy and four women assigned to placebo group dropped out of the study. Plasma CRP increased (2.2 mg/l, 95% confidence interval 0.3-4.1 mg/l) significantly (P = 0.02) in women treated with HRT (n = 21) compared with placebo (n = 29) taking baseline CRP, body mass index (BMI) and smoking status into account. Plasma levels of cell adhesion molecules, IL-6 and leucocyte count did not change significantly during the study. CONCLUSIONS: These findings indicate that oral HRT with conjugated equine oestrogen plus medroxyprogesterone acetate increases plasma CRP levels but not necessarily global inflammatory activity in post-menopausal diabetic women. An increase in plasma CRP may potentially increase risk of a cardiovascular event.     

Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: a factor analysis approach

BACKGROUND: Numerous inflammatory mediators such as C-reactive protein (CRP), fibrinogen, interleukin-18 (IL-18), and inter-cellular adhesion molecule-1 (ICAM-1) have been proposed for risk stratification in acute coronary syndrome (ACS) patients. However, interactions between these markers have made it difficult to assess their true role in risk prediction. Factor analysis is a multivariable statistical technique that reduces a large number of intercorrelated variables to a smaller set of independent clusters, underlining physiological relationships. The aim of this study was to investigate, using factor analysis, a clustering of pro-inflammatory markers, anti-inflammatory cytokines such as interleukin-10 (IL-10) and HDL cholesterol, and to determine their role in prediction of risk of recurrent coronary events in ACS patients. METHODS: We assessed 320 consecutive patients (236 men; 67 years; IQ 58-74 years) admitted with ACS. The composite of cardiac death and re-hospitalization with non-fatal myocardial infarction, or unstable angina, was the pre-specified study end-point. Serum CRP, fibrinogen, HDL cholesterol, IL-10, IL-18 and ICAM-1 levels were measured at study entry. We assessed independent predictors of the combined end-point during a 1-year follow-up using multiple logistic regression analysis. RESULTS: Factor analysis identified three clusters which were arbitrarily interpreted as (1) a "systemic inflammation" cluster with positive loadings of CRP and fibrinogen, (2) a "local inflammation-endothelial dysfunction" cluster with positive loadings of IL-18 and ICAM-1 and (3) an "anti-inflammation" cluster comprising IL-10 and HDL cholesterol. Only the "anti-inflammation" cluster was a significant predictor (OR 0.66, 95% CI: 0.49-0.89) of adverse cardiac events during a 1-year follow-up and remained significant (OR 0.65, 95% CI: 0.48-0.88) in a multivariate model that included all three factors. CONCLUSIONS: Although inflammatory markers such as CRP predict future cardiovascular events in ACS patients, when all inflammatory mediators are taken into account in a prospective analysis of risk, markers reflecting anti-inflammatory mechanisms are better prognostic markers.     

Psychological stress increases expression of aortic plaque intercellular adhesion molecule-1 and seruminflammatory cytokines in atherosclerotic rabbit model

Plaque rupture,platelet aggregation,and thrombogenesis are the main mechanisms of acute coronary syndrome (ACS),and inflammation factors play key roles in plaque unstability.Psychological stress promotes acute inflammatory response,leading to increased circulating levels of C-reactive protein (CRP),IL-6,and serum intercellular adhesion molecule (sICAM)-1.But it is not clear that whether psychological stress has a direct effect on atherosclerotic plaque stability.The purpose of this study was to investigate effects of chronic psychological stress on inflammatory marker (ICAM-1 ) in atherosclerotic plaque,and inflammatory markers in peripheral blood.Materials and methods Sixty male rabbits were randomized into 2 groups:the control group (n =10) and the atherosclerotic group (n =50).The latter were fed on high fatty diet and were given a large dose of vitamin D3 (3 600 000IU/kg) via intraperitoneal injection.After 8 weeks,the atherosclerotic model was estaslished.Then the 50 atherosclerotic model rabbits were divided into 3 subgroups:no-stress subgroup (n = 16),physiological stress subgroup (n = 16) and psychological stress subgroup (n =18).In physiological stress subgroup and psychological stress subgroup,drinking was cut from twice a day to once a day.At the same time,psychological stress subgroup was given empty bottle stress,and this process lasted for 2 weeks.One hour after the last stress,the blood samples were collected and the serum levels of CRP,IL-6 amd ICAM-1 were tested by radioimmunoassay or enzyme linked immunosorbent assay.The aorta and heart were extracted for pathology examination,and the express of ICAM-1 was tested by immunohistochemical examination.Results (1) After effective atherosclerotic animal model construction,the expression of ICAM-1 in aorta was higher in atherosclerotic group than that in control group (P＜0.01),and was notably higher in psychological stress subgroup than that in no-stress subgroup or in physiological stress subgroup (2.18±0.17 vs 1.58±0.22,1.22±0.15,P＜0.001,respectively).The expression in physiological stress subgroup was higher than that in no-stress subgroup (584±0.22 vs 1.22±0.15,P=0.001).(2) The serum level of IL-6 (51.80±4.60 pg/ml vs 27.60±4.19 pg/ml,8.01±1.39 pg/ml,7.83±1.37 pg/ml),sICAM-1 ( 1.24±0.25 vs 0.85±0.09,0.62±0.17,0.57±0.11),CRP ( 1.004±0.37 vs 0.90±0.29,1.01±0.22,0.71±0.13) in psychological stress group were significantly higher than that in other groups (All P＜0.05).There was a positive relationship between the serum level of CRP,IL-6 and ICAM-1 and the expression of ICAM-1 in aorta wall ( r =0.59,r =0.75,r =0.87,P＜0.01,respectively).Conclusions Psychological stress induces an increased expression of ICAM-1 in aortic atherosclerotic plaque,a higher serum level of CRP,IL-6,and sICAM-1 expression.Psychologial stress has a direct effect on the transition from stability to unstability through in-plaque and out-plaque inflammation.The serum level of CRP,IL-6 and ICAM-1 can reflex the inflammatory degree in atherosclerotic plaque.(J Geriatr Cardiol 2008;5:235-242)     

Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly men with low testosterone levels

OBJECTIVE: Although androgen replacement has been shown to have beneficial effects in hypogonadal men, there is concern that androgens may deleteriously affect cardiovascular risk in elderly men. DESIGN: Anastrozole is an oral aromatase inhibitor that normalizes serum testosterone levels and decreases oestradiol levels modestly in elderly men with mild hypogonadism. Thirty-seven elderly hypogonadal men were randomized to receive either anastrozole 1 mg daily (n = 12), anastrozole 1 mg twice weekly (n = 11), or daily placebo (n = 14) for 12 weeks in a double-blind fashion. PATIENTS: Men aged 62-74 years with mild hypogonadism defined by testosterone levels less than 350 ng/dl. MEASUREMENTS: Serum levels of fasting lipids, C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and homeostatic model assessment (HOMA) scores were measured at 4-week intervals. RESULTS: Treatment with anastrozole did not significantly affect fasting lipids, inflammatory markers (IL-6, CRP), adhesion molecules (ICAM-1, VCAM-1) or insulin sensitivity (HOMA). There was, however, a positive correlation between changes in serum triglycerides and changes in serum oestradiol levels (P = 0.04). CONCLUSIONS: While short-term administration of anastrozole is an effective method of normalizing serum testosterone levels in elderly men with mild hypogonadism, it does not appear to adversely affect lipid profiles, inflammatory markers of cardiovascular risk or insulin resistance.     

Visceral adipose tissue accumulation, secretory phospholipase A2-IIA and atherogenecity of LDL

OBJECTIVE: The aim of the present study was to investigate the combined impact of visceral adipose tissue (VAT) and secretory group IIA phospholipase A(2) (sPLA(2)-IIA) concentrations on the atherogenicity of low-density lipoprotein (LDL) particles among men. SUBJECTS: Analyses were conducted in 74 mid-obese healthy men (age: (mean+/-s.d.) 37.9+/-11.7 years). METHODS: Plasma levels of sPLA(2)-IIA were measured with a commercial ELISA and VAT levels were assessed by computed tomography. Distinct subpopulations of LDL particles were characterized from whole plasma using nondenaturating 2-16% gradient gel electrophoresis.Results:Data indicated that plasma sPLA(2)-IIA levels were approximately 29% (P=0.007) higher among men characterized by a higher accumulation of VAT (>142 vs < or =142 cm(2)). Men having high plasma sPLA(2)-IIA levels (> or =127.2 ng/dl, the median value), were characterized by higher levels of plasma cholesterol (C) and apolipoprotein (apo) B, LDL-C, LDL-apoB, oxidized LDL (OxLDL) and by smaller LDL particles compared to men with sPLA(2)-IIA<127.2 ng/dl. Multiple regression analyses showed that plasma triglycerides and sPLA(2)-IIA levels explained 22.7 and 11.8% of the variance in LDL peak particle size, respectively. Levels of VAT and of sPLA(2)-IIA were the strongest correlates of OxLDL levels explaining, respectively, 15.0 and 5.5% of their variability. CONCLUSION: Both VAT and sPLA(2)-IIA levels modulate the atherogenecity of LDL by accounting for the reduction in their size and their susceptibility to oxidation.     

心理应激与急性冠状动脉综合征

目的 分析心理应激与急性冠状动脉综合征(ACS)的关系,探讨心理应激是否为诱发ACS发生的危险因素.方法 100例经冠状动脉造影检查及临床表现确诊为冠心病的中青年男性患者,分为ACS组(67例)和稳定性心绞痛(SA)组(33例),进行社会心理应激调查,测定其血清白介素(IL)-6、可溶性细胞间黏附分子(sICAM)-1及C-反应蛋白(CRP)的水平,并对其结果进行对照性分析.结果 (1)心理应激组52例,ACS患者和SA患者分别占78.8%(41例)和21.2%(11例,P=0.009);ACS组有心理应激者明显高于SA组[61.2%(41/67)比33.3%(11/33),P=0.009].(2)心理应激组的血清CRP[(14.82±5.07)g/L比(8.78±4.34)g/L]、IL-6[(101.7±22.2)ng/L比(71.1±23.5)ng/L]及sICAM-1[1(1.41±0.47)mg/L比(0.82±0.37)mg/L]明显高于非心理应激组(均P＜0.01);ACS组血清CRP[(18.91±3.12)g/L比(6.20±2.46)g/L]、IL-6[(114.6±15.2)ng/L比(56.4±15.8)ng/L]及sICAM-1[(1.67±0.39)mg/L比(0.63±0.28)mg/L]水平明显高于SA组(P＜0.01).结论 心理应激可使体内炎症因子分泌增加,从而使动脉粥样硬化斑块由稳定变成不稳定,并通过炎症反应参与了ACS发生、发展.     

Dietary alpha-linolenic acid decreases C-reactive protein,serum amyloid A and interleukin-6 in dyslipidaemic patients

BACKGROUND: Inflammation plays an important role in the pathogenesis of coronary artery disease. We examined whether dietary supplementation with alpha-linolenic acid (ALA, 18:3n-3) affects the levels of inflammatory markers in dyslipidaemic patients. METHODS: We recruited 76 male dyslipidaemic patients (mean age=51+/-8 years) following a typical Greek diet. They were randomly assigned either to 15 ml of linseed oil (rich in ALA) per day (n=50) or to 15 ml of safflower oil (rich in linoleic acid (LA, 18:2n-6)) per day (n=26). The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1. Dietary intervention lasted for 3 months. Blood lipids and C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) levels were determined prior and after intervention. CRP and SAA were measured by nephelometry and IL-6 by immunoassay. RESULTS: Dietary supplementation with ALA decreased significantly CRP, SAA and IL-6 levels. The median decrease of CRP was 38% (1.24 vs. 0.93 mg/l, P=0.0008), of SAA 23.1% (3.24 vs. 2.39 mg/l, P=0.0001) and of IL-6 10.5% (2.18 vs. 1.7 pg/ml, P=0.01). The decrease of inflammatory markers was independent of lipid changes. Dietary supplementation with LA did not affect significantly CRP, SAA and IL-6 concentrations but decreased cholesterol levels. CONCLUSIONS: Dietary supplementation with ALA for 3 months decreases significantly CRP, SAA and IL-6 levels in dyslipidaemic patients. This anti-inflammatory effect may provide a possible additional mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in primary and secondary prevention of coronary artery disease.     

血红素氧化酶基因启动子GT序列变化与冠状动脉支架术后再狭窄

目的:观察I型血红素氧化酶(HO-1)基因启动子GT重复长短对冠状动脉支架置入术后再狭窄的影响。方法:187例行冠状动脉支架置入术者,6个月时随访再狭窄情况。PCR和DNA测序仪确定HO-1启动子GT重复次数。高敏法测术前及术后24h、48h血浆白介素-6(IL-6)和C反应蛋白(CRP)值。结果:各基因型间术后IL-6和CRP水平及再狭窄发生率无差异,携较短GT者术前血浆IL-6水平比非短GT序列携带者低约33．3％(P=0．0008)。结论:HO-1基因多态性不影响支架置入术后炎症介质水平及再狭窄,但可能影响动脉粥样硬化形成的炎症过程。     

Dynamics of changes of blood inflammatory-oxidative biomarkers in acute coronary syndrome

Some inflammatory cytokines and parameters of low density lipoproteins (LDL) oxidative modification were studied in blood of 250 acute coronary syndrome (ACS) patients--Siberian inhabitants, men and women with myocardial infarction (MI) or unstable angina on first, tenth and thirtieth days of disease. The inflammatory biomarkers in men and women with MI are: increased concentrations of interleukin (IL)-6, IL-8 and C-reactive protein (CRP), especially on the first day of disease. The most significant inflammatory biomarker of ACS is increased CRP level, especially in women. Oxidative biomarkers in men with ACS are increased basal level of LDL lipid peroxidation (LPO) products and decreased LDL resistance to oxidation. Inflammatory-oxidative biomarkers IL-6, IL-8, CRP and basal level of LDL LPO products are correlated and independently associated with MI.     

Effect of preexisting statin use on expression of C-reactive protein, adhesion molecules, interleukin-6, and antioxidized low-density lipoprotein antibody in patients with unstable angina undergoing coronary stenting

BACKGROUND: Statins are believed to reduce coronary heart disease by mechanisms in addition to their well-known cholesterol lowering effect. HYPOTHESIS: We studied the effect of statins on expression of C-reactive protein (CRP), interleukin-6 (IL-6), adhesion molecules, and antioxidized low-density lipoprotein antibody (anti-oxLDL Ab) in patients with unstable angina (Braunwald class IIb or IIIb) undergoing coronary stenting. METHODS: Consecutive 50 patients with unstable angina were included in the study. We classified the study subjects as patients using statins (Group A, n=20, men 10, mean age 62 years) and patients not using statins (Group B, n=30, men 15, mean age 60 years). RESULTS: Baseline levels of inflammatory markers were similar in the two groups. However, 24 h after coronary stenting, serum levels of CRP (2.00 vs. 4.63 mg/l, p < 0.05), intercellular adhesion molecule-1 (ICAM-1) (217 vs. 261 ng/ml, p < 0.01), and anti-oxLDL Ab (8.97 vs. 12.96 U/ml, p < 0.05) were significantly higher in Group B than in Group A. Furthermore, 72 h after coronary stenting, serum levels of CRP (3.00 vs. 5.50 mg/l, p < 0.01) and ICAM-1 (222 vs. 277 ng/ml, p < 0.05) were significantly higher in Group B than in Group A. CONCLUSIONS: Preexisting statin therapy plays a role in reducing the serum levels of CRP, ICAM-1, and anti-oxLDL Ab after coronary stenting in patients with unstable angina. These data support an anti-inflammatory or plaque-stabilizing effect of statin therapy.     

Association between inflammatory markers and the interleukin-6 -174 G/C polymorphism is abolished in peripheral arterial occlusive disease.

AIM: The interleukin-6 (IL-6) -174 G/C polymorphism has been reported to determine IL-6 levels and contribute to the development of cardiovascular disorders. The aim of our study was to evaluate the effect of the IL-6 -174 G/C polymorphism on hemostatic or inflammatory markers in patients with peripheral arterial occlusive disease (PAOD), a common manifestation of obliterative atherosclerosis. METHODS: Plasma IL-6, fibrinogen, C-reactive protein (CRP), tissue plasminogen activator, plasminogen activator inhibitor-1 (PAI-1), fibrinopeptide A and intercellular adhesion molecule-1 levels were determined in PAOD patients (n=50) and healthy controls (n=30) genotyped for the IL-6 -174 G/C polymorphism. RESULTS: In the control group, IL-6, CRP and fibrinogen levels were significantly associated with the IL-6 -174 G/C polymorphism with a gene-dosage effect being the highest in the CC subjects and the lowest in those with the GG genotype (P<0.0001, P=0.0002 and P=0.0001, respectively). Interestingly, the CC homozygotes had lower PAI-1 levels than carriers of the G allele (P=0.04). In PAOD patients, the IL-6 -174 G/C polymorphism had no effect on all the variables measured. CONCLUSION: In contrast to apparently healthy subjects, the IL-6 -174 G/C polymorphism showed no association with plasma IL-6, CRP, fibrinogen and PAI-1 levels in PAOD patients.     

经皮冠状动脉介入治疗术后炎症指标对急性冠脉综合征患者预后影响

目的 前瞻性观察接受经皮冠状动脉介入治疗（percutaneous coronary intervention,PCI）的急性冠脉综合征患者PCI术后中性粒细胞/淋巴细胞比值（neutrophil to lymphocyte ratio,NLR）、血小板/淋巴细胞比值（platelet to lymphocyte ratio,PLR）、C反应蛋白（ C-reactive protein?,CRP）、降钙素原（procalcitonin,PCT）、白细胞介素-6（interleukin-6,IL-6）等炎症指标水平对近期预后的影响。方法　214例急性冠脉综合征患者行PCI治疗手术后次日清晨,抽取外周肘静脉血行全血细胞测定（计算NLR和PLR）和 CRP、PCT、IL-6等炎症因子检测。应用二分类Logistic 多因素回归模型分析急性冠脉综合征PCI术后主要心脏不良事件 (?major adverse cardiac events,MACE)?发生的影响因素;ROC曲线评估上述炎症指标对急性冠脉综合征患者PCI术后MACE发生的预测价值。结果　214例急性冠脉综合征患者,平均随访12月（中位数）,共累计33例患者（15.4%）出现MACE事件。应用二分类Logistic 多因素回归模型分析,发现NLR[（odds ratio,OR值）2.98,P<0.001]和急性冠脉综合征类型（OR=0.29,P=0.048）是PCI术后MACE发生的独立影响因素。ROC曲线评估分析发现,NLR、PLR、CRP、PCT、IL-6均有预测PCI术后MACE发生的价值（P<0.01）,但是NLR预测MACE发生的ROC曲线下面积最大（0.898）,NLR预测PCI术后MACE事件发生最佳切点为3.94。结论 PCI术后NLR、PLR、CRP、PCT、IL-6等炎症指标均具有预测PCI术后MACE发生的价值,而NLR的预测价值最高。PCI术后过高的NLR和急性ST段抬高型心肌梗死是急性冠脉综合症患者PCI术后MACE发生的独立影响因素。     

急性冠状动脉综合征患者白细胞介素-10及白细胞介素-6表达

目的:通过与C反应蛋白(CRP)检测对比,探讨抗炎因子白细胞介素(IL)-10、促炎因子IL-6与急性冠状动脉综合征(ACS)的关系。方法:冠心病患者78例,其中ACS患者40例(ACS组),稳定型心绞痛(SAP组)患者38例,33例胸痛综合征(CPS组)患者作为对照。所有患者均行冠状动脉造影检查。采用ELISA法检测血浆IL-6、IL-10水平,采用免疫比浊法测定CRP值。结果:与SAP组及CPS组相比,ACS组血浆IL-10水平明显降低,IL-6、CRP水平明显升高,差异有统计学意义;SAP组IL-10水平低于CPS组,IL-6、CRP水平高于CPS组,差异无统计学意义;血浆IL-10水平与IL-6及CRP水平呈负相关,IL-6水平与CRP水平正相关。结论:血浆IL-10水平降低和IL-6、CRP值升高对患者ACS的发生有预测价值。抗炎因子和促炎因子水平的失衡是导致斑块不稳定、急性冠状动脉事件发生的重要因素。     

Growth hormone reduces inflammation in postmenopausal women with abdominal obesity: a 12-month, randomized, placebo-controlled trial

CONTEXT: Abdominal obesity is associated with low GH secretion, elevated circulating markers of inflammation, and increased risk of cardiovascular disease. OBJECTIVE: The objective was to study the effect of GH treatment on inflammatory markers and vascular adhesion molecules in postmenopausal women with abdominal obesity. DESIGN: Forty women aged 51-63 yr received GH (0.67 mg/d) in a randomized, double-blind, placebo-controlled, 12-month trial. Measurements of inflammatory markers [highly sensitive C-reactive protein (CRP), IL-6, and amyloid polypeptideA] and markers of endothelial dysfunction (soluble E-selectin, vascular adhesion molecule-1, intercellular molecule-1, and matrix metalloproteinase-9) were performed at baseline and after 6 and 12 months of treatment. RESULTS: After 12 months, the mean IGF sd score was 0.9 +/- 1.5 and -0.8 +/- 0.6 in the GH and placebo groups, respectively. GH treatment reduced CRP and IL-6 levels compared with placebo (P = 0.03 and P = 0.05, respectively), whereas the markers of endothelial dysfunction were unaffected. Within the GH-treated group, a reduction was shown in CRP (4.3 +/- 4 to 3.0 +/- 3 mg/liter; P < 0.05) and in IL-6 (4.4 +/- 2 to 3.3 +/- 2 ng/liter; P < 0.01). In the GH-treated group, the decrease in CRP and IL-6 correlated with a reduction in visceral adipose tissue (r = 0.7, P < 0.001 and r = 0.5, P < 0.05, respectively). CONCLUSION: GH treatment in postmenopausal women with abdominal obesity reduced serum markers of systemic inflammation. Circulating markers of endothelial dysfunction were unaffected by treatment.     

2型糖尿病患者血清炎性因子与颈动脉粥样硬化的相关性研究

目的 研究2型塘尿病患者血清炎性因子水平与颈动脉粥样硬化的关系.方法 选择124例2型糖尿病患者,采用酶联免疫吸附法测定血清内皮细胞猫附分子1（ICAM-1）、血管细胞黏附分子1（VCAM-1）,E选择素、白细胞介素6（IL-6）和C反应蛋白（CRP）水平;按颈动脉超声检查结果将糖尿病患者分为颈动脉正常组（38例）、颈动脉增厚组（40例）和颈动脉斑块组（46例）.选择40例健康体检者作为对照组,比较各组血清炎性因子水平.结果 ①颈动脉正常组血清ICAM-1,IL-6及CRP较对照组升高,颈动脉增厚组ICAM-1、VCAM-1、IL-6及CRP水平高于颈动脉正常组,颈动脉斑块组ICAM-1、VCAM-1、E选择素高于颈动脉增厚组,上述指标各组差异均有统计学意义,P 〈0.05,或P〈0.01.②相关性分析显示,颈动脉内-中膜厚度（IMT）增厚程度与糖化血红蛋白（HbAlc）（r=0.472）、ICAM-1（r=0.501）、VCAM-1（r = 0.484）、E选择素（r＝0.289）、IL-6（r=0.425）及CRP（r=0.381）呈正相关.患者HbAlc与ICAM-1、VCAM-1、IL-6及CRP呈正相关.ICAM-1、VCAM-1、E选择素、IL-6、CRP间呈正相关,均P〈0.01或P〈0.05.结论 炎性反应参与了2型糖尿病患者颈动脉粥样硬化的发病过程,血清炎性因子水平可以在一定程度上反映糖尿病患者的颈动脉粥样硬化程度.