Circulating ICAM-1 and VCAM-1 levels in patients with obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS)-induced hypoxic stress modulates circulating inflammatory mediators causing accelerated atherogenesis. OBJECTIVES: We hypothesized that OSAS-induced hypoxia might result in cardiovascular disease due to increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial surface. METHODS: Thirty-nine subjects with moderate-to-severe OSAS and 34 non-apneic controls matched for age, gender, body mass index (BMI), smoking history, and cardiovascular disease were included in this prospective study. Overnight polysomnography was performed. Circulating ICAM-1 and VCAM-1 levels in the serum were measured by enzyme-linked immunosorbent assay. RESULTS: Circulating levels of both ICAM-1 (480.1 +/- 216.7 vs. 303.4 +/- 98.6 ng/ml, p < 0.0001) and VCAM-1 (1,156.6 +/- 79.8 vs. 878.8 +/- 71.1 ng/ml, p = 0.002) were significantly increased in the OSAS group compared to the control group. For an ICAM-1 cutoff level of 375 ng/ml, predictive sensitivity and specificity for OSAS were 69.2% (95% confidence interval, CI: 52.4-83.0%) and 82.4% (95% CI: 65.5-93.2%), respectively. For a VCAM-1 cutoff level of 859 ng/ml, predictive sensitivity and specificity for OSAS were 74.4% (95% CI: 57.9-86.9%) and 64.7% (95% CI: 46.5-80.2%), respectively. There was a significant positive correlation between circulating levels of ICAM-1 and ln of AHI (r = 0.276, p = 0.018). Multiple logistic regression analyses showed that OSAS was associated with high ICAM-1 and high VCAM-1 levels independent of age, gender, BMI, smoking status and cardiovascular disease. CONCLUSION: We conclude that OSAS can independently increase circulating levels of adhesion molecules     

Usefulness of preoperative C-reactive protein and soluble intercellular adhesion molecule-1 level for predicting future cardiovascular events after coronary artery bypass grafting

High levels of C-reactive protein and soluble intercellular adhesion molecule-1 are associated with increased risk for cardiovascular events. No long-term data are available on predictive value of preoperative levels of C-reactive protein and soluble intercellular adhesion molecule-1 on outcome after coronary artery bypass grafting. We measured baseline levels of C-reactive protein and soluble intercellular adhesion molecule-1 in preoperative serum stored at -80 degrees C in 87 patients with coronary artery disease before undergoing isolated coronary artery bypass grafting. Follow-up was performed after a mean duration of 7.6+/-0.1 years, and all cardiovascular events were recorded. Data were analyzed by categorizing patients into 2 groups according to median value of C-reactive protein and soluble intercellular adhesion molecule-1. During follow-up, 16 patients developed a cardiovascular event. In patients with C-reactive protein above the median (1.9 mg/L), the cumulative cardiovascular event incidence was 29% compared with 9% in patients with levels below the median (p=0.048). In Cox regression analysis that was corrected for age, gender, and conventional risk factors, the adjusted relative risk of cardiovascular events of C-reactive protein above the median was 3.9 (95% confidence interval 1.1 to 13.9, p <0.05). Soluble intercellular adhesion molecule-1 level above the median (136 microg/L) was associated with a cumulative cardiovascular event incidence of 21% versus 16% below the median (p=0.48). In conclusion, in patients who undergo coronary artery bypass grafting, high preoperative levels of C-reactive protein levels, but not of soluble intercellular adhesion molecule-1, were associated with long-term risk of cardiovascular events, independent of other cardiac risk factors.     

Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and incident coronary heart disease: the PRIME Study

The Epidemiological Study of Myocardial Infarction Study which enrolled 9758 apparently healthy men aged 50-59 years, is a prospective cohort study designed to evaluate markers of coronary risk. Soluble forms of the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels were measured in plasma obtained at baseline from 317 subjects who suffered a coronary event during the 5-year follow-up and in twice the number of control subjects who were matched for center, age and day of inclusion in a nested case-control design. The relative risk associated with the highest compared with the lowest thirds of ICAM-1 (>625 versus <502 ng/ml) was 2.45 (95% CI: 1.64-3.65, P<0.001) without adjustment; it decreased moderately (RR: 2.09; 95% CI: 1.34-3.24, P<0.001) after control for lipid and non-lipid factors and remained significantly elevated after adjustment for C-reactive protein (CRP) (RR: 1.90; 95% CI: 1.21-2.96, P=0.005). Plasma ICAM-1 was essentially associated with the risk of myocardial infarction or coronary death and also with angina pectoris. Subjects with CRP presented elevated coronary risk only if ICAM-1 was high. An elevated level of VCAM-1 was not associated with any risk of future acute coronary event, or with angina pectoris. This data indicates that plasma levels of ICAM-1 may serve as risk markers for future coronary events whatever their clinical presentation and that risk is better defined using simultaneous measurements of ICAM-1 and CRP than any of these levels separately.     

apoB/apoA-I ratio is related to femoral artery plaques and is predictive for future cardiovascular events in healthy men

OBJECTIVES: The aim of the present study was to investigate the association between serum concentrations of apoB, apoA-I and the apoB/apoA-I ratio and future cardiovascular events in a group of healthy 58-year-old men during 6.6 years of follow-up. A further aim was to investigate the concentrations of apoB, apoA-I and the apoB/apoA-I ratio to the association of plaque occurrence in the carotid and femoral arteries. BACKGROUND: Previous studies have shown that the apoB/apoA-I ratio is an important cardiovascular risk factor, whereas the association between apoB/apoA-I ratio and presence of atherosclerotic plaques in the carotid and femoral arteries has been less investigated. METHODS: The carotid and femoral arteries were examined by high-resolution B-mode ultrasound in 391, 58-year-old men identified by screening in the city of G?teborg, Sweden. Assessment of plaque occurrence and measurement of apolipoproteins (apoA-I and apoB) was performed. RESULTS: Subjects with an apoB/apoA-I ratio >/=0.9 had a significantly increased risk to suffer a cardiovascular event during 6.6 years of follow-up (OR 3.07, 95% CI 1.22-7.71), while no difference in risk for cardiovascular events was observed for subjects with LDL cholesterol >3.4 mmol/L compared to subjects <3.4 mmol/L (OR 1.04, 95% CI 0.37-2.46). A greater risk for plaques in the femoral artery was also observed in subjects with an apoB/apoA-I ratio >/=0.9 compared to subjects <0.9 (OR 3.06, 95% CI 1.22-7.70). In a multiple logistic regression model, both elevated apoB/apoA-I ratio and plaque occurrence in the femoral artery were of significant importance for cardiovascular events during follow-up. CONCLUSIONS: The results showed that the apoB/apoA-I ratio was associated with arteriosclerosis in the femoral artery, and predicted future cardiovascular events. These observations, and the fact that apoB and apoA-I can be measured in the non-fasting state with high precision, in combination with the finding that LDL cholesterol did not predict cardiovascular disease, support results from other studies that the apoB/apoA-I ratio may be a superior risk marker for cardiovascular disease.     

Circulating cellular adhesion molecules ICAM-1, VCAM-1, P- and E-selectin in the prediction of cardiovascular disease in diabetes mellitus

BACKGROUND: Macrovascular disease in diabetes mellitus is a multifactorial process resulting in part from accelerated atherosclerosis and increased thrombosis. The resultant cardiovascular mortality is up to five times that of an age-matched non-diabetic population. Recently, cell adhesion molecules (CAMs) have been demonstrated in atherosclerotic plaques and implicated in the initiation and development of atherosclerosis. METHODS: To assess circulating CAMs as potential predictors of the development of macrovascular disease in diabetes mellitus, we carried out a 5-year prospective study in 28 diabetic patients without manifest macrovascular disease at entry. Circulating CAMs [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin and E-selectin] were measured at baseline and at follow-up. RESULTS: Except for neuropathy, no patient had other microvascular diabetic complications (retinopathy or nephropathy) or clinically manifest macrovascular disease. Eleven patients developed macrovascular disease at follow-up (seven coronary heart disease, two cerebrovascular disease, two peripheral vascular disease). At baseline, systolic blood pressure and serum creatinine were higher (but within normal range) in patients developing macrovascular disease. Baseline ICAM-1 was significantly higher in the patients who developed macrovascular disease than in those who did not, and it remained so even after adjusting for age, systolic blood pressure, creatinine and glycaemic control (P=0.0007). However, baseline VCAM-1, P-selectin and E-selectin were not found to be associated with macrovascular disease. The risk of developing macrovascular disease was associated with increasing baseline concentrations of ICAM-1 [odds ratios 1.04 (95% CI 1.01-1.07); P=0.01]. No correlation was seen between ICAM-1, HbA(1) and cholesterol. CONCLUSION: This study suggests that ICAM-1 may predict development of macrovascular disease in diabetes mellitus.     

Plasma soluble adhesion molecules; intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin levels in patients with isolated coronary artery ectasia

Plasma soluble adhesion molecules, intercellular adhesion molecule-1 (ICAM)-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin leves of patients with isolated coronary artery ectasia (CAE), patients with obstructive coronary artery disease without CAE and subjects with angiographically normal coronary arteries were evaluated. Patients with isolated CAE were detected to have significantly higher levels of plasma soluble ICAM-1, VCAM-1 and E-selectin in comparison with patients with obstructive coronary artery disease without CAE (ICAM, 673 +/- 153 versus 381 +/- 106, respectively, P < 0.001; VCAM-1, 2366 +/- 925 versus 1136 +/- 208, respectively, P < 0.001; E-selectin, 74 +/- 21 versus 61 +/- 18, respectively, P = 0.01) and subjects with normal coronary arteries (ICAM-1, 673 +/- 153 versus 303 +/- 131, respectively, P < 0.001; VCAM-1, 2366 +/- 925 versus 729 +/- 231, respectively, P < 0.001; E-selectin, 74 +/- 21 versus 49 +/- 9, respectively, P < 0.001), suggesting the presence of a more severe and extensive chronic inflammation in the coronary circulation in patients with isolated CAE. BACKGROUND: The common coexistence of coronary artery ectasia (CAE) with coronary artery disease (CAD) suggests that it may be a variant of CAD. However, it is not clear why some patients with obstructive CAD develop CAE whereas most do not. Inflammation has been reported to be a major contributing factor to both obstructive and aneurysmatic vascular disorders and therefore, in the present study, the plasma soluble adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin levels in isolated CAE were investigated. METHODS: The study population consisted of three groups: the first consisted of 32 patients with isolated CAE without stenotic lesion; the second of 32 patients with obstructive CAD without CAE; and the third group of 30 control subjects with normal coronary arteries. Coronary diameters were measured as the maximum diameter of the ectasic segment by use of a computerized quantitative coronary angiography analysis system. According to the angiographic definition used in the Coronary Artery Surgery Study, a vessel is considered to be ectasic when its diameter is > or =1.5 times that of the adjacent normal segment in segmental ectasia. Plasma soluble ICAM-1, VCAM-1 and E-selectin levels were measured in all patients and control subjects using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Patients with isolated CAE were found to have significantly higher levels of plasma soluble ICAM-1, VCAM-1, and E-selectin in comparison with patients with obstructive CAD without CAE (ICAM, 673 +/- 153 versus 381 +/- 106, respectively; P < 0.001; VCAM-1, 2366 +/- 925 versus 1136 +/- 208, respectively; P < 0.001; E-selectin, 74 +/- 21 versus 61+/-18, respectively; P = 0.01) and control subjects with normal coronary arteries (ICAM-1, 673 +/- 153 versus 303 +/- 131, respectively;, P < 0.001; VCAM-1, 2366 +/- 925 versus 729 +/- 231, respectively; P < 0.001; E-selectin, 74 +/- 21 versus 49 +/- 9, respectively; P < 0.001). In addition, we detected statistically significant positive correlation between the total length of ectasic segments and the levels of plasma soluble ICAM-1 (r = 0.625; P < 0.001), VCAM-1 (r = 0.548; P = 0.001) and E-selectin (r = 0.390; P = 0.027). Multivariate logistic regression analysis revealed a significant independent relation between isolated CAE and ICAM-1 [odds ratio (OR) = 1.023; 95% confidence interval (CI) = 1.0048-1.0414; P = 0.0129] and VCAM-1 (OR = 1.0057; 95% CI = 1.0007-1.0106; P = 0.0240). CONCLUSIONS: We have shown that patients with isolated CAE have raised levels of plasma soluble ICAM-1, VCAM-1 and E-selectin in comparison with patients with obstructive CAD without CAE and control subjects with normal coronary arteries, suggesting the presence of a more severe and extensive chronic inflammation in the coronary circulation in these patients.     

Increased levels of cytokines in the aqueous humor correlate with the severity of diabetic retinopathy

AimsTo determine the associations between the levels of certain cytokines in the aqueous humor and the severity of diabetic retinopathy.MethodsA total of 103 patients (one eye per patient) who received intravitreal injection with ranibizumab for diabetic retinopathy were enrolled and divided into 3 groups: nonproliferative diabetic retinopathy (NPDR) with macular edema group (42 eyes), proliferative diabetic retinopathy (PDR) group (40 eyes) and neovascular glaucoma due to PDR (NVG-PDR) group (21 eyes). The concentrations of interleukin (IL)-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in the aqueous humor were measured.ResultsIn this study, 42, 40 and 21 patients (one eye per patient) were included in the NPDR, PDR and NVG-PDR groups, respectively. The median concentrations of IL-6, IL-8, IL-10, VEGF, TGF-β, VCAM-1, ICAM-1 and MCP-1 in the groups were measured. The levels of these 8 cytokines increased with the severity of diabetic retinopathy, especially in the NVG-PDR group. Compared with those in the NPDR group, the aqueous concentrations of these 8 cytokines were higher in the PDR group and were the highest in the NVG-PDR group. There were significant differences in all cytokines among the three groups (P < 0.05). Multivariate analysis showed that in the NPDR and PDR groups, the risk of PDR associated with elevated levels of TGF-β (P = 0.0004, OR 1.11, 95% CI [1.05–1.18]) and ICAM-1 (P = 0.0408, OR 10.75, 95% CI [1.10–104.61]). In the PDR and NVG groups, the risk of NVG associated with elevated levels of IL-10 (P = 0.0486, OR 0.7040, 95% CI [0.4966, 0.9979]), VEGF (P = 0.0279, OR 0.9963, 95% CI [0.9931, 0.9996]), and VCAM-1 (P = 0.0316, OR 0.9998, 95% CI [0.9996, 0.99998]). In the three groups, the risk of developing NVG associated with elevated levels of TGF-β (P < 0.001, OR 1.04, 95% CI [1.02, 1.05]).ConclusionsThe levels of these eight cytokines in the aqueous humor increased with the severity of diabetic retinopathy, especially in NVG-PDR. This study suggests that TGF-β, ICAM-1, IL-10, VEGF, and VCAM-1 may play a role in the progression of diabetic retinopathy, especially TGF-β, which may plays a significant role in NVG-PDR. These cytokines potentially may be used as biomarkers to predict the progress of diabetic retinopathy, contribute to the choice of treatment options and/or monitor treatment responses.     

Circulating intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in patients with type 2 diabetes mellitus

Serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in patients with type 2 diabetes mellitus (n = 64) and control subjects (n = 40) were studied. Serum ICAM-1 concentrations in diabetic patients were significantly higher than those of control subjects (378.2 +/- 70.0 versus 220.4 +/- 31.8 ng/ml, P < 0.01). By multiple regression analysis, hemoglobin A1c was independently associated with serum ICAM-1 concentration in patients with diabetes. The serum VCAM-1 concentration of diabetic patients with macroangiopathy was higher than those of patients without macroangiopathy and of control subjects (806.9 + 276.5 versus 639.0 +/- 146.0 (P < 0.01), and 652.1 +/- 146.9 ng/ml (P < 0.01), respectively). There was no difference in serum E-selectin concentration between diabetic patients with or without macroangiopathy and normal control subjects. These results suggest that adhesion molecules may contribute to the development of atherosclerosis in the diabetic state.     

Percutaneous transluminal mitral valvuloplasty reduces circulating vascular cell adhesion molecule-1 in rheumatic mitral stenosis

BACKGROUND: The circulating levels of adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), have been demonstrated to be elevated in patients with rheumatic mitral stenosis (MS). However, the impact of percutaneous transluminal mitral valvuloplasty (PTMV) on the elevated circulating levels of VCAM-1 and ICAM-1 in patients with MS has never been investigated. METHODS: and results: A total of 19 patients with symptomatic MS undergoing PTMV were studied (group 1) [15 patients in chronic atrial fibrillation, and 4 patients in sinus rhythm]. The plasma levels of soluble VCAM-1 and ICAM-1 in the femoral vein and artery, and right and left atria before PTMV, and those in the peripheral venous blood at the 1-week and 4-week follow-ups after PTMV were determined by solid-phase sandwich enzyme-linked immunosorbent assay. The mitral valve area was calculated by means of the Doppler pressure half-time method. In addition, we measured plasma concentrations of soluble VCAM-1 and ICAM-1 in the peripheral venous blood samples obtained from 22 control patients (including 14 healthy volunteers in sinus rhythm [group 2] and 8 patients in chronic lone atrial fibrillation [group 3]). The plasma level of soluble VCAM-1 was significantly elevated in group 1 patients (1,205.4 +/- 462.4 ng/mL [mean +/- SD]) compared with group 2 (580.9 +/- 208.0 ng/mL) and group 3 patients (716.4 +/- 221.6 ng/mL) [p < 0.0001]. In group 1 patients, the plasma levels of soluble VCAM-1 and ICAM-1 in the left atrium did not differ from those in the right atrium, femoral vein, or femoral artery (p = 0.668 for VCAM-1, and p = 0.232 for ICAM-1). The area of mitral valve increased significantly after PTMV (1.08 +/- 0.14 cm(2) vs 1.48 +/- 0.33 cm(2), p < 0.0001). The mean left atrial pressure fell significantly after PTMV (22.9 +/- 5.2 mm Hg vs 17.7 +/- 6.0 mm Hg, p < 0.0001). The peripheral venous plasma level of soluble VCAM-1 obtained before PTMV fell significantly after PTMV (before, 1,205.4 +/- 462.4 ng/mL; 1 week after PTMV, 915.7 +/- 280.2 ng/mL; 4 weeks after PTMV, 859.0 +/- 298.7 ng/mL; p < 0.0001). CONCLUSIONS: In patients with moderate-to-severe MS, the venous plasma level of soluble VCAM-1 fell significantly after PTMV, and the elevated plasma soluble VCAM-1 concentration was associated with hemodynamic abnormality rather than with rheumatic activity.     

Supervised exercise training reduces plasma levels of the endothelial inflammatory markers E-selectin and ICAM-I in patients with peripheral arterial disease

Elevated plasma levels of vascular inflammatory markers have been reported in patients with peripheral arterial disease (PAD). We assessed the effect of supervised exercise training (ET) on vascular inflammation, hypothesizing that ET reduces plasma levels of the endothelial adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-I (VCAM-I). Twenty-nine patients with PAD underwent a supervised ET program for 8 weeks. Before and after ET, walking distances (pain-free, PWD; maximal, MWD) were determined by a standard treadmill test. Plasma levels of E-selectin and ICAM-I were significantly reduced (E-selectin: 45.5-40.4 ng/mL, P = .013); ICAM-I: 342.0-298.0 ng/mL, P = .016). VCAM-1 levels were unchanged. Walking distances increased significantly (PWD: median 77-150 m, P < .001; MWD: median 306-535 m, P < .001). In conclusion, 8 weeks of ET in patients with PAD reduces plasma levels of the specific endothelium-derived inflammatory markers E-selectin and ICAM-I.     

Soluble VCAM-1 and E-selectin, but not ICAM-1 discriminate endothelial injury in patients with documented coronary artery disease

It has been shown that endothelial cell adhesion molecules play an important role in the development of coronary atherosclerosis and inflammatory disease. We sought to test whether soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin are increased in patients with documented coronary artery disease (CAD). Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured in 40 patients with documented CAD, 20 subjects with angiographically documented normal coronary arteries, and 14 healthy volunteers. Patients with documented CAD exhibited significant elevation of VCAM-1 (535 +/- 227.1 ng/ml, p = 0.0001), E-selectin (69.4 +/- 29.4 ng/ml, p = 0.006), but not ICAM-1 (320.5 +/- 65.1 ng/ml, p = 0.9) concentrations as compared to subjects with normal coronary arteries (252.3 +/- 79.8, 49.7 +/- 22.0 and 311.4 +/- 40.2 ng/ml), and healthy controls (110.0 +/- 17.7, 29.0 +/- 2.0 and 237.5 +/- 46.5 ng/ml), respectively. Soluble markers of endothelial injury are not uniformly increased in patients with documented CAD as compared to those with normal coronary arteries and healthy controls. However, VCAM-1 and E-selectin, but not ICAM-1 could identify endothelial injury in such patients.     

Soluble intercellular adhesion molecule-1 is related to endothelial vasodilatory function in healthy individuals

OBJECTIVE: To investigate the associations between markers of systemic and vascular inflammation, and indicators of vascular morphology and function. METHODS: In 59 apparently healthy individuals, we measured serum levels of highly sensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatation was evaluated in the forearm by venous occlusion plethysmography and local infusions of methacholine and sodium nitroprussid. Endothelial function index (EFI) was expressed as the EDV/EIDV ratio. The intima-media thickness (IMT) of the common carotid artery was investigated with ultrasound (far wall). RESULTS: EFI was inversely related only to ICAM-1 (r=-0.31, P<0.02) by univariate analysis. This association remained significant after adjustment for age, sex, blood pressure, smoking and serum cholesterol. EFI did not relate to hsCRP, VCAM-1 or E-selectin. Neither hsCRP, nor the adhesion molecules were significantly related to carotid artery IMT. CONCLUSION: ICAM-1 was related to endothelial vasodilatory function, but not to IMT, suggesting that endothelial inflammatory activation is related to an impaired vascular relaxation in apparently healthy individuals.     

Soluble cell adhesion molecules in hypertensive concentric left ventricular hypertrophy

OBJECTIVE : Concentric left ventricular (LV) hypertrophy is an important cardiovascular risk factor. We investigated whether concentric LV hypertrophy is associated with activation of the vascular endothelium, as assessed by measurements of soluble cell adhesion molecules. DESIGN : E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1) were measured in serum from hypertensive patients with LV hypertrophy (64 with concentric and 47 with eccentric hypertrophy) and from two matched control groups consisting of 38 hypertensive patients without LV hypertrophy and 38 normotensive subjects. Carotid artery intima-media thickness (IMT) was examined by ultrasonography and LV mass by echocardiography. Neurohormone activities of the renin-angiotensin-aldosterone system were also measured. RESULTS : E-selectin levels were higher in hypertensive than in normotensive subjects (56 +/- 19 versus 49 +/- 11 ng/ml, P = 0.031). Patients with concentric LV hypertrophy had higher levels of E-selectin (61 +/- 21 versus 49 +/- 15 ng/ml, P < 0.001), ICAM-1 (273 +/- 49 versus 254 +/- 49 ng/ml, P = 0.043), VCAM-1 (591 +/- 131 versus 544 +/- 78 ng/ml, P = 0.038) and greater carotid artery IMT (0.99 +/- 0.26 versus 0.83 +/- 0.15 mm, P = 0.018) than eccentric LV hypertrophy patients. E-selectin and VCAM-1 correlated positively to LV relative wall thickness (P = 0.040 and 0.037, respectively), with a similar trend for ICAM-1 (P = 0.083). E-selectin correlated with serum aldosterone (P < 0.001), and E-selectin and ICAM-1 with plasma angiotensin converting enzyme activity (P = 0.003 and 0.036, respectively). CONCLUSION : Increased levels of soluble cell adhesion molecules and an increased carotid artery IMT characterize concentric LV hypertrophy. This indicates perturbations at the vascular level, involving activation of the vascular endothelium in hypertensive patients with concentric LV hypertrophy.     

Comparison of serum concentrations of soluble adhesion molecules in diabetic microangiopathy and macroangiopathy.

AIMS: To clarify the correlation between serum concentrations of soluble adhesion molecules and diabetic microangiopathy or macroangiopathy in patients with Type 2 diabetes. METHODS: Patients with diabetic retinopathy and intima-media thickness of common carotid artery (CCA-IMT) < 1.1 mm were classified as the microangiopathy group (n = 62). Patients with CCA-IMT > or = 1.1 mm and without retinopathy were classified as the macroangiopathy group (n = 95). Patients with CCA-IMT < 0.9 mm and without retinopathy were assigned to the no complications group (n = 139). Clinical characteristics and soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin levels were compared between the groups. RESULTS: Patients with microangiopathy had a significantly longer duration of diabetes, were hypertensive and more likely to have a positive family history of diabetes than the control group. Patients with macroangiopathy were more likely to be smokers, hypertensive, and have a family history of hypertension. Soluble ICAM-1, VCAM-1, and E-selectin levels were significantly higher in the microangiopathy group than in the control group. Soluble VCAM-1 and E-selectin levels, but not ICAM-1 levels, were significantly elevated in the macroangiopathy group. These results were unchanged after adjustment for age, sex, duration of diabetes, blood pressure, HbA1c, HDL-cholesterol, and smoking status. CONCLUSIONS: Our results suggest that soluble adhesion molecules are related to both diabetic micro- and macroangiopathy. The relative contributions of adhesion molecules may be greater in the former than latter patients with Type 2 diabetes.     

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.     

Clinical significance of serum levels of E-selectin,intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients

OBJECTIVES: This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery. METHODS: The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects. RESULTS: Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage. CONCLUSIONS: These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful.     

Expression of adhesion molecules in peripheral pulmonary vessels from smokers and nonsmokers

Introduction and rationale. An accumulation of intraalveolar cells, especially of macrophages and granulocytes, can be observed in smokers. Since adhesion molecules are involved in the process of cell accumulation, in this study we investigated the hypothesis that the expression of endothelial adhesion molecules on pulmonary vascular endothelial cells is different in smokers and nonsmokers. Methods. We investigated lung biopsies from 26 patients who underwent thoracic surgery for localized malignancies (smokers: 15; nonsmokers: 11). Cryostat sections were stained by using immunohistochemistry (APAAP method) with antibodies against E- and P-selectin, the vascular adhesion molecule-1 (VCAM-1), and the intercellular adhesion molecule-1 (ICAM-1). The number of adhesion molecule-positive stained vessels was compared to the total number of vessels identified by the expression of von Willebrand's factor (vWF) and anti-CD31. Results. The two groups investigated showed no differences in the expression of E-, and P-selectin and of VCAM-1. In contrast, the expression of ICAM-1 was significantly increased in smokers (median 25 vessels/section, CI95%: 19–31) compared to nonsmokers (median 16 vessels/section, CI95%: 9–21) (p = 0.030). In smoking subjects, we were also able to demonstrate a positive correlation between the duration of smoking expressed as pack years and the expression of ICAM-1 on pulmonary vessels (Spearman rank coefficient of correlation 0.857; p = 0.0002). Conclusion. The observed increased expression of ICAM-1 on pulmonary vascular endothelial cells in smokers compared to nonsmokers may be involved in the increased recruitment of inflammatory cells to the alveolar space of smokers.     

Soluble intercellular adhesion molecule-1 and long-term risk of acute coronary events in patients with chronic coronary heart disease. Data from the Bezafibrate Infarction Prevention (BIP) Study

OBJECTIVES: The goal of this study was to assess soluble intercellular adhesion molecule-1 (sICAM-1) level as a predictor of future acute coronary events in patients with chronic coronary heart disease (CHD). BACKGROUND: Increased sICAM-1 concentration has been shown to be associated with the incidence of CHD in healthy persons. Its significance in patients with CHD has been scarcely investigated. METHODS: We designed a prospective, nested case-control study. Sera were collected from patients with CHD enrolled in a secondary prevention trial that evaluated the efficacy of bezafibrate in reducing coronary events. We measured baseline sICAM-1 concentration in the sera of patients who developed subsequent cardiovascular events (cases: n = 136) during follow-up (mean: 6.2 years) and in age- and gender-matched controls (without events: n = 136). RESULTS: Baseline serum concentrations of sICAM-1 were significantly higher in cases versus controls (375 vs. 350 ng/ml; p < 0.05). Each 100 ng/ml increase in sICAM-1 concentration was associated with 1.27 (95% confidence interval [CI]: 1.00 to 1.63) higher relative odds of coronary events. Soluble ICAM-1 concentration in the highest quartile (>394 ng/ml) was associated with significantly higher odds of coronary events (compared with the lowest quartile), even after multivariate adjustment (2.31, 95% CI: 1.02 to 5.50). After adding fibrinogen and total white blood cell count to the multivariate model, the relative odds were 2.12 (95% CI: 0.88 to 5.35) and 2.70 (95% CI: 1.10 to 7.05), respectively. CONCLUSIONS: Elevated sICAM-1 concentration in CHD patients is associated with increased risk of future coronary events independent of other traditional risk factors.     

急性冠状动脉综合征患者冠状动脉循环粘附分子的变化

目的探讨急性冠状动脉综合征患者冠状动脉循环血浆细胞间粘附分子1和血管细胞粘附分子1水平变化的临床意义.方法应用酶联免疫吸附法检测65例冠心病患者(30例急性冠状动脉综合征,35例稳定型心绞痛)及27例对照者冠状动脉循环(冠状静脉窦-主动脉根部)血浆细胞间粘附分子1和血管细胞粘附分子1水平,比较其水平变化与不同冠心病类型之间的关系.结果急性冠状动脉综合征组冠状静脉窦和主动脉根部血浆细胞间粘附分子l和血管细胞粘附分子1水平明显高于稳定型心绞痛组和对照组(P＜0.05);急性冠状动脉综合征组冠状动脉循环(冠状静脉窦与主动脉根部的差值)血浆细胞间粘附分子1和血管细胞粘附分子1水平明显高于稳定型心绞痛组和对照组(P＜0.01).稳定型心绞痛组和对照组冠状静脉窦、主动脉根部和冠状动脉循环血浆细胞间粘附分子1和血管细胞粘附分子1水平无明显差别(P＞0.05).血浆细胞间粘附分子1和血管细胞粘附分子1水平与冠状动脉病变受累支数无关.结论急性冠状动脉综合征时血浆细胞间粘附分子1和血管细胞粘附分子1浓度显著升高,冠状动脉循环血浆细胞间粘附分子1和血管细胞粘附分子1变化反映冠状动脉炎症活动程度,细胞粘附分子参与斑块的不稳定.     

Increased plasma soluble adhesion molecules; ICAM-1, VCAM-1, and E-selectin levels in patients with slow coronary flow

BACKGROUND: Inflammation has been reported to be a major contributing factor to many cardiovascular events. In the present study, we aimed to evaluate plasma soluble adhesion molecules; intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin as possible indicators of endothelial activation or inflammation in patients with slow coronary flow. METHOD: Study population included 17 patients with angiographically proven normal coronary arteries and slow coronary flow in all three coronary vessels (group I, 11 male, 6 female, mean age=48+/-9 years), and 20 subjects with angiographically proven normal coronary arteries without associated slow coronary flow (group II, 11 male, 9 female, mean age=50+/-8 years). Coronary flow rates of all patients and control subjects were documented by Thrombolysis In Myocardial Infarction frame count (TIMI frame count). All patients in group I had TIMI frame counts greater than two standard deviation above those of control subjects (group II) and, therefore, were accepted as exhibiting slow coronary flow. Serum levels of ICAM-1, VCAM-1, and E-selectin were measured in all patients and control subjects using commercially available ELISA kits. RESULTS: Serum ICAM-1, VCAM-1, and E-selectin levels of patients with slow coronary flow were found to be significantly higher than those of control subjects with normal coronary flow (ICAM-1: 545+/-198 ng/ml vs. 242+/-113 ng/ml respectively, p<0.001, VCAM-1: 2040+/-634 ng/ml vs. 918+/-336 ng/ml respectively, p<0.001, E-selectin: 67+/-9 ng/ml vs. 52+/-8 ng/ml respectively, p<0.001). Average TIMI frame count was detected to be significantly correlated with plasma soluble ICAM-1 (r=0.550, p<0.001), VCAM-1 (r=0.569, p<0.001) and E-selectin (r=0.443, p=0.006). CONCLUSION: Increased levels of soluble adhesion molecules in patients with slow coronary flow may be an indicator of endothelial activation and inflammation and are likely to be in the causal pathway leading to slow coronary flow.