Can Internet surveys help us understanding allergic disorders? - results from a large survey in urticaria in Greece.

BACKGROUND: Urticaria is often underdiagnosed and/or undertreated. We have conducted an Internet-based study to record epidemiological and clinical features as well as therapeutic interventions for urticaria in a large sample of patients in Greece. METHODS: A standard anonymous questionnaire was posted for a 3-month period on 'http://www.in.gr', a Greek popular Internet portal. Each individual participated only once. Participants were screened for the presence or history of urticaria by two key questions and were then asked to provide information on symptomatology and management. RESULTS: A total of 12 396 subjects voluntarily responded to the survey, of which 8440 (5136 females) who reported to have or had urticaria, were finally analysed. A total of 4780 (56.6%) had experienced weals only, 507 (6.0%) angio-oedema only and 3018 (35.8%) both. Weals and angio-oedema were found to be more common in women; 2761(57.8%) and 277(54.6%), respectively. Age of onset significantly correlated with disease duration; a 1% higher possibility of longer duration of urticaria exists (more than 6 weeks compared with less than 6 weeks) for each additional year of age of onset after controlling for gender. Patients with chronic urticaria had increased mean age compared with those reporting the acute form (35.04 vs. 33.88 years, P < 0.001). Dermatologists were the most frequently visited specialists and the most common treatments were antihistamines and topical preparations. The self-reported eliciting factors of urticaria were as follows: physical stimuli (approximately 25%), psychological distress (17.2%), direct contact to metals or chemicals (14.5%), foods and drugs (10%), whereas a third of the participants could not identify any trigger. CONCLUSIONS: Internet surveys can be a useful tool for screening the general population for common allergic disorders, such as urticaria.

The diverse associations of uric acid with low-grade inflammation, adiponectin and arterial stiffness in never-treated hypertensives.

The data regarding the role of serum uric acid (SUA) along with subclinical inflammation in the context of hypertensive vascular damage are rather scarce and controversial. Towards this end, we assess the links between SUA, high-sensitivity CRP (hs-CRP), adiponectin and carotid to femoral pulse wave velocity (c-f PWV) in 292 subjects with never-treated stage I-II essential hypertension. On the basis of the median SUA levels (0.31 mmol l(-1)), the study population was divided into subjects with low (n=149) and high (n=143) SUA values. By multiple regression analysis, it was revealed that SUA was independently associated with log hs-CRP (R(2)=0.098; P=0.02), log adiponectin (R(2)=0.102; P=0.03), waist circumference (R(2)=0.049; P=0.04), 24-h systolic blood pressure (SBP) (R(2)=0.179; P=0.001) and estimated glomerular filtration rate (R(2)=0.156; ß (s.e.)=-0.169 (0.023); P=0.02). In addition, c-f PWV was independently associated with age (R(2)=0.116; P<0.0001), waist circumference (R(2)=0.088; P<0.0001), 24-h SBP (R(2)=0.167; P=0.001), log adiponectin (R(2)=0.07; P=0.006) and log hs-CRP (R(2)=0.06; P=0.034). In conclusion, SUA levels are independently associated with hs-CRP and adiponectin levels but not with c-f PWV in essential hypertensive patients. Increased SUA levels are accompanied by a state of pronounced inflammatory activation and hypoadiponectinemia that significantly impairs the arterial stiffness accelerating the vascular ageing process in this setting.

Adherence to the Mediterranean diet and albuminuria levels in Greek adolescents: data from the Leontio Lyceum ALbuminuria (3L study).

BACKGROUND/OBJECTIVES: Mediterranean diet has favorable effects on the cardiovascular system, whereas albuminuria is associated with atherosclerosis progression. The aim of the study was to assess the relationships of adherence rates to the Mediterranean diet with albumin to creatinine ratio (ACR), in a cohort of Greek adolescents who participated in the Leontio Lyceum ALbuminuria (3L) study. SUBJECTS/METHODS: In a total of 365 adolescents 12-17 years of age included in 3L study, ACR values were determined in a morning-spot urine. RESULTS: The Mediterranean diet Quality Index for children and adolescents (KIDMED) was estimated and accordingly subjects were divided into those with high (≥ 8), average (4-7) and low (≤ 3) score. Adolescents with low (n=153, 42%) compared with those with average (n=187, 51.2%) and high (n=25, 6.8%) KIDMED score were characterized by greater ACR values (22.4 vs 13.4 vs 12.1 mg/g, P<0.05) even after adjustment for confounders. In the total population, KIDMED score was related to body mass index (r=0.122, P=0.02), waist circumference (r=0.118, P=0.02), systolic blood pressure (BP) (r=0.119, P=0.023), whereas it was negatively associated with ACR (r=-0.111, P=0.041). Regarding ACR, it was associated with age (r=-0.11, P=0.044), male sex (r=0.16, P=0.003), body mass index (r=-0.131, P=0.016) and systolic BP (r=-0.144, P=0.008). CONCLUSIONS: Adolescents who adhere to the Mediterranean diet exhibit lower levels of albuminuria, independently of demographic and hemodynamic confounders. The inverse relation of KIDMED index with ACR suggests a close link of accelerated vascular damage reflected by albuminuria with low adherence to this favorable diet of the Mediterranean basin.

The role of the cytochrome P450 polymorphisms in clopidogrel efficacy and clinical utility.

Clopidogrel, an antiplatelet agent, prevents platelet aggregation by inhibiting the adenosine disphosphate (ADP) P2Y12 receptor, which is located on the platelet surface. Although dual antiplatelet therapy appears to be efficient, a considerable number of patients continue to experience adverse cardiovascular events, such as stent thrombosis. The percentage of low response to antiplatelet therapy varies from 4% to 30% of patients depending on the cut-off values. In addition, several factors such as poor absorption, drug-to-drug interactions, inadequate dosing, elevated body mass index, insulin resistance and the nature of acute coronary syndromes have been implicated in low clopidogrel response. Recently, studies have focused on the role of genetic polymorphisms encoding enzymes that participate in clopidogrel hepatic metabolism or receptors involved in intestinal absorption and ADP induced platelet aggregation, which may affect the percentage of platelet inhibition after clopidogrel administration. The management of clopidogrel resistance remains a controversial issue and additional studies are required to evaluate the safety and efficacy of increased loading of clopidogrel or replacement with other new antiplatelet agents such as prasugrel.

Inflammatory biomarkers predicting events in atherosclerosis.

Recent evidence suggests that vascular inflammation plays important role in the pathogenesis and the clinical evolution of atherosclerosis. Several circulating inflammatory biomarkers such as acute phase proteins, adhesion molecules and pro-inflammatory cytokines along with biomarkers, proposed the last few years, have clarified the role of inflammation in atherosclerosis. In particular a number of studies have focused on the positive predictive role of C-reactive protein in populations without prior cardiovascular disease. As regards to fibrinogen studies have shown a positive role in predicting cardiovascular events. However, the potential prognostic role of adhesion molecules and cytokines for cardiovascular events is unclear. Thus, further studies are required to evaluate the predictive role of such molecules, as well as others under investigation in states of atherosclerosis.

Prognostic clinical and angiographic characteristics for the development of a new significant lesion in remote segments after successful percutaneous coronary intervention.

BACKGROUND: The majority of cardiovascular events in patients undergoing PCI arise from the progression of NCL during the long-term follow-up period. The purpose of the study was to investigate the clinical and angiographic factors related to the progression of non-culprit lesions (NCL) of patients undergoing percutaneous coronary interventions (PCI). METHODS: One hundred and seventeen patients that underwent two coronary angiograms with a time interval greater than 3 months were enrolled. All patients underwent PCI as a treatment for the culprit lesion. In the second coronary angiography we investigated whether they had a new culprit lesion clearly differentiated from the one of the first angiogram. The demographic characteristics, the clinical syndrome responsible for the first PCI and the procedural characteristics were recorded. Quantitative coronary angiography was performed at the culprit lesion of the second angiography and in the same lesion in the first angiography. RESULTS: Multivariate analysis showed that the independent variables for the development of a significant lesion at the follow-up requiring intervention were: the presence of complex lesion (53.78% vs 36.22%, p<0.001, OR=39.42), acute myocardial infarction (AMI) at the initial diagnosis (36.3% vs 32.4%, p<0.001, OR=3.9), and smoking (46.15% vs 53.84%, p=0.03, OR=0.29). CONCLUSIONS: Patients with AMI and complex morphology of NCL have increased risk for a new intervention after successful PCI. Smoking at the time of the follow up, was associated with fewer coronary interventions.

Circulating biomarkers for the diagnosis and prognosis of heart failure.

Despite substantial therapeutic advances, heart failure remains a syndrome associated with high morbidity and mortality. The management of heart failure remains challenging despite the recent different therapeutic advances. The emergence of cardiac biomarkers as increasingly effective clinical tools suggests the potential of a new approach to the management of patients with heart failure. A variety of circulating biomarkers of diagnostic and prognostic utility in heart failure is currently being studies in preclinical, observational and randomized prospective studies. Of the various candidate biomarkers, the greatest wealth of knowledge and clinical experience lies with the B-type naturetic peptides. However, because individual biomarkers may have limited sensitivity and specificity, a multi-marker approach, using combinations of different biomarkers that reflect different aspects of the pathophysiological milieu, would contribute to better risk stratification and optimization of therapy.

Impact of type 2 diabetes mellitus on diffuse inflammatory activation of de novo atheromatous lesions: implications for systemic inflammation.

AIMS: Local coronary and systemic inflammation is pronounced in patients with diabetes mellitus (DM). Intracoronary thermography detects local inflammation and C-reactive protein (CRP) is a marker of systemic inflammation. We investigated whether or not, in patients with DM, thermal heterogeneity of culprit lesions (CLs) correlates with that of non-culprit lesions (NCLs) and with systemic inflammation. METHODS: We included DM patients who had two angiographically significant lesions and were undergoing percutaneous coronary intervention. We measured the temperature difference (DeltaT) between the lesion and proximal vessel wall. RESULTS: We included 104 (n=208 lesions) patients: 32 (n=64 lesions) had DM and 72 (n=144 lesions) were non-DM (control group). DeltaT was increased in DM in both CLs and NCLs (CLs: DM=0.12+/-0.06 degrees C; no DM=0.06+/-0.04 degrees C; P<0.01 versus NCLs: DM=0.13+/-0.08 degrees C versus no DM=0.06+/-0.05 degrees C; P<0.01). Patients with DM had similar DeltaT in CLs and NCLs (P=0.49). A linear correlation was detected between heat production in all lesions and CRP (R=0.45; P<0.01), which was attributed to the correlation of DeltaT in lesions of patients with DM and CRP (R=0.32; P<0.01). In lesions of patients with low CRP, a greater rate of discrepancy was found, as 100% of lesions in patients with DM versus 66.1% of lesions of patients without DM had a high DeltaT in one or both lesions (P<0.01). CONCLUSION: In patients with DM, local inflammatory activation is diffuse and correlates with systemic inflammation. However, low systemic inflammatory activation does not always predict an increase in local thermal heterogeneity.

Asymmetric dimethylarginine (ADMA) and other endogenous nitric oxide synthase (NOS) inhibitors as an important cause of vascular insulin resistance.

Asymmetric dimethylarginine (ADMA) and NG-monomethyl- L-arginine ( L-NMMA) are important endogenous endothelial nitric oxide synthase (eNOS) inhibitors. Studies have shown that patients with insulin resistance have elevated plasma levels of ADMA. Moreover, ADMA levels have a prognostic value on long-term outcome of patients with coronary artery disease. Insulin resistance, a disorder associated to inadequate biological responsiveness to the actions of exogenous or endogenous insulin, is a metabolic condition, which exists in patients with cardiovascular diseases. This disorder affects the functional balance of vascular endothelium via changes of nitric oxide (NO) metabolism. Nitric oxide is produced in endothelial cells from the substrate L-arginine via eNOS. Elevated ADMA levels cause eNOS uncoupling, a mechanism which leads to decreased NO bioavailability and increased production of hydrogen peroxide. According to clinical studies, the administration of L-arginine to patients with high ADMA levels improves NO synthesis by antagonizing the deleterious effect of ADMA on eNOS function, although in specific populations such as diabetes mellitus, this might even been harmful. More studies are required in order to certify the role of NOS inhibitors in insulin resistance and endothelial dysfunction. It is still difficult to say whether increased ADMA levels in certain populations is only a reason or the result of the molecular alterations, which take place in vascular disease states.

Interaction between cytokines and sCD40L in patients with stable and unstable coronary syndromes.

BACKGROUND: Evidence suggests that soluble CD40-ligand (sCD40L) is elevated in coronary artery disease (CAD) and is released from activated platelets during the acute myocardial infarction (AMI). Although sCD40L is part of immune response, the mechanisms regulating its release in different disease states remain unknown. MATERIALS AND METHODS: This study enrolled 596 subjects: 201 patients with stable CAD, 109 patients with AMI and 286 healthy controls. Circulating levels of sCD40L, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-a (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with AMI (n = 109) had higher levels of sCD40L and IL-6 compared to both CAD (n = 201) (P < 0.01) and controls (n = 286) (P < 0.01), while CAD also had higher levels of sCD40L and IL-6 compared to controls (P < 0.01). Similarly, sICAM-1 and sVCAM-1 levels were higher in CAD and AMI compared to controls (P < 0.05). IL-6 was the only parameter independently associated with sCD40L in healthy individuals [beta (SE):0.491(0.096), P = 0.0001]. However, in CAD or AMI, only diabetes mellitus [beta (SE): 2.689 (1.082), P = 0.044 and beta (SE): 10.406 (3.215), P = 0.002, respectively] and smoking [beta (SE): 3.470 (1.111), P = 0.002 and beta (SE): 9.694 (2.478), P = 0.0001, respectively] (but not IL-6), were independently associated with sCD40L levels. CONCLUSIONS: Both CAD and AMI are accompanied by increased levels of sCD40L in parallel with an elevation of proinflammatory cytokine IL-6 and adhesion molecules sVCAM-1 and sICAM-1. Diabetes mellitus and smoking (but not IL-6 or adhesion molecules) were the only factors independently associated with sCD40L levels in CAD and AMI patients.

Stents covered by an autologous arterial graft in porcine coronary arteries: feasibility, vascular injury and effect on neointimal hyperplasia.

OBJECTIVE: The use of stents has improved results after balloon coronary angioplasty. Several materials have been proposed for covering the metallic surface of the stent to reduce the rate of subacute thrombosis and restenosis. In our institution, an autologous arterial graft was used for covering the external surface of a conventional stent. The angiographic and histological response in a porcine coronary artery model was investigated. METHODS: An autologous arterial graft was removed from the femoral artery and carefully prepared. Subsequently, a conventional stent was covered externally by the arterial graft. Twenty-two covered stents and 22 uncovered regular stents were implanted alternatively in the coronary arteries of 22 pigs. One animal died immediately after the procedure, due to thrombus formation in the uncovered stent. Six animals were sacrificed at seven days and the remaining animals were sacrificed at two months. Before the sacrifice, coronary angiography was performed in all animals. RESULTS: Thrombosis was detected in two control segments and in one covered stented segment. After seven days, the luminal surface of the covered stents was covered by a new endothelial layer in contrast to partial endothelial cell appearance in the control group. The angiographic parameters were similar between the two groups. Histologically, the covered stents were associated with less vascular injury compared to uncovered stents. In covered stents a trend towards reduction of maximal intimal hyperplasia was detected (covered: 116.6 +/- 47.75 vs uncovered: 150.25 +/- 46.81 microns, p = 0.08); also the thickness of the arterial media was reduced (covered: 21.34 +/- 10.28 vs uncovered: 102.63 +/- 18.71 microns, p = 0.02). The luminal and vessel areas were similar in the two groups. CONCLUSIONS: The preparation and implantation of the autologous arterial graft-covered stent is technically safe and feasible. This type of covered stent results in accelerated endothelialization, less vascular injury, thinning of the arterial media and a trend to reduce the intimal hyperplasia in normal coronary arteries.

Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo: A new method of detection by application of a special thermography catheter.

BACKGROUND: Activated macrophages play an important role in the pathogenesis of acute ischemic syndromes. It has been postulated that detection of heat released by activated inflammatory cells of atherosclerotic plaques may predict plaque rupture and thrombosis. Previous ex vivo studies have shown that there is thermal heterogeneity in human carotid atherosclerotic plaques. METHODS AND RESULTS: To measure the temperature of human arteries in vivo, we developed a catheter-based technique. Ninety patients (45 with normal coronary arteries, 15 with stable angina [SA], 15 with unstable angina [UA], and 15 with acute myocardial infarction [AMI]) were studied. The thermistor of the thermography catheter has a temperature accuracy of 0.05 degrees C, a time constant of 300 ms, and a spatial resolution of 0.5 mm. Temperature was constant within the arteries of the control subjects, whereas most atherosclerotic plaques showed higher temperature compared with healthy vessel wall. Temperature differences between atherosclerotic plaque and healthy vessel wall increased progressively from SA to AMI patients (difference of plaque temperature from background temperature, 0. 106+/-0.110 degrees C in SA, 0.683+/-0.347 degrees C in UA, and 1. 472+/-0.691 degrees C in AMI). Heterogeneity within the plaque was shown in 20%, 40%, and 67% of the patients with SA, UA, and AMI, respectively, whereas no heterogeneity was shown in the control subjects. CONCLUSIONS: Thermal heterogeneity within human atherosclerotic coronary arteries was shown in vivo by use of a special thermography catheter. This heterogeneity is larger in UA and AMI, suggesting that it may be related to the pathogenesis.