Ultrasensitive C-reactive Protein Research Articles

Early markers for atherosclerosis and metabolic syndrome in children

The high prevalence of obesity in children favors the appearance of metabolic syndrome (MS), increasing their cardiovascular risk. To evaluate components of MS in children and to correlate them with surrogate markers of atherosclerosis and subclinical inflammation. We studied 209 children aged 11.5 +/- 2 years (50% girls, 30% prepuberal). Fifty percent had normal weight, 18% were overweight, 29% were obese and 3% were undernourished. A fasting blood sample was obtained to measure lipid levels, glucose, insulin, adiponectin and ultrasensitive C-reactive protein (usCRP). Subclinical atherosclerosis was evaluated using flow mediated dilatation of brachial artery (FMD) and carotid intima-media thickness (IMT). For diagnosis of MS we adapted Cook's criteria. Five percent of all children and 18% of those with overweight had MS. Children with more components had significantly higher fasting insulin and Homeostasis Model Assessment (HOMA) values. Clustering of MS components was also associated to higher values of usCRP and non significantly to lower adiponectin levels. We did not find differences in FMD. In obese children there was a tendency towards a higher IMT with clustering of MS components, although not significant. Children with overweight presented a higher risk of a clustering of MS components, which was also associated with insulin resistance and increase in ultrasensitive C reactive protein.

Marcadores de aterosclerosis temprana y síndrome metabólico en niños

The high prevalence of obesity in children favors the appearance of metabolic syndrome (MS), increasing their cardiovascular risk.To evaluate components of MS in children and to correlate them with surrogate markers of atherosclerosis and subclinical inflammation.We studied 209 children aged 11.5 +/- 2 years (50% girls, 30% prepuberal). Fifty percent had normal weight, 18% were overweight, 29% were obese and 3% were undernourished. A fasting blood sample was obtained to measure lipid levels, glucose, insulin, adiponectin and ultrasensitive C-reactive protein (usCRP). Subclinical atherosclerosis was evaluated using flow mediated dilatation of brachial artery (FMD) and carotid intima-media thickness (IMT). For diagnosis of MS we adapted Cook's criteria.Five percent of all children and 18% of those with overweight had MS. Children with more components had significantly higher fasting insulin and Homeostasis Model Assessment (HOMA) values. Clustering of MS components was also associated to higher values of usCRP and non significantly to lower adiponectin levels. We did not find differences in FMD. In obese children there was a tendency towards a higher IMT with clustering of MS components, although not significant.Children with overweight presented a higher risk of a clustering of MS components, which was also associated with insulin resistance and increase in ultrasensitive C reactive protein.

Preatherosclerosis and Adiponectin Subfractions in Obese Adolescents

We evaluated total adiponectin, high-molecular weight (HMW), medium-molecular weight (MMW), low-molecular weight (LMW) adiponectin subfractions, clinical parameters, routine lab parameters, lipids, metabolic, inflammatory biomarkers, and intima-media thickness (IMT) of common carotid arteries in 70 obese juveniles and adolescents with preatherosclerosis and 55 normal weight controls of similar age and gender distribution. Compared with the controls, the obese probands had a significantly increased IMT (P < 0.001) and elevated ultra-sensitive C-reactive protein (P < 0.001) indicating early vascular burden. Total and HMW adiponectin were significantly decreased in the obese cohort. The ratio between HMW and total adiponectin was significantly decreased in obese probands whereas the LMW/total adiponectin ratio was increased. Overall, total-, HMW, and MMW adiponectin were significantly negatively correlated with carotid IMT. The HMW/total adiponectin ratio correlated significantly negatively, and the LMW/total adiponectin ratio significantly positively with the IMT. Furthermore, HMW adiponectin was significantly positively correlated with high-density lipoprotein (HDL)-cholesterol and serum apolipoprotein A1, and negatively with BMI, triglycerides, homeostatic model assessment (HOMA)-index, leptin, liver transaminases, and uric acid. This remained stable after controlling for gender. Multiple regression analysis of body measures and all other lab parameters showed the strongest correlation between HMW adiponectin and carotid IMT (beta = -0.35, P < 0.001). Taken together, our study provides the first evidence that preatherosclerosis in obese juveniles and adolescents is associated with altered subfractions of adiponectin, whereas after multiple testing the HMW subfraction showed a better correlation to IMT compared with total adiponectin.

Altered plasma adipokines and markers of oxidative stress suggest increased risk of cardiovascular disease in First Nation youth with obesity or type 2 diabetes mellitus

To evaluate cardiovascular disease risk in First Nation youth with and without type 2 diabetes mellitus (T2DM) or obesity by comparing pro- and anti-inflammatory adipokines, markers of oxidative stress and the plasma phospholipid fatty acid profile. Self-declared First Nation youth (12-15 yr) with T2DM (n = 24) as well as age-, gender-, and body mass index-matched controls (obese group; n = 19) and unmatched controls (control group; n = 34) were recruited from a pediatric diabetes clinic. Plasma tumor necrosis factor-alpha, ultrasensitive C-reactive protein, resistin, and total antioxidant status were not different among the three groups. Plasma total leptin, soluble leptin receptor, and free leptin were significantly higher in the T2DM group than the control group (p < 0.001, p = 0.019, p < 0.001, respectively) but did not differ from the obese group. Similarly, oxidized low-density lipoprotein was higher in the T2DM group compared with controls (p = 0.002) but not in the obese group. However, interleukin-6 was significantly higher (p < 0.001) in the T2DM group compared with both the control and the obese groups, suggesting that T2DM, but not an increase in adiposity, was responsible for this elevation. Adiponectin was significantly lower in the T2DM group compared with the control group only (p = 0.035). Changes in plasma adipokines and oxidative stress can already be detected in youth with T2DM; however, many of the changes are mirrored in obese youth, suggesting that both these populations are at an increased risk for future cardiovascular complications.

Increased carotid artery intima-media thickness following venoarterial extracorporeal membrane oxygenation in the neonatal period

To compare left carotid intima-media thickness (CIMT) and biochemical markers for atherogenesis in neonatal venoarterial extracorporeal membrane oxygenation (ECMO) survivors with normal controls during childhood. Venoarterial ECMO survivors and healthy patients between 12 and 18 years of age were enrolled in a matched control prospective study. ECMO survivors were matched to controls based on chronological age and percentage of body mass index (BMI). Measured CIMT of the posterior left carotid artery and CIMT values corrected for carotid artery size were used for data analysis. Thirty-one neonatal venoarterial ECMO survivors were matched to 31 healthy controls. No significant differences were found between ECMO survivors and controls for age, weight, percentage of BMI, total fat composition, lipid profiles, ultrasensitive C-reactive protein or homocysteine levels. Significant differences between ECMO and controls patients were found in systolic, diastolic and mean left CIMT. Compared with controls, the thickness of the left carotid intima media is significantly increased at the age of 12 to 18 years in neonatal venoarterial ECMO survivors. The clinical significance of this increased CIMT is unknown. ECMO centers may want to incorporate assessment of CIMT in their follow-up protocols.

Changes in HDL Cholesterol and in the Inflammatory Markers of Atherogenesis After an Oral Fat Load in Type-2 Diabetic Patients and Normal Individuals

Type-2 diabetic patients exhibit postprandial hypertriglyceridemia, a risk factor for atherosclerosis. Several inflammatory markers are also risk factors for atherosclerosis, such as ultrasensitive C-reactive protein (CRP) and number of leukocytes. There is a relationship between the increase in triglycerides and that of leukocytes in the postprandial period. Our objective was to evaluate whether the lipid changes in the postprandial period are related to changes in the inflammatory markers of atherogenesis in type-2 diabetic patients. Lipids, ultrasensitive CRP, and leukocyte count were analyzed during fasting and after a meal containing 56 g of fat. There was a decrease in HDL-cholesterol at five hours in the control group and at three and five hours in the diabetic group, and an increase in triglycerides at both three and five hours in the two groups, the latter being more evident at five hours in the diabetic patients. The decrease in HDL-cholesterol in the diabetic patients was inversely proportional to waist circumference, waist hip ratio, and body mass index (BMI). The number of leukocytes showed an increase in both groups at both times, being more apparent at five hours. There were no differences in lipids or markers between the groups. The fall in postprandial HDL-cholesterol correlated with visceral obesity in the group with type-2 diabetes. Hypertriglyceridemia and lowered HDL-cholesterol in the postprandial period were accompanied by a rise in the number of leukocytes in both healthy and type-2 diabetic subjects.

The Effects of Liposuction Removal of Subcutaneous Abdominal Fat on Lipid Metabolism are Independent of Insulin Sensitivity in Normal-Overweight Individuals

Abdominal fat (both visceral and subcutaneous) accumulation is associated with an increased risk of developing insulin resistance. The latter stands as the basis upon which diabetes, hypertension, and atherogenic dyslipidemia tend to build up. Hence, abdominal liposuction (AL) could theoretically hold metabolic benefits. We undertook the present study to assess the effects of AL on carbohydrate and lipid metabolism. This is a prospective study including 20 healthy volunteers (M2/F18) aged 39.6 +/- 7.7 years old (24-52), body mass index (BMI) = 25.3 +/- 4.7 kg/m(2) (19.8-36) who underwent AL. Before and 4 months after AL, we measured glucose and insulin concentrations, HOMA index [glucose (mM) x IRI (microUI/l)/22.5], free fatty acids (FFA), glycerol, total cholesterol and triglycerides, high-density lipoprotein (HDL)-cholesterol (HDL-c), low-density lipoprotein (LDL)-cholesterol (LDL-c), very low-density lipoprotein (VLDL)-cholesterol (VLDL-c) and apolipoproteins (apo) B, AI and AII, adiponectin (Adp), and ultra-sensitive C-reactive protein (CRP). Lipo-aspirate averaged 5.494 +/- 5.297 cc (600-19.000). Weight, BMI, and waist circumference decreased significantly 4 months after surgery by 4.6, 4.6 and 5.9%, respectively. There were significant decrements in FFA (-35%, p < 0.0001), glycerol (-63%, p < 0.0005), VLDL-c (-15.2%; p < 0.001), and triglycerides (-21.3%, p < 0.002), an increase in HDL-c (+10%, p < 0.03), Apo AI (+10.1%, p < 0.02), and Apo AII (+11.8%, p < 0.001). Total cholesterol, LDL-c, ApoB, and the LDL-c/ApoB ratio raised by +15% (p < 0.0005), +27.3% (p < 0.000), +15.1% (p < 0.008) and +2.76% (p < 0.008), respectively. Glucose, insulin, the HOMA index, Adp, and CRP were not significantly altered after AL. AL in healthy normal weight or slightly overweight subjects improves the major lipoprotein components of obesity-associated dyslipidemia. This improvement occurs independent of insulin sensitivity.

The effect of transdermal estradiol or oral conjugated oestrogen and fenretinide versus placebo on haemostasis and cardiovascular risk biomarkers in a randomised breast cancer chemoprevention trial

Background:We have previously reported the favourable effect of transdermal estradiol (E2), relative to oral conjugated equine oestrogen (CEE), on ultrasensitive C-reactive protein after 12 months of treatment in a retinoid-placebo controlled two-by-two randomized breast cancer prevention trial (Decensi A et al (2002) Circulation 106 10 1224–8). Here, we investigate the changes in lipids and clotting profile in patients of the same trial.Methods and results:Recent post-menopausal women were randomised to either oral CEE 0.625 mg/day and placebo (n = 55), CEE and fenretinide 200 mg/day (n = 56), transdermal E2 50 mg/day and placebo (n = 59) or E2 and fenretinide 200 mg/day (n = 56). Sequential medroxyprogesterone acetate 10 mg/day was given in each group. After 12 months, there was a statistically significant effect of the route of administration of hormone replacement therapy (HRT) on fibrinogen levels; the median percentage change being −5.7% with CEE and −1.1% with E2 (p = 0.012). Total cholesterol decreased in all arms (p < 0.0001). HDL-C decreased significantly with transdermal E2 (p = 0.006) compared to oral CEE and with fenretinide relative to placebo (p<0.001). Triglycerides exhibited an opposite modulation in the HRT route, with a 21.4% median increase with oral CEE and an 8.6% reduction with transdermal E2 (p < 0.0001). Antithrombin-III showed a 4% borderline significant reduction in the fenretinide arm relative to placebo, irrespective of the HRT administration route (p = 0.055).Conclusions:Our data indicate that transdermal E2 may be preferable to oral CEE based on its safer cardiovascular risk profile. Fenretinide modified some cardiovascular risk biomarkers and confirmed a safer profile compared to other retinoids.

Relationship between abnormal glycometabolism and ultra-sensitive C-reactive protein in non-alcoholic fatty liver

Relationship between abnormal glycometabolism and ultra-sensitive C-reactive protein in non-alcoholic fatty liver

P368 IS HBA1C CORRELATED TO RESTING ENERGY EXPENDITURE IN TYPE 2 DIABETIC PATIENTS? A PILOT STUDY

leptin, ultrasensitive CRP (usCRP), IL1-beta, IL6, TNFalpha and homocystein prior and after treatment. Results: In the whole group we founded a decrease in ALT levels in 43 patients (58.10%) reaching normal levels only in 22 (29.72%). There was a decrease in HOMA-IR, PCRus, IL-6, homocystein and ferritin, reaching statistical significance only in leptin levels (1.99±2.21 vs 1.05±1.12; p = 0.023) observed in 53 patients (71.62%). Analyzing pre-treatment ALT elevated levels patients subgroup we founded a significant decrease in HOMA-IR in those that reach normal levels in contrast with those with persistent elevated ALT levels (4.23±2.83, 2.36±1.19, 4.07±3.72; p = 0.02), accompanied of a significant decrease TNFalpha (6.80±1.61, 4.67±1.28, 6.82±2.66; p = 0.007). We had similar results regarding to TNF-alpha in patients with elevated pre-treatment HOMA-IR that reach normality (6.80±1.61, 4.06±1.5, 7.56±0.80; p = 0.04). In spite of a decrease in other proinflammatory factors level after 6mo of treatment in this subgroup, they not reach statistical significance. We not observed significant decrease in patients with normal pre-treatment ALT or HOMA-IR <3.9. Conclusion: After 6 mo of integral treatment of patients with NAFLD, persisted a proinflammatory state in spite of a decrease in insulin-resistance (HOMA-IR) and factors related. This decrease reached statistical significance in patients with pre-treatment elevated ALT levels that normalised them, reinforcing a role HOMA-IR and TNFalfa in such elevated levels.

Actualités en hémodialyse

Dialysis is a complement to or a substitute for renal transplantation. Mortality of dialysis patients remains too high - 9-22%/year - and is associated above all with old age and comorbidities but also with the quantity and quality of hemodialysis. Hemodialysis must be more personalized, with a possible increase in its frequency (daily) or in the duration of sessions (longer than 4.5 h). Chronic inflammation, present in 30% of patients, is a source of morbidity and mortality. It must be detected by ultrasensitive CRP (C-reactive protein) assays and its cause sought and treated. Metabolism of phosphate and calcium is too often inadequately controlled, despite the contribution of new very active molecules. The resultant vascular calcifications are an important cardiovascular risk factor. Progress in dialysis techniques also plays a role in improving quality of life and life span: use of highly permeable membranes, ultrapure dialysate, closed-loop biofeedback volume control, and maintenance of thermal balance.

Proteína C reactiva y su relación con adiposidad, factores de riesgo cardiovascular y aterosclerosis subclínica en niños sanos

In adults, C-reactive protein is a marker of cardiovascular risk. It is associated with both classical and metabolic risk factors and is a predictor of cardiovascular events. The aim was to investigate the relationship of the C-reactive protein concentration to classical cardiovascular risk factors, measures of adiposity subclinical atherosclerosis in children. The values of traditional risk factors, anthropometric parameters, fasting lipids, glucose and C-reactive protein levels were recorded. In addition, the carotid artery intima-media thickness was measured, and brachial artery endothelial function was assessed using flow-mediated dilation. The study included 112 children (58 male) with a mean age of 11.3+/-1.9 years. The mean C-reactive protein concentration was 0.9+/-1.5 mg/L. In males, there were significant direct correlations between the C-reactive protein concentration and body mass index, total fat mass, central adiposity, waist circumference, and low-density lipoprotein (LDL) cholesterol level. In females, C-reactive protein was associated with only body mass index. Boys in the highest C-reactive protein tertile had a significantly higher body mass index, total fat mass, LDL cholesterol level, and waist circumference. In the whole group, the best predictor of an elevated ultrasensitive C-reactive protein concentration was the body mass index (odds ratio=2.04 [1.30-3.21]). No relationship was found between the C-reactive protein concentration and the percentage flow-mediated dilation of the brachial artery or the carotid intima-media thickness. The results indicate that, in children, there is a significant direct relationship between the ultrasensitive C-reactive protein concentration and measures of adiposity, particularly body mass index. However, no relationship between C-reactive protein and subclinical atherosclerosis was observed.

Correlação entre os níveis de proteína C reativa ultra-sensível e as características clínicas e laboratoriais em mulheres com síndrome do ovário policístico

OBJETIVO: avaliar a concentração plasmática da proteína C reativa ultra-sensível (PCRus) e a sua correlação com variáveis clínicas, hormonais e metabólicas em pacientes portadoras da síndrome do ovário policístico (SOP). Métodos: estudo transversal, que incluiu 46 pacientes portadoras de síndrome do ovário policístico, diagnosticadas segundo os critérios de Rotterdam (2003), e 44 pacientes controle, que foram submetidas a dosagem da PCRus. O índice de massa corporal (IMC), a idade, a circunferência abdominal e os níveis de insulina de jejum, de testosterona, do HOMA-IR (homeostasis model assessment-insulin resistance) e do colesterol total, além de frações foram correlacionados aos níveis de PCR, utilizando-se análise de regressão multivariada. RESULTADOS: as portadoras da SOP apresentavam idade, IMC, circunferência abdominal, insulina de jejum, HOMA-IR, colesterol total e lipoproteína de baixa densidade (LDL) em concentrações plasmáticas superiores às do controle. Houve diferença significante nos níveis da PCRus entre o grupo da SOP (2,7±2,17 mg/dL) e o controle (1,6±1,49 mg/dL), p<0,05. Quando os níveis da PCRus foram categorizados em baixo (<1,0 mg/L), médio (1-3,0 mg/L) e elevado (3,0 mg/L) risco cardiovascular, 28,3% das portadoras da SOP apresentaram níveis da PCRus para baixo risco, 34,8% para médio e 37% para elevado risco cardiovascular. A prevalência da síndrome metabólica foi mais elevada entre as portadoras da SOP (30,4%), quando comparadas ao grupo controle (6,8%). Após o ajuste das variáveis de confusão, por um modelo de regressão linear multivariada stepwise, a presença da SOP mostrou efeito independente das outras variáveis sobre os níveis da PCRus. CONCLUSÕES: os níveis da PCRus foram mais elevados nas mulheres portadoras da SOP. A SOP tem efeito independente na determinação dos níveis plasmáticos da PCR.

Association Among C-Reactive Protein, Fatty Liver Disease, and Cardiovascular Risk

Nonalcoholic fatty liver disease (NAFLD) is associated with several metabolic disturbances involving inflammation. Ultrasensitive C-reactive protein (uCRP), a marker of coronary heart disease and other chronic diseases, has not been investigated in NAFLD. We tested the relationship between uCRP and NAFLD in middle-aged asymptomatic subjects, independently of other metabolic disturbances associated with metabolic syndrome and cardiovascular risk. We compared 310 subjects with steatosis visible on ultrasound (cases) with 630 and without (controls). Body mass index (BMI), blood pressure and serum levels of uCRP, glucose, lipids, and lipoproteins were measured in all subjects. Differences between groups and the impact of serum uCRP levels were tested by univariate and multivariate logistic regression analysis. Cases were statistically different from controls in the frequency of metabolic syndrome (66.4% vs. 26.7%; P < 0.001). Cases were significantly older (P < 0.001), and had significantly higher values for BMI, glucose, total cholesterol and triglycerides (P < 0.001), and mean uCRP concentrations (4.5 vs. 2.79 mg/L; P < 0.001). By univariate analysis, variables significantly associated with cases were glucose (OR, 4.09; 95% CI, 2.98-5.61), BMI (OR 5.54; 95% CI, 4.09-7.49), and uCRP (OR 7.06; 95% CI, 4.51-11.02). By multivariate analysis, uCRP levels were associated with hepatic steatosis (OR 5.83; 95% CI, 3.07-11.06). Cardiovascular risk was also higher in subjects with NAFLD (4.7 vs. 2.8). Subjects with hepatic steatosis showed an increased concentration of uCRP independently of other metabolic disturbances; this suggests an increased risk of cardiovascular diseases and could be used as a marker of chronic inflammation.

Prevalencia del síndrome metabólico en la provincia de Albacete

The primary objective of this study was to determine the prevalence of Metabolic Syndrome (MS) in people between 40-70 years of age in the province of Albacete (Spain).A population-based, cross-sectional study was made of people between 40-70 years of age in three representative municipalities of the province of Albacete. A total of 425 subjects were included, with a mean age of 53.1 years (95% CI: 52.3-54). Women represented 50.4% of the series and males 49.6%. All participants were subjected to general laboratory testing, physical examination and the measurement of anthropometric parameters. MS was defined according to the ATP-III criteria. Prevalence of MS and its distribution according to the different epidemiological characteristics were calculated.Total prevalence of MS was 20.9% (88/421), with a mean age of 57 years (95% CI: 55.1-59). Prevalence was seen to increase with age, reaching up to one-third of all subjects over 60 years. Significant differences were observed in relationship to a background of ischemic heart disease, ultrasensitive C-reactive protein elevation and the detection of microalbuninuria in MS subjects. Arterial hypertension and abdominal obesity were the most prevalent criteria in MS subjects.Taking into consideration the important co-morbidity of MS, knowledge of the prevalence and characteristics of the syndrome in our setting and its early identification and intervention targeted to the different factors underlying MS will contribute to reduce the number of cardiovascular events associated with the syndrome.

CHILDHOOD CAROTID INTIMA MEDIAL THICKNESS FOLLOWING VENOARTERIAL NEONATAL EXTRACORPOREAL MEMBRANE OXYGENATION: EVIDENCE OF CARDIOVASCULAR DISEASE?

Background As of 2006, the Extracorporeal Life Support Organization registry reported 11,786 neonatal venoarterial (VA) extracorporeal membrane oxygenation (ECMO) survivors with their right carotid artery ligated for the procedure. Objective To compare left carotid intima medial thickness (CIMT) and biochemical markers for atherogenesis in VA ECMO survivors to normal controls. Methods Children9s Hospital Los Angeles VA ECMO survivors and healthy subjects born before 1994 were invited to participate in a matched control prospective study. ECMO survivors were matched to controls based on chronological age and percentile body mass index (%BMI). Using a high-resolution B-mode carotid ultrasonography and a 15 MHz transducer, visualization of the carotid arterial wall was obtained according to the method of Hodis et al by a trained sonographer blinded to the status of the participants (patient vs control). An automated computerized edge detection software measured CIMT from the far wall of the left carotid artery. Lipid profiles, ultrasensitive CRP, ferritin, and homocystine levels were also collected. Results Thirty-one VA ECMO survivors were matched to 31 healthy controls. No significant differences were found between ECMO survivors and controls for age (16.8 ± 0.3 vs 16.2 ± 0.3 years), weight (68.5 ± 3.3 vs 69.8 ± 2.9 kg), %BMI (73.5 ± 5.2 vs 73.5 ± 5.3%), total fat composition, lipid profiles, ultrasensitive CRP, ferritin, or homocystine levels. Significant differences between ECMO and controls subjects were found in measurements of systolic left CIMT (0.42 ± 0.01 vs 0.39 ± 0.01 mm; p = .03) and mean (systolic-diastolic) left CIMT (0.40 ± 0.01 vs 0.38 ± 0.01 mm; p = .04). Conclusion VA ECMO survivors, between 12 and 20 years of age, have a significant increase in left systolic and mean CIMT compared with controls. Due to their dependence on left carotid blood flow to maintain adequate cerebral perfusion, VA ECMO patients may be at risk of significant cardiovascular disease in adulthood. Further studies need to focus on the pathogenesis of intimal thickening and on cardiovascular evaluation of VA ECMO survivors into adulthood.

Changes of osteoprotegerin before and after insulin therapy in type 1 diabetic patients

Objective Osteoprotegerin (OPG) regulates osteoclast and immune functions and appears to represent a protective factor for vascular system. However, the role of OPG in endothelial dysfunction of type 1 diabetic patients has not been evaluated. The purpose of this study was to investigate the relationship between plasma OPG levels and endothelium-dependent arterial dilation in type 1 diabetic patients. Research design and methods This study subjects included 22 newly diagnosed type 1 diabetic patients and 28 healthy subjects. All patients were then given insulin therapy for 6 months. Plasma OPG concentration was measured in duplicate by a sandwich ELISA method, and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia and after sublingual glyceryltrinitrate (GTN). Results Plasma OPG level in patients before treatment was 3.09 ± 0.70 ng/L, which was significantly higher than that in control (2.07 ± 0.75 ng/L) ( p < 0.001). After 6 months treatment, OPG levels decreased markedly (2.58 ± 0.59 ng/L) ( p < 0.001). The flow-mediated endothelium-dependent arterial dilation in patients before treatment was 3.35 ± 0.67%, which was significantly lower than that in control (5.17 ± 0.83%) ( p < 0.001), and improved markedly after 6 months treatment (4.27 ± 0.63%) ( p < 0.001). In multivariate analysis, OPG was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and ultra sensitive C-reactive protein (CRP) at baseline ( p < 0.01). The absolute changes in OPG showed significant correlation with the changes in endothelium-dependent arterial dilation, FBG, HbA1c, and CRP in diabetic patients during the course of treatment ( p < 0.01). Conclusion This study shows that plasma OPG levels are elevated in newly diagnosed type 1 diabetic patients, and that plasma OPG levels are significantly associated with endothelial function.

Characteristics of subclinical inflammation in uncomplicated arterial hypertension

Objective. Inflammation and oxidative stress are important determinants for target organ damage in arterial hypertension. The aim of the study was to evaluate inflammatory and oxidative markers in uncomplicated arterial hypertension. Methods. Study population included 114 (59 male, age 30-65 years) untreated hypertensive non-diabetic patients without associated clinical conditions. Plasma concentrations of malonic dyaldehyde and SH-groups were evaluated as oxidative stress markers. Serum concentrations of ultrasensitive CRP, TNF-α, interleukins (IL) lß, 4 and 6 were measured. Correlation between oxidative stress, inflammatory markers, blood pressure and traditional risk factors was analyzed. Results. In 45% patients elevation at leas of one pro-inflammatory cytokine was found. In 26,3% this elevation was revealed together with low anti-inflammatory ration (IL-4/IL-6), in 18,4% - with high IL-4/IL-6. In 55% concentration of all pro-inflammatory cytokines was lower than median. In one third of patients low cytokines levels were observed together with low IL-4/IL-6, in 22% - with high IL-4/IL-6. Regression analysis revealed that inflammatory and oxidative status are unrelated to gender, age and determined by diastolic blood pressure, smoking, dyslipidemia and rennin-angiotensine system activity. Conclusion. In untreated hypertensive non-diabetic patients High levels of pro-inflammatory cytokines may coexist either with low or high intiinflammatory ratio of IL-4/IL-6. Inflammatory and oxidative status are determined haemodynamic load, smoking, dyslipidemia and rennin-angiotensine system activity.

The Relationship Between Plasma Osteoprotegerin and Endothelium-Dependent Arterial Dilation in Type 2 Diabetes

Osteoprotegerin is a recently identified inhibitor of bone resorption. Recent studies indicate that osteoprotegerin also acts as an important regulatory molecule in the vasculature. The purpose of this study was to investigate the relationship between plasma osteoprotegerin levels and endothelium-dependent arterial dilation in type 2 diabetic patients. The study subjects included 40 newly diagnosed type 2 diabetic patients and 46 healthy subjects. All patients were given insulin therapy for 6 months. Plasma osteoprotegerin concentration was measured in duplicate by a sandwich enzyme-linked immunosorbent assay method, and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual glyceryltrinitrate. The plasma osteoprotegerin level in patients before treatment was 3.36 +/- 0.32 ng/l, which was significantly higher than that in control subjects (2.38 +/- 0.25 ng/l, P < 0.001). After 6 months of treatment, osteoprotegerin levels decreased markedly (2.83 +/- 0.34 ng/l, P < 0.001). Flow-mediated endothelium-dependent arterial dilation in patients before treatment was 3.21 +/- 0.52%, which was significantly lower than that in control subjects (4.46 +/- 0.56%, P < 0.01), and it improved markedly after 6 months of treatment (4.03 +/- 0.49%, P < 0.01). In multivariate analysis, osteoprotegerin was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), HbA(1c) (A1C), and ultrasensitive C-reactive protein (CRP) at baseline (P < 0.01). The absolute changes in osteoprotegerin showed significant correlation with changes in endothelium-dependent arterial dilation, FBG, A1C, and CRP in diabetic patients during the course of treatment (P < 0.01). This study shows that plasma osteoprotegerin levels are elevated in newly diagnosed diabetic patients and are significantly associated with endothelial function.

No effect of homocysteine‐lowering therapy on vascular inflammation and haemostasis in peripheral arterial occlusive disease

Although peripheral arterial occlusive disease (PAOD) is significantly associated with elevated homocysteine levels, the clinical relevance of hyperhomocysteinaemia for the prevention and progression of PAOD is still unknown. A total of 65 patients suffering from symptomatic PAOD with elevated homocysteine levels were randomized onto placebo or B-vitamins (50 mg thiaminhydrochlorid, 50 mg pyridoxine, and 0.05 mg cyanocobalamin), plus 5 mg folic acid daily for 6 weeks. Serum levels of folic acid, vitamin B12, creatinine, ultra-sensitive C-reactive protein (usCRP), interleukin (IL)-6, IL-8, IL-18, monocyte-chemo-attractant-protein-1 (MCP-1) and plasma levels of homocysteine, tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were determined on the 1st day and 42nd day. Primary outcome was reduction of homocysteine, secondary outcomes were reduction of usCRP, IL-6, IL-8, Il-18, MCP-1, TF and TFPI. The mean reduction of homocysteine concentration was 33% (95%CI 33.36-55.76, or 18.9+/-5.4 micromol L-1-12.6+/-2.8 micromol L-1, P=0) in the B-vitamin group compared with 1% in the placebo group. Folic acid (P=0) and vitamin B12 (P=0) increased significantly in the verum group, but both remained unchanged in the control group. No treatment effect of lowering of homocysteine on any markers of haemostasis (TF, TFPI) or inflammation (usCRP, IL-6, IL-8, IL-18 and MCP-1) was observed. Although homocysteine is associated with vascular disease risk in the general population and in particular with PAOD, marked lowering of homocysteine concentrations by folic acid and B-vitamin supplementation does not influence inflammatory responses involving usCRP, IL-6, IL-8, IL-18 and MCP-1, nor tissue factor. These results provide evidence against a major effect of hyperhomocysteinaemia on vascular chronic inflammation or coagulation in patients with symptomatic peripheral arterial occlusive disease.