Plasma hsCRP Concentrations Research Articles

Provision of Antioxidant Therapy in Hemodialysis (PATH)

Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy (MHD), and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness. No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress. We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acute-phase inflammation and oxidative stress and improve erythropoietic response in prevalent MHD patients. In total, 353 patients were enrolled in a prospective, placebo-controlled, double-blind clinical trial and randomly assigned to receive a combination of mixed tocopherols (666 IU/d) plus α-lipoic acid (ALA; 600 mg/d) or matching placebos for 6 months (NCT00237718); 238 patients completed the study. High-sensitivity C-reactive protein (hsCRP) and IL-6 concentration were measured as biomarkers of systemic inflammation, and F2 isoprostanes and isofurans were measured as biomarkers of oxidative stress. The groups did not significantly differ at baseline. At 3 and 6 months, the treatment had no significant effect on plasma hsCRP, IL-6, F2 isoprostane, or isofuran concentrations and did not improve the erythropoietic response. No major adverse events were related to the study drug, and both groups had similar mortality and hospitalization rates during the study. In conclusion, the administration of mixed tocopherols and ALA was generally safe and well tolerated, but did not influence biomarkers of inflammation and oxidative stress or the erythropoietic response.

Daily Consumption of Grapefruit for 6 Weeks Reduces Urine F2-Isoprostanes in Overweight Adults with High Baseline Values but Has No Effect on Plasma High-Sensitivity C-Reactive Protein or Soluble Vascular Cellular Adhesion Molecule1–3

Individuals with obesity and metabolic syndrome (MetS) are at increased risk of cardiovascular disease, in part due to heightened inflammatory/oxidative processes. Results from epidemiologic and experimental studies suggest that citrus, and grapefruit in particular, may have a role in promoting vascular health, although clinical trial data are lacking. Here, we evaluated the anti-inflammatory/antioxidant effects of habitual grapefruit consumption in 69 overweight/obese men and women and in a subsample of participants with MetS (n = 29). Participants were randomly assigned to either a grapefruit group in which they consumed a low bioactive diet plus 1.5 grapefruit/d for 6 wk (n = 37, n = 14 with MetS) or to a control condition in which a low bioactive diet devoid of citrus was consumed (n = 32, n = 15 with MetS). Plasma soluble vascular adhesion molecule-1 (sVCAM-1), plasma high-sensitivity C-reactive protein (hsCRP), and urinary F2-isoprostanes were evaluated before and after the intervention phase. F2-isoprostane concentrations were not different in the grapefruit versus control arm after the intervention (12.4 ± 6.4 vs. 15.9 ± 9.0 ng/mg creatinine, P = 0.16), whereas plasma hsCRP concentrations tended to be lower in the grapefruit versus control arm postintervention (2.1 ± 1.5 vs. 2.8 ± 2.0 mg/L, P = 0.09). In adults with MetS, grapefruit consumption tended to result in lower postintervention F2-isoprostane concentrations compared with the control condition (12.0 ± 4.5 vs. 18.3 ± 10.9 ng/mg creatinine, P = 0.06). Furthermore, those with high baseline F2-isoprostane concentrations experienced significant reductions in this biomarker in response to grapefruit consumption (P = 0.021). Change in sVCAM-1 concentrations did not vary by treatment arm nor were there differences between arms postintervention. These results suggest that intake of grapefruit twice daily for 6 wk does not significantly reduce inflammation and oxidative stress, although there is a suggestion of favorable modulation of oxidative stress in overweight and obese adults with MetS or those with high baseline urine F2-isoprostane concentrations.

Plasma levels of high‐sensitive C‐reactive protein do not correlate with inflammatory activity in carotid atherosclerotic plaques

It is well established that subjects with moderately elevated plasma levels of C-reactive protein (CRP) have an increased risk of development of cardiovascular events. As atherosclerosis is a disease characterized by chronic arterial inflammation, it is possible that moderate increases in CRP level reflect the presence of plaque inflammation. To investigate this possibility, we compared plasma levels of hsCRP the day before carotid endarterectomy with the degree of inflammation in the excised plaque tissue. Luminex immunoassays were used to determine the levels of IL-6, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor-α (TNF-α) in plasma and in homogenized plaque tissue from 160 endarterectomy specimens. Plaque sections were stained with antibodies against CD68 to determine the plaque macrophage content. Plasma high-sensitivity (hs)CRP levels were significantly correlated with plasma IL-6 and TNF-α. However, there were no significant associations between plasma hsCRP concentration and plaque cytokine levels or macrophage contents. The present findings strongly argue against hsCRP as a marker of plaque inflammation. Hence, it is more likely that elevated hsCRP is a sign of a subclinical systemic inflammation and this in turn may contribute to progression of cardiovascular disease.

Serum homocysteine and high-sensitive C-reactive protein levels and cardiovascular disease in patients with diabetes mellitus type 2

PURPOSE: Hyperhomocysteinemia and hs-CRP are non-classical risk factors independently associated to the development of cardiovascular disease. The increased coronary heart disease (CHD) risk in subjects with type 2 diabetes mellitus (DMT2) can be in part explained by the classical risk factors like hypertension, hyperlipidemia and obesity. There is no sufficient data about the importance of homocysteine (Hcy) and hs-CRP levels in DMT2 patients without CHD in predicting the macroangiopathic complications. The aim of this study was to determine the association between plasma homocysteine and hs-CRP concentrations in DMT2 patients with and without CHD. MATERIAL AND METHODS: Fifty patients hospitalized in the Clinic of Endocrinology at St. Marina University Hospital of Varna were divided into three groups: group one, 20 DMT2 patients without any evidence of CHD; group two, 20 DMT2 patients with history of CHD and group three, 10 healthy controls matched to these groups in terms of age and classical risk factors for CHD. RESULTS: Serum hs-CRP concentrations were significantly higher in DMT2 patients than in healthy controls as well as in DMT2 patients with CHD than in CHD-free DMT2 ones. Serum Hcy concentrations were significantly higher in DMT2 patient with CHD than in controls. Both markers were elevated in group two presenting with the highest risk for CHD. Scripta Scientifica Medica 2013; 45(1): 58-61.

Analyses of longitudinal effects of gene-environment interactions on plasma C-reactive protein levels: the Hallym Aging Study

High C-reactive protein (CRP) level (above 3 mg/L), an inflammatory biomarker, is a well-known risk factor for cardiovascular disease. We investigated the longitudinal effects of interaction between genetic variants of seven candidate loci (i.e., IL6R, CRP, GCKR, IL6, CYP17A1, HNF1A, and APOE) and eight non-genetic factors (i.e., body mass index (BMI), total cholesterol to high density lipoprotein cholesterol ratio (T/HDL), systolic blood pressure, diastolic blood pressure (DBP), current smoking, alcohol consumption, regular exercise, and sleeping hours) on plasma hsCRP levels in a community-based cohort composed of 1,051 elderly Korean participants with a 6-year follow up. We applied a recently developed nonparametric approach, Survival Dimensionality Reduction (SDR) to evaluate gene-environment interactions using follow up data, and compared the results to those of conventional statistical approaches, Cox proportional hazard (CPH) regression model and log-rank test. Four gene variants significantly interacted with three non-genetic factors: SNPs rs2293571 (GCKR), rs1004467 (CYP17A1) and high DBP (HR = 3.22 and 2.95, P G×E = 0.013 and 0.017, respectively); rs2464196 (HNF1A) and two non-genetic factors, regular exercise (HR = 3.78, P G×E = 0.043) and high T/HDL (HR = 4.54, P G×E = 0.042); and rs439401 (APOE) and regular exercise (HR = 3.01, P G×E = 0.049). The interaction between the rs2464196 and T/HDL was consistently observed in both CPH model and SDR model (Accuracy = 0.86, P = 0.011). Investigating the effects of gene-environment interactions on baseline plasma hsCRP concentrations will provide clues to identify the pathway involved in increasing hsCRP level and the risks of related diseases.

Abstract 18508: The Association of eNOS Gene Single Nucleotide Polymorphism rs1799983 with High-Sensitivity C-Reactive Protein and Early Recurrence of Atrial Fibrillation after Radiofrequency Catheter Ablation

Background: Previous reports have demonstrated the association between single nucleotide polymorphism (SNP) of the eNOS gene and atrial fibrillation (AF). This study evaluated whether eNOS gene variants are associated with high-sensitivity C-reactive protein (hsCRP) and AF recurrence after radiofrequency catheter ablation (RFCA). Methods: A total of 500 consecutive patients (56±11 years, 77% male) with paroxysmal (68%) or persistent (32%) AF who underwent RFCA were included. Plasma hsCRP concentration was measured and SNP of the eNOS gene, rs1799983, was genotyped. A 24- to 48-hour Holter ECG recording was performed at 3, 6, and 12 months after the ablation. Results: When we compared the patients with rs1799983 variant allele (T, n=84) and those without T allele (n=416), rs1799983 variant allele carriers are more likely to have coronary artery disease or stroke (31.0% vs. 17.8%, p=0.004). The early recurrence (ER) of AF (within 3 months) was observed in 31.8%, whereas the clinical recurrence (CR) of AF (after 3 months) occurred in 24.8% of the patients during the median 17 months of follow-up. The patients with ER were more likely to have persistent AF (44.4% vs. 27.1%, p<0.001) and larger left atrium (42.8±6.4 vs. 41.2±6.2 mm, p=0.011) than those without the ER. Although rs1799983 variant was not associated with the CR, carriers of the variant allele had an increased risk of the ER (OR 1.717 for TT+GT vs. GG, 95% CI 1.059-2.785, p=0.028) and experienced recurrence earlier than those without variant allele (11±16 vs. 20±25 days, p=0.016). However, there were no significant differences in hsCRP between variant and non-variant patients (2.32±4.94 vs. 2.06±4.36 mg/L, p=0.618). A multiple logistic regression analysis showed that the rs1799983 variant (OR 1.714, 95% CI 1.045-2.812, p=0.033) and persistent AF (OR 1.905, 95% CI 1.234-2.939, p=0.004) were independent predictors of the ER. Conclusions: The rs1799983 variant of the eNOS gene was associated with early recurrence after RFCA, but not with hsCRP level. A study that further investigates the relationship between genetic variations of eNOS and post-ablation inflammatory process will be warranted.

HS-CRP AND TRADITIONAL RISK FACTORS: WHO IS STILL SIGNIFICANTLY ASSOCIATED WITH DIABETES IN CHINESE OLDEST-OLD?

ObjectivesIncreasingly more studies have shown that high sensitivity C-reactive protein (hs-CRP) is related to diabetes in adults; thus, hs-CRP is thought to be a new emerging risk factor for cardiovascular...

Relationship Between Plasma Neopterin and High Sensitivity C-Reactive Protein Levels and Circadian Rhythm of Blood Pressure in Hypertensive Patients with Obstructive Sleep Apnea Syndrome

To investigate the relationship between plasma neopterin and high sensitivity C-reactive protein (hsCRP) levels and circadian rhythm of blood pressure in hypertensive patients with obstructive sleep apnea syndrome (OSAS). A total of 367 hospitalized hypertensive patients were recruited. They were divided into three groups according to polysomnography (PSG): hypertension alone (group A, n=212), hypertension with mild OSAS (group B, n=107) and hypertension with moderate to severe OSAS (group C, n=48). Plasma neopterin and hsCRP concentrations were measured on or after the day of PSG, and ambulatory blood pressure (ABPM) was monitored in the first week of admission. Plasma neopterin and hsCRP levels were significantly higher in group B and C compared to group A (P<0.05). Incidence of non-dippers was significantly lower in group A (44.5%) compared to group B (67.7%) and C (84.2%) (P<0.05). Nocturnal and diurnal blood pressures were negatively correlated with plasma neopterin and hsCRP. Multiple stepwise regression analysis showed that apnea hypopnea index (AHI), drop rate of systolic blood pressure, mean oxygen saturation (MSaO2), minimum oxygen saturation (SaO2 min) were the main factors for neopterin levels while AHI and MSaO2 were the major factors affecting hsCRP levels. Plasma neopterin and hsCRP levels are increased in hypertensive patients with OSAS and positively correlated with severity of OSAS.

Population-based study of high plasma C-reactive protein concentrations among the Inuit of Nunavik

Background. The shift away from traditional lifestyle in the Inuit population over the past few decades has been associated with an increased prevalence of coronary heart disease (CHD) risk factors such as obesity, high blood pressure (BP) and diabetes. However, the impact of this transition on the pro-inflammatory marker high-sensitivity C-reactive protein (hs-CRP) has not been documented.Objectives. To examine the prevalence of elevated plasma hs-CRP concentrations in Inuit from Nunavik in the province of Quebec (Canada) and identify anthropometric, biochemical and lifestyle risk factors associated with elevated hs-CRP.Design. A population-representative sample of 801 Inuit residents from 14 villages of Nunavik, aged between 18 and 74 years, was included in the analyses. Subjects participated in a clinical session and completed questionnaires on lifestyle. Multivariate logistic regression was used to determine risk factors for elevated hs-CRP.Results. Elevated plasma hs-CRP concentrations (≥2 mg/L) were present in 32.7% (95% confidence interval (CI) 29.5–35.8) of the Inuit adult population and were more prevalent among women than among men (36.7% vs. 29.0%, p=0.007). Multivariate logistic regression analysis indicated that every 1 mmHg increase in systolic BP was associated with a 3% increase in the odds of having hs-CRP concentrations ≥2 mg/L in the Inuit population (95% CI 1.01–1.04). The combination of older age (≥50 vs. <30 years) and elevated waist circumference (gender-specific cut-off values) in a multivariate logistic model was also associated with a 13.3-fold increase in the odds of having plasma hs-CRP concentrations ≥2 mg/L (95% CI 5.8–30.9).Conclusions. These data indicate that elevated hs-CRP is relatively prevalent among Inuit with values that are similar to those seen in Canadian Caucasian populations. Sex, age, waist circumference and systolic BP are major factors that increase the risk of this inflammatory phenotype among Inuit from Nunavik, despite their different lifestyle background compared with Caucasians.To access the supplementary material to this article please see Supplementary files under Article Tools online

The association of hs-CRP with fasting and postprandial plasma lipids in patients with type 2 diabetes is disrupted by dietary monounsaturated fatty acids

The aim of the study was to evaluate whether two dietary approaches recommended for diabetes mellitus and cardiovascular prevention-high-MUFA or complex carbohydrates/fiber-differently influence inflammation. A 4-week crossover study in 12 individuals with type 2 diabetes was performed. Fasting and postprandial hs-CRP plasma levels were not significantly different after a high-carbohydrate/high-fiber/low-glycemic index (CHO/fiber) and a high-MUFA diet. Compared with fasting, hs-CRP levels decreased significantly after the MUFA but not after the CHO/fiber meal. Triglyceride-rich lipoproteins were significantly lower after the CHO/fiber than the MUFA diet. At fasting and postprandially, hs-CRP correlated with triglyceride in whole plasma, chylomicrons, small and large VLDL after the CHO/fiber but not after the MUFA diet. In conclusion, a MUFA-rich diet and a carbohydrate/fiber-rich diet induced similar effects on plasma hs-CRP concentrations. However, these dietary approaches seem to influence hs-CRP levels through different mechanisms. i.e., direct acute postprandial effects by MUFA and triglyceride-rich lipoproteins mediated effects by CHO/fiber.

EGb761, a Ginkgo Biloba Extract, Is Effective Against Atherosclerosis In Vitro, and in a Rat Model of Type 2 Diabetes

BackgroundEGb761, a standardized Ginkgo biloba extract, has antioxidant and antiplatelet aggregation and thus might protect against atherosclerosis. However, molecular and functional properties of EGb761 and its major subcomponents have not been well characterized. We investigated the effect of EGb761 and its major subcomponents (bilobalide, kaemferol, and quercetin) on preventing atherosclerosis in vitro, and in a rat model of type 2 diabetes.Methods and ResultsEGb761 (100 and 200 mg/kg) or normal saline (control) were administered to Otsuka Long-Evans Tokushima Fatty rats, an obese insulin-resistant rat model, for 6 weeks (from 3 weeks before to 3 weeks after carotid artery injury). Immunohistochemical staining was performed to investigate cell proliferation and apoptosis in the injured arteries. Cell migration, caspase-3 activity and DNA fragmentation, monocyte adhesion, and ICAM-1/VCAM-1 levels were explored in vitro. Treatment with EGb761 dose-dependently reduced intima-media ratio, proliferation of vascular smooth muscle cells (VSMCs) and induced greater apoptosis than the controls. Proliferation and migration of VSMCs in vitro were also decreased by the treatment of EGb761. Glucose homeostasis and circulating adiponectin levels were improved, and plasma hsCRP concentrations were decreased in the treatment groups. Caspase-3 activity and DNA fragmentation increased while monocyte adhesion and ICAM-1/VCAM-1 levels decreased significantly. Among subcomponents of EGb761, kaemferol and quercetin reduced VSMC migration and increased caspase activity.ConclusionsEGb761 has a protective role in the development of atherosclerosis and is a potential therapeutic agent for preventing atherosclerosis.

Insulin resistance, low-grade inflammation and type 1 diabetes mellitus

To assess the relationships between insulin resistance and low-grade inflammation in subjects with type 1 diabetes mellitus (T1DM) who do not have clinical macrovascular complications. A total of 120 subjects diagnosed with T1DM 14 years before were evaluated for the following: (1) sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure, smoking, alcohol intake, insulin dose, HbA1c and lipid profile; (2) microvascular complications; (3) plasma concentrations of soluble fractions of tumour necrosis factor-α receptors type 1 and 2, interleukin-6, adiponectin, leptin and high-sensitivity C-reactive protein (hs-CRP); and (4) insulin resistance (estimation of the glucose disposal rate-eGDR). Those subjects with an eGDR below the median of the same sex group were classified as insulin resistant and the others as insulin sensitive. Insulin-resistant men, compared to the insulin-sensitive, had higher WHR (0.89 ± 0.08 vs. 0.83 ± 0.05; P < 0.01), higher systolic [121 (118-125) vs. 114 (108-120) mmHg; P = 0.01] and diastolic [73 (66-80) vs. 67 (70-73) mmHg; P = 0.02] blood pressures, higher HbA1c values [8.7 (8.1-9.9) vs. 7.5 (7.2-8.0) %; P < 0.01] and higher hs-CRP concentrations [1.16 (0.61-3.20) vs. 0.49 (0.31-0.82) mg/dl; P = 0.01], but no other significant differences between groups were found. Insulin-resistant women had higher WHR and HbA1c values, compared to the insulin-sensitive, but they did not have any other differences. In men, hs-CRP correlated significantly with WHR and HbA1c (r = 0.363; P = 0.016 and r = 0.317; P = 0.036, respectively), after adjusting for age, alcohol intake, smoking and microvascular complications. Insulin-resistant men with T1DM have an increase in plasma concentrations of hs-CRP. Central obesity and HbA1c are its main determinants.

High‐Sensitivity C‐Reactive Protein as a Predictor of Atrial Fibrillation Recurrence after Primary Circumferential Pulmonary Vein Isolation

Atrial fibrillation (AF) recurrence after circumferential pulmonary vein isolation (CPVI) is difficult to predict. Inflammation is associated with the development of AF. Inflammatory markers, such as high sensitivity C-reactive protein (hsCRP), are related to AF development via atrial remodeling. However, it is unknown whether plasma hsCRP concentration before CPVI can be used as a predictor for AF recurrence. A total of 121 patients without structural heart disease who underwent primary CPVI by a single operator were included in the study (paroxysmal/persistent AF: 77/44). Left atrial diameter was measured by transesophageal echocardiography. Plasma hsCRP concentration was determined by enzyme-linked immunosorbent assay. Based on the follow-up outcomes, patients were divided into two groups, a recurrence group and a nonrecurrence group. AF recurrence was defined as AF or atrial flutter or atrial tachycardia episodes lasting for ≥30 s during regular follow-up (>12 months). A total of 36 (29.8%) patients (paroxysmal/persistent AF: 19 [24.7%]/17 [38.6%]) had AF recurrence in a mean 23 (range, 12-44) month follow-up period. The plasma hsCRP concentration in the recurrence group was significantly higher than that in the nonrecurrence group for all patients (median [quartile range] 2.22 [1.97] mg/L vs 0.89 [1.30] mg/L, P < 0.001), for patients with paroxysmal AF (2.12 [2.78] mg/L vs 0.84 [1.15] mg/L, P = 0.028), and for those with persistent AF (2.29 [1.08] mg/L vs 0.89 [1.53] mg/L, P = 0.005). Multiple logistic regression analyses showed that the higher level of the plasma hsCRP (P < 0.001) was a significant prognostic predictor of AF recurrence, both for patients with paroxysmal AF (P = 0.012) and those with persistent AF (P = 0.003). Plasma hsCRP concentration before CPVI was associated with AF recurrence after primary CPVI procedure for both paroxysmal and persistent AF patients. Plasma hsCRP concentration could play a role in prediction of AF recurrence after primary CPVI.

Effect of Central Obesity, Low High-Density Lipoprotein Cholesterol and C-Reactive Protein Polymorphisms on C-Reactive Protein Levels During Treatment With Rosuvastatin (10 mg Daily)

Plasma levels of high-sensitivity C-reactive protein (hsCRP) are an important predictor of cardiovascular disease, and achievement of lower targets of hsCRP with rosuvastatin treatment was associated with improved cardiovascular outcomes. The aim of this study was to examine whether hsCRP levels were related to genetic variants and traditional cardiovascular risk factors in Chinese patients treated with rosuvastatin 10 mg/day. The relations were analyzed between on-treatment plasma hsCRP concentrations and cardiovascular risk factors and 14 single-nucleotide polymorphisms in CRP and other candidate genes. In 281 patients with a median plasma hsCRP level of 0.81 mg/L (interquartile range 0.46 to 1.86), higher hsCRP levels were significantly associated with female gender, greater waist circumference (WC), having diabetes, higher triglycerides, and lower high-density lipoprotein (HDL) cholesterol. Three single-nucleotide polymorphisms (rs1205, 3872G>A and rs2808630, 5237A>G in CRP and rs1169288, I27L in HNF1A) were independently associated with hsCRP levels before and after adjustment for other variables. WC and the CRP rs1205 polymorphism showed the strongest relations with hsCRP, and in multiple regression analysis, gender, WC, diabetes, triglycerides, HDL cholesterol, and the 3 genetic variants explained 35.5% of the variance in hsCRP levels. The 2 CRP polymorphisms, female gender, higher WC, and lower HDL cholesterol were associated with risk for having CRP concentrations ≥ 1 mg/L. In conclusion, central obesity, low HDL cholesterol, and CRP polymorphisms are major determinants of higher hsCRP levels in Chinese patients receiving treatment with rosuvastatin.

Reproducibility in Serial C-Reactive Protein and Interleukin-6 Measurements in Post–Myocardial Infarction Patients: Results from the AIRGENE Study

Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) have received widespread interest, and a large database has been accumulated on their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among other things, by physiological variation, which is the natural within-individual variation occurring over time. Implementation of hsCRP and IL-6 measurement into clinical practice requires data on the reliability of such measurements. We serially measured hsCRP and IL-6 concentrations in up to 6 blood samples taken at monthly intervals from 200 post-myocardial infarction patients who participated in the AIRGENE study. The mean (SD) of the ln-transformed plasma concentrations (in milligrams per liter for hsCRP and nanograms per liter for IL-6) for all participants over all samples was 0.16 (1.04) for hsCRP and 0.76 (0.57) for IL-6, with no significant differences between men and women. The within-individual and analytical variance component for the ln-transformed hsCRP data was 0.37, and the between-individual variance component was 0.73. For the ln-transformed IL-6 data, these values were 0.11 and 0.22, respectively. A substantial part of the total variation in plasma hsCRP and IL-6 concentrations was explained by the between-individual variation (as a percentage of the total variance, 66.1% for the ln-transformed hsCRP data and 66.2% for the ln-transformed IL-6 data). For both markers, 2 measurements were needed to reach a sufficient reliability. Our results demonstrate considerable stability and good reproducibility for serial hsCRP and IL-6 measurements. Thus, there should be no major concern about misclassification in clinical practice if at least 2 subsequent measurements are taken.

Mild asthma in overweight women: A new phenotype?

Epidemics of asthma and overweight have been linked recently. They might be associated with systemic inflammation. In asthma hyperresponsiveness to adenosine (AMP) is more closely related to inflammation than to methacholine (MCh). The aim of the study was to determine responsiveness to AMP and MCh in overweight compared with normal weight asthmatics. Thirty women were enrolled (19 overweight) with mild controlled asthma according to GINA. A Body Mass Index (BMI) less than 25kg/m(2) was considered as normal and a BMI above 25kg/m(2) as overweight. We assessed the recent control of asthma (ACQ), pulmonary function tests, bronchial responsiveness to MCh and AMP (PC(20) and O'Connor two-point dose-response slope), perception of symptoms (Borg scale), and blood inflammatory markers (leptin and hs-CRP by ELISA). Overweight had a significant lower dose-response slope of the MCh challenge (p=0.009) as compared to normal weight patients, whereas no significant difference was observed for AMP challenge (p=0.27). Overweight patients had higher intercepts of the Borg scale measured before the MCh and AMP challenge tests (p=0.01 and p=0.03). Plasma leptin (p=0.001) and hs-CRP (p=0.05) concentrations were higher in overweight than normal weight patients. There was no correlation between challenges and inflammatory markers. Overweight asthmatic women have more pronounced systemic inflammation, but are less responsive to MCh. AMP responsiveness appeared to be comparable between both groups. Our findings suggest that overweight asthmatic women do not feature increased airway inflammation, but do represent a distinct phenotype as compared to normal weight patients.

Plasma adipokine and inflammatory marker concentrations are altered in obese, as opposed to non-obese, type 2 diabetes patients

Elevated plasma free fatty acid (FFA), inflammatory marker, and altered adipokine concentrations have been observed in obese type 2 diabetes patients. It remains unclear whether these altered plasma concentrations are related to the diabetic state or presence of obesity. In this cross-sectional observational study, we compare basal plasma FFA, inflammatory marker, and adipokine concentrations between obese and non-obese type 2 diabetes patients and healthy, non-obese controls. A total of 20 healthy, normoglycemic males (BMI <30 kg/m2), 20 non-obese (BMI <30 kg/m2) and 20 obese (BMI >35 kg/m2) type 2 diabetes patients were selected to participate in this study. Groups were matched for age and habitual physical activity level. Body composition, glycemic control, and exercise performance capacity were assessed. Basal blood samples were collected to determine plasma leptin, adiponectin, resistin, tumor necrosis factor α (TNFα), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and FFA concentrations. Plasma FFA, inflammatory marker (hsCRP, IL-6, TNFα), adipokine (adiponectin, resistin, leptin), and triglyceride concentrations did not differ between non-obese diabetes patients and healthy, normoglycemic controls. Plasma FFA, IL-6, hsCRP, leptin, and triglyceride levels were significantly higher in the obese diabetes patients when compared with the healthy normoglycemic controls (P < 0.05). Furthermore, plasma hsCRP and leptin levels were significantly higher in the obese versus non-obese diabetes patients (P < 0.05). Significant correlations between plasma parameters and glycemic control were observed, but disappeared after adjusting for trunk adipose tissue mass. Elevated plasma leptin, hsCRP, IL-6, and FFA concentrations are associated with obesity and not necessarily with the type 2 diabetic state.

Effect of rosuvastatin on concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma high-sensitivity C-reactive protein in hypercholesterolemic patients with and without type 2 diabetes mellitus: A 12-week, open-label, pilot study

Background: Oxidative stress and inflammation of the arterial wall are now recognized as important factors in the progression of atherosclerosis. C-reactive protein (CRP) has been defined as a sensitive but not specific marker of inflammation. Statin therapy has been reported to decrease plasma high-sensitivity CRP (hs-CRP) concentration in hypercholesterolemic patients. Objective: The aim of this study was to examine the effect of rosuvastatin on concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma hs-CRP in hypercholesterolemic patients with and without type 2 diabetes mellitus. Methods: Patients with hypercholesterolemia with and without type 2 diabetes mellitus were enrolled in this pilot study after written informed consent was given. At baseline and after 12 weeks of open-label treatment with rosuvastatin 2.5 mg/d, concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma hs-CRP were measured. Urine 8-iso-prostaglandin F 2α (8-iso-PGF 2α) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations were also measured to asess whole-body oxidative stress. Plasma free-radical generation was estimated using a total reactive oxygen species (TROS) assay system. Adverse effects were assessed at each study visit (4-week intervals) through patient interviews and laboratory testing. Results: Thirty-five patients were enrolled with 1 dropping out prior to study completion; therefore, 34 patients (19 women, 15 men; mean [SE] age, 55.4 [13.6] years; range, 30–78 years) completed the study. Compared with baseline, significant decreases were found in serum concentrations of total cholesterol (TC) (252.3 [39.3] vs 187.8 [30.1] mg/dL; P < 0.001; Δ = 24.5%), LDL-C (162.0 [44.3] vs 98.5 [31.9] mg/dL; P < 0.001; Δ = 38.7%), and triglycerides (TG) (157.2 [93.6] vs 124.4 [69.9] mg/dL; P < 0.05; Δ = 11.7%) after 12 weeks of treatment with rosuvastatin. Serum HDL-C concentration did not change significantly from baseline (59.7 [20.5] vs 63.7 [19.3] mg/dL; Δ = 9.4%). The plasma LDL-C/HDL-C ratio decreased significantly after rosuvastatin treatment (3.03 [1.33] vs 1.72 [0.83]; P < 0.001; Δ = 43.2%). Compared with baseline, significant decreases were observed in urine concentrations of the oxidative stress markers after 12 weeks of rosuvastatin treatment: 8-iso-PGF 2α (342.8 [154.3] vs 300.6 [101.2] pg/mg; P < 0.05) and 8-OHdG (11.1 [4.53] vs 8.1 [2.7] ng/mg; P < 0.01). TROS decreased significantly (182.3 [29.0] vs 157.6 [17.3] U; P < 0.001), and plasma hs-CRP concentration also decreased significantly (0.107 [0.100] vs 0.054 [0.033] mg/dL; P < 0.05). When the patients' results were assessed according to the presence or absence of type 2 diabetes mellitus, urine 8-iso-PGF 2α concentration was significantly decreased from baseline only in the nondiabetic group. No adverse events were reported or observed during the course of the study. Conclusion: Rosuvastatin treatment was associated with significant reductions in plasma concentrations of TC, LDL-C, and TG, urine and plasma oxidative stress markers, and plasma hs-CRP in these hypercholesterolemic patients.

Relationship between plasma inflammatory markers and plaque fibrous cap thickness determined by intravascular optical coherence tomography

ObjectiveThe purpose of this study was to evaluate the relationship between human plaque fibrous cap thickness detected by intravascular optical coherence tomography (OCT) and the plasma levels of inflammatory factors...

Plasma Procalcitonin Is an Independent Predictor of Graft Failure Late After Renal Transplantation

Chronic low-grade inflammation is involved in chronic transplant dysfunction after renal transplantation. Procalcitonin (PCT), known to reflect microbial inflammation, may also reflect ongoing noninfectious chronic low-grade inflammation in organ parenchyma, including transplanted kidneys. We aimed to compare predictive performance of plasma PCT for development of graft failure in renal transplant recipients (RTR) with that of high-sensitivity C-reactive protein (hsCRP), an established marker of systemic chronic low-grade inflammation. We included 575 RTR with functioning grafts for more than or equal to 1 year at a median (interquartile range) time of 6.1 (2.9-11.7) years posttransplant. PCT was determined using an ultrasensitive immunoluminometric assay and hsCRP using high-sensitivity enzyme-linked immunosorbent assay. Median (interquartile range) plasma PCT and hsCRP concentrations were 0.023 (0.017-0.036) ng/mL and 2.1 (0.8-4.9) mg/L, respectively. After a median (interquartile range) of 5.2 (4.5-5.7) years of follow-up, incidence of graft failure was 0.5%, 2.6%, and 18.5% according to increasing PCT tertiles (P<0.001 by log-rank test). Area under the curve of receiver operating characteristic analysis of PCT for prediction of graft failure was significantly higher than that of hsCRP (0.84 vs. 0.56, P<0.001). After adjustment for potential confounders, PCT remained an independent predictor of graft failure (hazard ratio=2.3 [95% confidence interval 1.4-3.7] per doubling PCT, P=0.0004), whereas this was not the case for hsCRP. We identified plasma PCT as a strong and an independent predictor of graft failure in RTR. These data suggest that PCT in RTR reflects ongoing inflammation in parenchyma of transplanted kidneys. Further studies are required to investigate whether PCT could be of use as an early biomarker for chronic transplant dysfunction.