Changes In hs-CRP Research Articles

Early changes in coagulation but not inflammatory biomarkers under intermittent ART: the randomized ANRS 106 WINDOW trial.

IntroductionIn the SMART trial, baseline plasma hsCRP, IL6 and D-dimer levels were strongly correlated to all-cause mortality. A case-control study has shown an increase of IL-6 and D-dimer levels after one month of antiretroviral therapy (ART) interruption, which was correlated to viral load. Restarting ART was associated to a decrease in D-dimer but not IL-6 or hsCRP levels. We assessed biomarkers levels up to 96 weeks in ART-experienced adults with plasma HIV RNA levels <400 c/mL randomized in the ANRS 106 WINDOW trial to intermittent ART (IT: six cycles of eight weeks of ART interruption followed by eight weeks of ART) versus continuous treatment (CT).MethodsStored plasma for 160 participants (80 IT and 80 CT), matched by age, sex and CDC classification, were analyzed blinded for IL-6, sCD-14, hsCRP and D-dimer levels at baseline, week 8 (IT group only), week 16 and week 96. Lower levels of detection for IL-6, sCD14, hsCRP and D-Dimer were 1.5 pg/mL, 250 ng/mL, 0.03 µg/mL and 0.21 µg/mL, respectively. The primary objective was to compare changes in IL-6, hsCRP, sCD14 and D-dimer plasma levels from baseline to week 8, 16 and 96 in the IT and CT arms. Biomarkers levels were log10 transformed prior to analysis.ResultsAt baseline, patients were mostly men (86%), with a median age of 40 years, a CD4+ T-cell count of 768/mm3, have received a median of 4.7 years of ART and 85% had HIV RNA <50 c/mL. Proportion of patients with plasma HIV RNA levels<400 c/mL were 6% and 99%, 81% and 97%, 86% and 92% at weeks 8, 16 and 96 in the IT and CT arms, respectively. Plasma biomarkers levels are shown in the Table 1.Compared to baseline, D-dimer levels significantly increased 8 weeks after ART interruption in the IT arm (+23% fold change, 95% CI +9% to +39%) but reverted to baseline levels at week 16 and remained unchanged at week 96. There was no significant change from baseline in the other biomarker levels in the IT arm. Similarly, no significant change from baseline in biomarker levels was seen in the CT arm up to 96 weeks.ConclusionCoagulation and inflammatory biomarkers levels remained stable over 96 weeks in well-suppressed HIV-infected patient on ART. Following ART interruption there was a significant increase in D-dimer but not in inflammatory biomarkers levels. This increase was reversed upon reintroduction of ART. These data suggest that ART interruption increases coagulation rather than inflammatory biomarkers.

Shift rotation and age – interactions with sleep–wakefulness and inflammation

The interaction of age with shift rotation in relation to sleep–wakefulness and inflammation were studied among male employees (n = 772). Cross-sectional analyses in day, two-shift and three-shift work with different shift rotations, as well as changes in leukocytes and hsCRP among three shift workers who changed their shift system during the 2.5- yr follow-up were completed. Shift work was associated with problems to fall asleep (p < 0.001) and feeling of the current working time being harmful to sleep and wakefulness (p < 0.001). Quickly forward-rotation shift workers considered their working time less harmful compared with slower backward-rotation shift workers. Age did not influence sleep in general, but older workers in the quickly forward-rotating three-shift system had less sleep complaints than their younger colleagues. The age differences in the inflammatory markers partly depended on the shift system. The results give some support that rapidly forward-rotating shift systems are more ‘age-friendly’ than backward-rotating shift systems.

Pharmacokinetic and Pharmacodynamic Characteristics of Single-dose Canakinumab in Patients With Type 2 Diabetes Mellitus

PurposeInterleukin (IL)-1β, an inflammatory molecule, contributes to the development of atherothrombosis and worsening of islet β-cell function. Canakinumab, a human monoclonal antibody, targets IL-1β–dependent inflammation and reduces the vascular inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), and other inflammatory cardiovascular biomarkers. Here, we aimed to assess the pharmacokinetic (PK) and pharmacodynamic characteristics, including the effect on hsCRP, of canakinumab in patients with type 2 diabetes mellitus (T2DM) after a 2-hour single-dose intravenous infusion. MethodsThis multicenter, randomized, double-blind, placebo-controlled, dose-escalation study was conducted in patients with T2DM (diagnosed ≥6 months before screening) on a stable daily dose of metformin. Patients were randomly assigned to receive a single intravenous dose of canakinumab 0.03, 0.1, 0.3, 1.5, or 10 mg/kg or placebo. The study was initially designed with 1 small cohort (15 patients, 0.3 mg/kg) on a stable dose of metformin ≥500 mg/d for an initial tolerability evaluation; all other patients were on a stable dose of ≥850 mg/d of metformin. The PK profile was assessed at 0 and 2 hours and at days 2, 14, 28, 56, 84, and 168. Changes in hsCRP and hemoglobin (Hb) A1c levels were assessed at weeks 4, 8, 12, and 24. FindingsOf the 231 enrolled patients, 222 completed the study. Median hsCRP values at screening ranged from 1.8 to 3.2 mg/L, and the median daily dose of metformin ranged from 1000 to 2000 mg. Exposure to canakinumab was dose proportional. The mean half-life ranged from 17 to 26 days, and mean systemic clearance ranged from 0.094 to 0.128 mL/h/kg. Dose-related reductions in hsCRP were significantly greater with canakinumab compared with those with placebo at week 4 (−0.2 mg/L, −0.5 mg/L, −1.5 mg/L, and −1.7 mg/L with the 0.1-, 0.3-, 1.5-, and 10-mg/kg doses, respectively; all, P < 0.05). Significant reductions in hsCRP were maintained up to week 12 with the 2 highest doses of canakinumab (−0.8 mg/L with 1.5 mg/kg and −1.3 mg/L with 10 mg/kg; both, P < 0.05). A placebo-adjusted decrease in HbA1c of 0.31% at week 12 was reported with canakinumab 10 mg/kg (P = 0.038), and a reduction of 0.23% at week 4 was found with canakinumab 1.5 mg/kg (P = 0.011). ImplicationsThe findings from this study suggest that IL-1β blockade after single-dose administration of canakinumab at 1.5 and 10 mg/kg provided sustained suppression of hsCRP levels for 12 weeks in patients with T2DM. ClinicalTrials.gov identifier: NCT00900146.

The influence of vitamin D analogs on calcification modulators, N-terminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients: a randomized crossover study.

BackgroundThe risk of cardiovascular disease is tremendously high in dialysis patients. Dialysis patients treated with vitamin D analogs show decreased cardiovascular morbidity and mortality compared with untreated patients. We examined the influence of two common vitamin D analogs, alfacalcidol and paricalcitol, on important cardiovascular biomarkers in hemodialysis patients. Anti-inflammatory effects and the influence on regulators of vascular calcification as well as markers of heart failure were examined.MethodsIn 57 chronic hemodialysis patients enrolled in a randomized crossover trial comparing paricalcitol and alfacalcidol, we examined the changes in osteoprotegerin, fetuin-A, NT-proBNP, hs-Crp, IL-6 and TNF-α, during 16 weeks of treatment.ResultsNT-proBNP and osteoprotegerin increased comparably in the paricalcitol and alfacalcidol-treated groups. Fetuin-A increased significantly in the alfacalcidol-treated group compared with the paricalcitol-treated group (difference 32.84 μmol/l (95% C.I.; range 0.21–67.47)) during the first treatment period. No difference was found between the groups during the second treatment period, and IL-6, TNF-α and hs-Crp were unchanged in both treatment groups.ConclusionsParicalcitol and alfacalcidol modulate regulators of vascular calcification. Alfacalcidol may increase the level of the calcification inhibitor fetuin-A. We did not find any anti-inflammatory effect or difference in changes of NT-proBNP.Trial registryClinicalTrials.gov NCT00469599 May 3 2007.

Beneficial effects of adaptive servo-ventilation therapy on albuminuria in patients with heart failure

BackgroundShort-duration adaptive servo-ventilation (ASV) therapy can be effective for heart failure (HF) patients. Albuminuria is recognized as a prognostic marker for HF. We investigated whether short-duration and short-term ASV therapy reduced albuminuria in HF patients. Methods and resultsTwenty-one consecutive HF patients were divided into two groups: those who tolerated ASV therapy (ASV group, n=14) and those who did not (non-ASV group, n=7). ASV therapy was administered to enrolled patients for 1 week for 2h per day (1h in the morning and 1h in the afternoon). The urinary albumin to creatinine ratio (UACR), urinary 24h norepinephrine (NE) excretion, high-sensitivity C-reactive protein (hs-CRP), and plasma brain natriuretic peptide (BNP) levels were measured before and 1 week after ASV therapy. In the ASV group, but not the non-ASV group, the UACR significantly decreased, together with a decrease in urinary NE and hs-CRP levels. There were significant correlations between the changes in UACR and hs-CRP and between the changes in urinary NE and hs-CRP. Multiple linear regression analyses indicated that ASV use was the strongest predictor of decreased UACR. ConclusionAlbuminuria, urinary NE, and hs-CRP levels reduced in HF patients who could receive short-duration and short-term ASV therapy. Anti-inflammatory effects of ASV therapy may partly mediate the reduction of albuminuria.

Overall sleep status and high sensitivity C-reactive protein: a prospective study in Japanese factory workers.

We investigated the relation between overall sleep status based on the modified Pittsburgh Sleep Quality Index (PSQI) global score and subsequent changes in serum high-sensitivity C-reactive protein (hsCRP) in a population of Japanese factory workers, who were predominantly female. A total of 991 Japanese with inflammation classified as low cardiovascular risk (baseline hsCRP<1.0mgL(-1) ) were grouped according to the presence or absence of unfavourable sleep, defined as a modified PSQI global score>5.5 points. The subsequent changes in hsCRP after 3years were then compared in the two groups. Analysis of covariance incorporating log-transformed baseline hsCRP, age, sex, lifestyle and physical and biochemical profiles was used to compare the geometric means of hsCRP at year 3 in each sleep status group. A logistic regression model incorporating the same variables was used to calculate the odds ratios for development of inflammation with a medium-to-high cardiovascular risk (hsCRP at year 3≥1.0mgL(-1) ) comparing the presence or absence of unfavourable sleep habits. The multivariate-adjusted geometric mean of hsCRP at year 3 was significantly higher in subjects with unfavourable sleep habits compared with those with a normal pattern (0.275 versus 0.242mgL(-1) ). The multivariate-adjusted odds ratio for developing increased and potentially pathogenic levels of inflammation due to unfavourable sleep was 2.08 (95% confidence interval=1.29-3.35). There was a significant linear trend for the development of increased inflammation across the modified PSQI global scores (P=0.04). Unfavourable sleep is associated with activation of low-grade systemic inflammation.

Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial.

The aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases, insulin resistance, oxidative stress, and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease (NAFLD). Fifty-three patients with NAFLD were enrolled in a parallel, double-blind, placebo-controlled study. The patients were randomly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 (n = 27) or a placebo (n = 26), every 14 days for 4 months. Serum aminotransferases, high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor α, malondialdehyde (MDA), total antioxidant capacity, transforming growth factor β1, as well as grade of hepatic steatosis and homeostasis model assessment of insulin resistance were assessed pre- and post-intervention. In patients who received vitamin D supplement compared to the controls, the median of serum 25(OH)D3 significantly increased (16.2 vs. 1.6 ng/ml, P < 0.001). This increase accompanied by significant decrease in serum MDA (-2.09 vs. -1.23 ng/ml, P = 0.03) and near significant changes in serum hs-CRP (-0.25 vs. 0.22 mg/l, P = 0.06). These between-group differences remained significant even after controlling for baseline covariates. Other variables showed no significant changes. Improved vitamin D status led to amelioration in serum hs-CRP and MDA in patients with NAFLD. This might be considered as an adjunctive therapy to attenuate systemic inflammation and lipid peroxidation alongside other treatments for NAFLD patients.

Alterations of plant sterols, lathosterol, oxidative stress and inflammatory markers after the combination therapy of ezetimibe and statin drugs in type 2 diabetic patients

The elevation of serum plant sterols in addition to serum LDL-cholesterol (LDL-C) is one of the important risk factors for coronary heart disease. We investigated how to alterations of serum hepatic synthesised cholesterol and plant sterols levels, clinical markers for inflammation and oxidative stress after combination therapy with ezetimibe, an inhibitor of cholesterol transporter in the small intestinal colon, and statin drugs in type 2 diabetic patients. Studies were conducted in 28 patients with type 2 diabetes mellitus complicated with dyslipidemia. Patients were divided into 3 groups as follows: the 1st group is 7 patients treated with 10mg ezetimibe sequent on pretreatment with mild statin drug (MS+E group), and the 2nd group is 7 patients treated with 10mg ezetimibe sequent on pretreatment with strong statin drug (SS+E group), and then the 3rd group is 14 patients treated with 10mg ezetimibe alone without pretreatment with any statin drugs (naïve E group). In addition to various metabolic markers, serum plant sterols such as sitosterol and campesterol, and hepatic synthesised cholesterol such as lathosterol were measured by the gas liquid chromatography. Serum highly sensitive CRP (hsCRP) as an inflammation marker, and then malonyldealdehyde (MDA) and carbonyl-modified protein (CMP) as an oxidative stress were assayed by the conventional method, respectively. Fasting plasma glucose and serum glucosylated HbA1c (JDS value) did not show any significant changes after administration of ezetimibe in whole groups. Serum LDL-C was reduced significantly and serum triglyceride exhibited a tendency of reduction in whole groups. Serum sitosterol and campesterol were decreased significantly, while serum lathosterol was increased significantly or markedly in whole patients and also in each group. There were no significant changes in serum hsCRP in whole groups. Both serum MDA and CMP revealed significant or marked reductions in each group. The present investigation suggests that the combination therapy of the ezetimibe and statin drugs is potential to remarkably reduce serum LDL-C, plant sterols, MDA and CMP, and therefore might lead to prevent atherosclerosis.

The effect of L-thyroxine substitution on lipid profile, glucose homeostasis, inflammation and coagulation in patients with subclinical hypothyroidism

Subclinical hypothyroidism (SH) is associated with increased risk for atherosclerosis, mainly attributable to dyslipidaemia and hypercoagulability. However, conflicting data exist regarding the effect of L-thyroxine substitution on these parameters. The purpose of this study was to assess the effect of L-thyroxine therapy on lipidaemic profile, coagulation markers, high-sensitivity C-reactive protein (hsCRP) and glucose homoeostasis in SH patients. It was a prospective open-label study. The following parameters were measured before and 6 months after intervention: anthropometric data, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins B (apoB) and A1 (apoA1), lipoprotein (a) [Lp(a)], fasting plasma glucose and insulin, homoeostasis model assessment-insulin resistance (HOMA-IR), hsCRP, antithrombin III (AT-III), protein C (PC), protein S (PS), fibrinogen and homocysteine. Thirty-two patients (30 women) aged 52.1 ± 13.9 years with SH completed the study. Baseline mean TSH levels were 6.79 ± 2.58 mIU/ml. Achievement of euthyroidism significantly reduced systolic blood pressure (BP) in patients with SH (from 135.2 ± 18.5 to 129.7 ± 15.8 mmHg, p = 0.03) and diastolic BP only in those with baseline TSH levels > 7 mIU/ml (from 79.5 ± 9.8 to 72.1 ± 7.3 mmHg, p = 0.03). No significant changes in body weight, TC, LDL-C, HDL-C, TG, apoB, glucose, insulin, HOMA-IR, hsCRP, AT-III, PC, PS, fibrinogen or homocysteine levels were noticed after restoration of euthyroidism, except for a decrease in apoA1 (p = 0.04) and an increase in Lp(a) levels (p = 0.02). Except for a reduction in systolic and diastolic BP, thyroid substitution therapy does not affect lipidaemic profile, systematic inflammation, glucose homoeostasis or coagulation in patients with SH.

Statins combined with exercise are associated with the increased renal function mediated by high-molecular-weight adiponectin in coronary artery disease patients

BackgroundStatins and exercise therapy are clinically effective in preventing cardiovascular events in patients with coronary artery disease (CAD). The aim of this study was to determine the effects of statins combined with exercise on the renal function of CAD patients. MethodsWe performed a sub-analysis of a clinical trial that determined the 20-week-effects of two statins (rosuvastatin, n=14; atorvastatin, n=14) combined with regular exercise on renal function, as assessed by the estimated glomerular filtration rates (eGFRs) of CAD patients. ResultsThe combination of statins and exercise therapy increased eGFRs from 61.1±16.6 at baseline to 65.8±16.8ml/min/per 1.73m2 (p=0.03), increased serum levels of high-molecular-weight (HMW) adiponectin, increased ubiquinol/low-density lipoprotein cholesterol (LDL-C) ratios, and decreased high sensitivity C-reactive protein (hs-CRP). Changes in HMW-adiponectin, ubiquinol/LDL-C ratios and hs-CRP were significantly correlated with changes in eGFR (r=0.597, p=0.001; r=0.437, p=0.02; and r=−0.473, p=0.01, respectively). Treatment-induced increases in HMW-adiponectin independently correlated with the increases in eGFR (β=0.513, p=0.02) in a multivariate analysis. Both atorvastatin and rosuvastatin combined with regular exercise produced increases in eGFR. The patients treated with rosuvastatin exhibited significant improvements in eGFR. ConclusionStatins combined with exercise significantly increased eGFR in CAD patients, and these improvements in renal function were correlated with increases in HMW-adiponectin levels. The statins–exercise combination treatment may have provided clinical benefits for patients with CAD partly through the improvement in renal function.

Change in growth differentiation factor 15, but not C-reactive protein, independently predicts major cardiac events in patients with non-ST elevation acute coronary syndrome.

Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and growth-differentiation factor-15 (GDF-15) have received widespread interest, with their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among others, by physiological variations, which are the natural, within-individual variation occurring over time. The aims of our study are: (a) to describe the changes in hsCRP and GDF-15 levels over a period of time and after an episode of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and (b) to examine whether the rate of change in hsCRP and GDF-15 after the acute event is associated with long-term major cardiovascular adverse events (MACE). Two hundred and Fifty five NSTE-ACS patients were included in the study. We measured hsCRP and GDF-15 concentrations, at admission and again 36 months after admission (end of the follow-up period). The present study shows that the change of hsCRP levels, measured after 36 months, does not predict MACE in NSTEACS-patients. However, the level of GDF-15 measured, after 36 months, was a stronger predictor of MACE, in comparison to the acute unstable phase.

Cutaneous microvascular adaptation to repeated passive core heating in humans

Background: The high sensitivity C Reactive Protein (hsCRP) which was once considered a risk marker associated with cardiovascular diseases is increasingly considered as an independent risk factor which has atherogenic potential. Objectives: To determine whether a dose response relationship exists between exercise intensity and hsCRP in sedentary individuals. Methods/design: A four year randomized, active controlled, parallel group, outcome assessor blind, multiple arm trial. Procedure: 98 sedentary (otherwise healthy) individuals with a baseline hsCRP of more than 1mg/L and less than 15mg/L were randomly allocated to one of the four groups (Control, and three exercise groupswith escalating intensities of exercise). Three exercise groups were administered an exercise program at 50–60%, 60–70% and 70–80% based on heart rate reserve method, respectively for eight weeks. Concentration of hsCRP was measured at baseline andafter eightweeksusing immunoturbidimetry. The secondary outcome measures in this trial were peak oxygen uptake, waist circumference, fat percentage and body mass index. Results: Participants had amean (range) age of 23.3 (18–36) and a mean (range) body mass index of 26.6 (17.1–36.8). The hsCRP data was rank transformed as it did not follow normal distribution. The results indicated that there was no dose response relationship between exercise intensity and reduction in hsCRP (F=1.603, p=0.19). After removing six participants who had an increase in hsCRPofmore than30% frombaseline after eightweeks,we found a significant reduction of 38% in participantswhowere in the 60–70% intensity and about 25% in participants with 50–60 and 70–80% intensity (F=3.63, p<0.05). The changes in hsCRP among exercise groupswere independent of the changes observed in the secondary outcome measures. Conclusion: There is no convincing evidence for a dose response relationship between exercise intensity and hsCRP, however short term aerobic training (eight weeks) at 60–70% intensity has a role in reducing subclinical inflammation. The threshold intensity for exercise to have a beneficial effect on the inflammatory front appears to be 60% based on heart rate reserve method.

Abstract 18369: Interleukin-1 Blockade Improves Exercise Capacity in Heart Failure With Preserved Ejection Fraction (HFpEF): Results of the D-HART Study

Treatment options remain limited for patients with heart failure and preserved ejection fraction (HFpEF). Reduced exercise capacity is a common finding in HFpEF. Peak oxygen consumption (peak VO2) represents a gold standard for functional capacity and is a strong independent predictor of adverse outcomes. HFpEF patients also exhibit high levels of systemic inflammation that may be associated with mechanisms of diastolic dysfunction. We enrolled 12 patients with symptomatic HFpEF (LVEF&gt;50% and evidence of abnormal LV relaxation, filling, diastolic distensibility, or diastolic stiffness) and elevated hsCRP (&gt;2 mg/L). Patients were randomized to 14 day crossover treatment with daily subcutaneous injections of IL-1 receptor antagonist (anakinra); 100 mg or matching placebo in a double blind fashion ( NCT01542502 ). The pre-specified primary endpoint was change in peak VO2. Cardiopulmonary exercise testing was performed at baseline and upon completion of each treatment course. We observed a significant improvement in peak VO2 (+1.1 vs -0.1 ml•kg-1•min-1, P=0.009) and the oxygen uptake efficiency slope (+0.23 vs +0.09, P=0.006) and a significant reduction in hsCRP (-84% vs -10%, P=0.006) upon completion of anakinra treatment versus placebo. Correlative studies also revealed significant associations between changes in peak VO2 and hsCRP (R=-0.60, P=0.002). Improvements in ventilator efficiency (VE/VCO2 slope) were limited to patients with above median values for ventilator efficiency (VE/VCO2 slope&gt;26), suggesting that maximum benefits may occur in patients with impaired baseline function. These findings support the hypothesis that systemic inflammation and exercise intolerance in HFpEF are, at least in part, IL-1-dependent and provide the rationale for larger randomized clinical trials to confirm the benefits of IL-1 blockade in patients with HFpEF.

Study on the relationship of the syndrome of patients with type 2 diabetes and hs-CRP,IL-6 and insulin secretion index

Objective To compare the changes of hs-CRP,IL-6 level,insulin secretion index (HOMA-β),insulin resistance index (HOMA-IR) in the different TCM Hou of type 2 diabetic patients.Methods 63 newly diagnosed type 2 diabetic patients were selected.According to the TCM syndrome,they were divided into combination of phlegm and heat,deficiency of both qi and yin,yin and yang deficiency three groups.20 healthy people were selected as control group.The serum hs-CRP,IL-6 and fasting blood glucose,insulin were measured.Results The levels of hs-CRP,IL-6 and insulin resistance index were lower than the other three groups,there were significant differences (t =6.948,P ＜ 0.05).There was no significant difference in insulin secretion index between the control group and the combination of phlegm and heat gruop (t =4.832,P ＞ 0.05).There were significant differences in IL-6 level and HOMA-β among different syndromes groups(t =4.985,5.043,P ＜0.05).HOMA-β from high to low was the combination of phlegm and heat group ＞ deficiency of both qi and yin group ＞ yin and yang deficiency group.Conclusion The change of IL-6 correlates with TCM syndromes,and the change of TCM syndrome with the change of islet function.IL-6 and insulin secretion index can be used as reference of TCM type. Key words: Type 2 diabetes ; Inflammatory factors; Insulin secretion index; Dialectical typing

Effect of Rosuvastatin on OX40L and PPAR-γ Expression in Human Umbilical Vein Endothelial Cells and Atherosclerotic Cerebral Infarction Patients

Atherosclerotic cerebral infarction (ACI) is characterized by extremely high fatality and disability rate. Recent studies indicate that co-stimulatory signal of tumor necrosis factor superfamily OX40/OX40L contributes to the atherosclerosis effect in ACI patients. However, it remains unclear the mechanism underlying the anti-atherosclerosis process. So this study aims to investigate the effects of rosuvastatin on the expression of OX40L, peroxisome proliferator-activated receptors gamma (PPAR-γ) in human umbilical vein endothelial cells (HUVEC), and human peripheral blood lymphocytes. Different concentration of rosuvastatin and oxidized low-density lipoprotein (OX-LDL) co-intervene HUVEC to observe the expression of OX40L and PPAR-γ using real-time quantitative RT-PCR (Q-RTPCR) and Western-blot. Furthermore, we examined the level changes of plasmic sOX40L and hs-CRP in acute atherosclerotic cerebral infarction patients. The results demonstrated that concentration-dependent and time-dependent OX-LDL remarkably stimulate the expression of OX40L and inhibit the expression of PPAR-γ in vitro. But concentration-dependent rosuvastatin can reverse the impact of OX-LDL, suggesting that rosuvastatin can prevent the expression of OX40L, and the process may be associated with mevalonate pathway. In vivo, acute atherosclerotic cerebral infarction patients taking 20 mg rosuvastatin exhibited significantly reduced expression of OX40L in peripheral blood lymphocyte, sOX40L in blood plasma, and hs-CRP compared with before treatment. Our studies identified rosuvastatin as an effective medicine in controlling atherosclerosis process in ACI by inhibiting OX40L and stimulating PPAR-γ expression.

Metformin Increases the Novel Adipokine Cartonectin/CTRP3 in Women With Polycystic Ovary Syndrome

Recently cartonectin was reported as a novel adipokine, with lower levels in diet-induced obese mice, glucose-lowering effects, and antiinflammatory and cardioprotective properties. Polycystic ovary syndrome (PCOS) is a proinflammatory state associated with obesity, diabetes, dyslipidemia, and cardiovascular complications. The objective of the study was to investigate cartonectin levels and regulation in sera and adipose tissue (AT) as well as the effects of metformin of women with PCOS and control subjects. This was a cross-sectional study [PCOS (n = 83) and control (n = 39) subjects]. Real-time PCR and Western blotting were used to assess mRNA and protein expression of cartonectin. Serum cartonectin was measured by an ELISA. Serum and omental adipose tissue cartonectin were significantly lower in women with PCOS compared with control subjects (P < .05 and P < .01, respectively). Furthermore, cartonectin showed a significant negative association with body mass index, waist to hip ratio, glucose, insulin, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, High sensitivity C-reactive protein (hs-CRP) and intima-media thickness (P < .05 and P < .01, respectively); in multiple regression analyses, triglycerides (P =.040) and hs-CRP (P = .031) were predictive of cartonectin levels (P < .05). After 6 months of metformin treatment, there was an associated increase in serum cartonectin (P < .05). Importantly, changes in hs-CRP were significantly negatively correlated with changes in serum cartonectin (P = .033). Finally, cartonectin protein production and secretion into conditioned media were significantly increased by metformin in control human omental AT explants (P < .05). Serum and omental AT cartonectin are lower in women with PCOS. Metformin treatment increases serum cartonectin levels in these women and in omental AT explants.

A population-based dietary inflammatory index predicts levels of C-reactive protein in the Seasonal Variation of Blood Cholesterol Study (SEASONS)

To perform construct validation of the population-based Dietary Inflammatory Index (DII) using dietary data from two different dietary assessments and serum high-sensitivity C-reactive protein (hs-CRP) as the construct validator. Using data derived from (i) three 24 h dietary recalls (24HR) at baseline and at the end of each subsequent quarter (i.e. up to fifteen over a year) and (ii) a 7 d dietary recall (7DDR) measured at baseline and then quarterly, regression analyses were conducted to test the effect of the DII score on serum hs-CRP as dichotomous (≤3 mg/l, >3 mg/l), while controlling for important potential confounders. Existing data from the Seasonal Variation of Blood Cholesterol Study (SEASONS), a longitudinal observational study of healthy participants recruited in Worcester, MA, USA and participants were followed for 1 year. Participants who had at least one hs-CRP measurement over her/his 1-year participation (n 495 for 24HR, n 559 for 7DDR). Higher DII scores were associated with values of hs-CRP >3 mg/l (OR = 1·08; 95 % CI 1·01, 1·16, P = 0·035 for the 24HR; and OR = 1·10; 95 % CI 1·02, 1·19, P = 0·015 for the 7DDR). The population-based DII was associated with interval changes in hs-CRP using both the 24HR and 7DDR. The success of this first-of-a-kind attempt at relating individuals' intakes of inflammation-modulating foods using this refined DII, and the finding that there is virtually no drop-off in predictive capability using a structured questionnaire in comparison to the 24HR standard, sets the stage for use of the DII in a wide variety of other epidemiological and clinical studies.

Effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus: Subgroup analysis of a double-blind randomized controlled trial

The purpose of this study was to identify the effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus (SLE). Subgroup data were analyzed for postmenopausal female SLE patients who participated in a randomized controlled trial of raloxifene on glucocorticoid-induced osteoporosis. Patients who were receiving a stable daily dose of prednisolone (≤10 mg) for ≥6 months were assigned to receive raloxifene (60 mg/day) or placebo on top of calcium and vitamin D. Disease activity was assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA), SLE disease activity index (SLEDAI) and physicians' global assessment (PGA) every three months. Lupus flares were assessed by the SELENA flare instrument. Serial serum levels of homocysteine, high-sensitivity C-reactive protein (hsCRP) and soluble thrombomodulin (sTM) were measured. A total of 62 patients (30 raloxifene, 32 placebo) were studied (age 52.5 ± 6.7 years; SLE duration 9.3 ± 7.6 years; menopause duration 7.2 ± 6.6 years). The SLEDAI at entry was 1.8 ± 2.3 (SLEDAI ≥ 6 in 8%). After 12 months, a significant gain in bone mineral density (BMD) of the lumbar spine (1.6%, p = 0.02), and reduction in bone resorption and formation markers was observed in the raloxifene but not in the placebo treated patients. The SELENA-SLEDAI and PGA scores area under the curve over 12 months were not significantly different between the two groups. There were three episodes of mild/moderate lupus flares (33% musculoskeletal, 33% dermatological) in the raloxifene group, compared to nine episodes of mild/moderate flares (27% musculoskeletal, 45% dermatological) in the placebo group (p = 0.11). The low density lipoprotein (LDL) cholesterol level increased significantly in the placebo but not raloxifene treated patients. No significant changes in homocysteine, hsCRP and sTM levels were observed in either group of patients. Raloxifene significantly improves lumbar spine BMD in SLE patients but does not cause an increase in lupus activity or flares.

Circulating Markers of Endothelial Dysfunction and Platelet Activation in Patients with Severe Symptomatic Cerebral Small Vessel Disease

Background: Small deep infarcts (SDI), also called lacunar infarcts, resulting from the occlusion of deep branch arteries, account for 25% of ischemic strokes. The physiopathology of the disease remains largely unknown. However, evidence about the role of endothelial dysfunction has emerged. Whereas chronic platelet activation is of major importance in acute thrombosis of large atherosclerotic arteries, its role in SDI remains unclear. Frequently associated risk factors are hypertension and diabetes mellitus. The aim of this study was to determine platelet and endothelial activation in patients with recent SDI in comparison to population-based control subjects matched for age, sex and vascular risk factors. Methods: Platelet activation markers (activated glycoprotein IIb/IIIa, P-selectin and platelet microparticles), shear-induced platelet aggregation (SIPA) studied in the SIPAgreg device at 4,000 s^-1, endothelial activation markers [including von Willebrand factor (vWF) antigen and homocysteine] and high-sensitivity C-reactive protein (hsCRP) were measured in 74 consecutive patients with recent SDI, in whom detectable large artery atherosclerosis or cardiac embolism had been ruled out. Blood samples were collected 1 and 3 months after symptom onset. These factors were also measured in 74 population-based controls with no stroke history and matched for age, sex, hypertension and diabetes. Results: One month after symptom onset, the patients had similar levels of platelet activation to matched controls (p > 0.40 for all comparisons). In contrast, endothelial activation parameters were increased in patients in comparison to controls (vWF: p = 0.002 and homocysteinemia/creatinemia: p = 0.025). The level of hsCRP was slightly increased in patients compared to controls (p = 0.059). At 3 months, we observed a significant decrease in vWF and hsCRP levels in patients (median change in vWF = 10%, p = 0.004; median change in hsCRP = 0.4 mg/l, p = 0.02). Homocysteine levels and all platelet parameters remained unchanged at this time compared to at 1 month. Conclusions: Our results confirm that chronic platelet activation, when compared to controls matched for age, sex and vascular risk factors, did not seem to play a central role in the pathophysiology of lacunar stroke. In contrast, we found markers of endothelial dysfunction, the role of which in the occurrence of lacunar infarction has still to be clarified in further studies.

Increasing high-sensitive C-reactive protein level predicts peritonitis risk in chronic peritoneal dialysis patients

BackgroundThe aim of this study was to evaluate whether a high baseline level of high-sensitivity C-reactive protein (hs-CRP) or changes in the level predicts the risk of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD).MethodsA prospective, cross-sectional, case–control study was conducted in a single hospital-based PD unit. A total of 327 patients were included in the study. Serum hs-CRP was measured annually for 2 years. Patients were divided into 4 groups according to the changes in annual hs-CRP levels (at baseline and at 1 year intervals): group 1 (from <5 mg/L to <5 mg/L, n = 171), group 2 (from <5 mg/L to ≥5 mg/L, n = 45), group 3 (from ≥5 mg/L to <5 mg/L, n = 45), and group 4 (from ≥5 mg/L to ≥5 mg/L, n = 80). Demographics, biochemistry results, PD adequacy indices, and peritonitis risk were compared between the groups.ResultsThe initial serum albumin level was similar in the 4 groups (p = 0.12). There was a negative linear correlation between the serial albumin change (∆alb) and serial hs-CRP change (∆hs-CRP; r = −0.154, p = 0.005). The hazard ratio (HR) for peritonitis was significantly higher in group 2 (HR = 1, reference) than in group 4 (HR = 0.401, 95% CI 0.209 − 0.769). Group 2 had a greater serum albumin decline rate (∆alb: –3% ± 9%) and hs-CRP elevation rate (∆hs-CRP: 835% ± 1232%) compared to those for the other groups.ConclusionsA progressive increase in the hs-CRP level was associated with a corresponding decline in the serum albumin level. Progressive rather than persistently high levels of serum hs-CRP predicted peritonitis risk in CAPD patients.