Significant Reduction In hsCRP Research Articles

Exploratory secondary analyses of a cognitive-behavioral intervention for knee osteoarthritis demonstrate reduction in biomarkers of adipocyte inflammation

To investigate the effects of pain coping skills training (PCST) and a lifestyle behavioral weight management (BWM) program on inflammatory markers and biomarker associations with pain and function in the OA LIFE study. Serum samples were available from a subset (N=169) of the overweight or obese knee OA participants in the OA LIFE study that evaluated: PCST, BWM, combined PCST+BWM, or standard care (SC). Inflammatory markers (hsCRP, IL-1ra, IL-1β, IL-6, IL-8, TNF-α, TNFRI, TNFRII, and hyaluronic acid (HA)), and adipokines (leptin and adiponectin) were measured before and after the 24-week treatment period. Biomarkers were assessed for effects of treatment and for associations with change in weight, pain and disability (unadjusted and adjusted for age, race, sex, baseline body mass index (BMI), and baseline biomarker concentration). PCST+BWM was associated with significant reductions in hsCRP (P=0.0014), IL-6 (P=0.0075), and leptin (P=0.0001). After adjustment, there was a significant effect of PCST+BWM on changes in leptin (b=-0.19, P=0.01) and IL-6 (b=-0.25, P=0.02) relative to SC. Reductions in leptin and IL-6 were significantly correlated with reductions in weight, BMI and Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain; reductions in IL-6 were correlated with improvements in WOMAC and Arthritis Impact Measurement Scales (AIMS) physical function. By mediation analyses, weight loss was responsible for 54% of the change in IL-6 and all of the change in leptin. OA-related inflammatory markers were reduced by a 24-week combined PCST+BWM intervention. This suggests that the inflammatory state can be successfully modified in the context of a readily instituted clinical intervention with a positive clinical outcome.

Total Convection Affects Serum β2 Microglobulin and C-Reactive Protein but Not Erythropoietin Requirement following Post-Dilutional Hemodiafiltration

Background: Inflammation and increased erythropoiesis stimulating agents (ESA) requirement are frequently associated in patients on dialysis. On-line hemodiafiltration (ol-HDF), putting together high levels of diffusion, and convection could improve both conditions. However, it is still not known which depurative component plays a major role in determining this result. The aim of the study was to evaluate the role of convection and diffusion on long-term variations of serum β₂ microglobulin (Δβ₂M), high-sensitive C-reactive protein (ΔhsCRP) concentrations, and ESA requirement (ΔESA) in ol-HDF. Methods: Seventy-three patients prevalent on high flux HD (hfHD) were studied. Thirty-eight patients were switched from hfHD to post-dilutional ol-HDF (Study group); the other 35 patients were considered the Control group. At 6 and 12 months, the effects of ol-HDF and hfHD on ΔhsCRP, ΔB₂M, and ΔESA (U/kg/week) were evaluated. Other variables considered were body weight (BW), serum albumin (sAlb), hemoglobin (Hb), and equilibrated Kt/V (eKt/V). Iron therapy and ESA were administered intravenously according to the K/DOQI guidelines in order to maintain transferrin saturation between 20 and 40%, serum ferritin between 150 and 500 ng/ml and Hb between 11 and 12 g/dl. Qb, treatment time and Qd remained constant. Ol-HDF and hfHD were performed using membranes of size 1.9-2.1 sqm. Ultrapure dialysate and substitution fluid were employed in both HDF and HD treatments. Data are expressed as mean ± SD. Paired t test, Mann-Whitney U test, and simple and multiple regression analyses were employed for statistical evaluation. Results: Study group: total convective volume (TCV) was 22.1 ± 1.9 l/session. A significant reduction of hsCRP: from 6.8 ± 7.1 to 2.3 ± 2.4 mg/dl (p < 0.001), β₂M: from 36.5 ± 14.4 to 24.7 ± 8.6 mg/dl (p < 0.0001) and ESAdose: from 107 ± 67 to 65 ± 44 U/kg/week (p < 0.005) was observed. No significant variations of Hb, BW and sAlb were seen. A significant inverse correlation was found between TCV and Δβ₂M (r = -0.627; p < 0.0001), and TCV and ΔhsCRP (r = -0.514; p < 0.0001); no correlation between TCV and ΔESAdose was observed. No correlation was found between eKt/V and Δβ₂M, ΔhsCRP, and ΔESAdose. Multiple regression analysis with ΔESAdose as dependent variable showed ΔhsCRP as the only significantly associated independent factor (p < 0.01). Control group: no significant variations of hsCRP, β₂M, and ESAdose were observed over time. Conclusions: Ol-HDF induces a long-term significant reduction in pre-dialysis β₂M and hsCRP concentrations. The magnitude of reduction is directly correlated to the amount of TCV achieved but not on eKt/V. The observed reduction in ESAdose requirement is independent either on convection or diffusion, but is directly associated to the concomitant reduction of inflammation.

Complementary effect of combination of statins with coenzyme q10 and omega-3 fatty acids in patients with combined dyslipidemia

s / Atherosclerosis 241 (2015) e149ee229 e207 EAS-0936. COMPLEMENTARY EFFECT OF COMBINATION OF STATINS WITH COENZYME Q10 AND OMEGA-3 FATTY ACIDS IN PATIENTS WITH COMBINED DYSLIPIDEMIA S. T oth, M. Sajty, T. Pek arov a, J. Feda cko, K. Spi s akov a, D. Pella. 1st Department of Internal Medicine, avol Jozef Saf arik University in Ko sice Faculty of Medicine, Kosice, Slovakia * Corresponding author. Introduction: Several studies have described a positive effect of statins and omega-3 PUFA or CoQ10 on cardiovascular system. The aim of this study was to determine the effect of this triple combination on various parameters associated with the progression of cardiovascular disorders. Material and methods: 90 patients taking statins at a dose, which allowed target LDL levels, but with remained elevated TG levels (1.5-4.5 mmol/L) were randomized into three groups (each N1⁄430). In the placebocontrol group we indicated continued administration of statins. In the groups with additive treatment patients continued use of statins in combination with omega-3 PUFA 3 g/day respectively omega-3 PUFA 3 g/ day and 200 mg CoQ10/day during three months. After 3 months (± 1 week), we performed a final examination and collection of samples. We observed the lipid profile (total cholesterol, HDL, LDL, TG), hsCRP levels, activity SOD and GPx and presence of negative pleiotropic effects of statins. Results: Combination of statins with omega-3 PUFA significantly reduced TG and increased HDL levels. Significant reduction of hsCRP and increse of GTx and SOD was detected as well. Triple combination significantly decreased LDL and increased HDL in compare to control and dual combination. hsCRP significantly decreased in compare to control and dual combination group. SOD significantly increased in compare to control and dual combination group and GPx in compare to control. Conclusion: According to our study we suggest positive and complementary effect of combined therapy on lipid parameters, endothelial function and some negative pleiotropic effects of statins. EAS-0948. STATINS IMPACT IN A PORTUGUESE PRIMARY CARE UNIT J. Frutuoso. Internal Medicine, Hospital Jos e Joaquim Fernandes, Beja,

The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: A multicenter FDG-PET trial

ObjectivesThis study evaluated the effect of p38 mitogen-activated protein kinase (p38MAPK) inhibitor, BMS-582949, on atherosclerotic plaque inflammation, using 18FDG-PET imaging. p38MAPK is an important element of inflammatory pathways in atherothrombosis and its inhibition may lead to reduced inflammation within atherosclerotic plaques. MethodsSubjects with documented atherosclerosis (n = 72) on stable low-dose statin therapy and having at least one lesion with active atherosclerotic plaque inflammation in either aorta or carotid arteries were randomized to BMS-582949 (100 mg once daily), placebo, or atorvastatin (80 mg once daily), for 12 weeks. Arterial inflammation was assessed using 18FDG-PET/CT imaging of the carotid arteries and aorta. Uptake of arterial 18FDG was assessed as target-to-background ratio (TBR): 1) as a mean of all slices of the index vessel, and 2) within active slices of all vessels (AS: which includes only slices with significant inflammation (TBR ≥ 1.6) at the baseline). ResultsTreatment with BMS-582949 did not reduce arterial inflammation relative to placebo, (ΔTBR index: 0.10 [95% CI: −0.11, 0.30], p = 0.34; ΔTBR AS: −0.01 [−0.31, 0.28], p = 0.93) or hs-CRP (median %ΔCRP [IQR]: 33.83% [153.91] vs. 16.71% [133.45], p = 0.61). In contrast, relative to placebo, statin intensification was associated with significant reduction of hs-CRP (%ΔCRP [IQR]: −17.44% [54.68] vs. 16.71% [133.45], p = 0.04) and arterial inflammation in active slices (ΔTBRAS = −0.24 [95% CI: −0.46, −0.01], p = 0.04). ConclusionsThe findings of this study demonstrates that in stable atherosclerosis, 12 weeks of treatment with BMS-582949 did not reduce arterial inflammation or hs-CRP compared to placebo, whereas intensification of statin therapy significantly decreased arterial inflammation.

A phase 2 randomized, double-blind, placebo-controlled study of the effect of VIA-2291, a 5-lipoxygenase inhibitor, on vascular inflammation in patients after an acute coronary syndrome

ObjectiveArachidonate 5-lipoxygenase (5-LO) is a key enzyme in the synthesis of leukotrienes. VIA-2291 is a potent 5-LO inhibitor, which has been shown to reduce hsCRP and noncalcified coronary plaque volume following an acute coronary syndrome (ACS). We aim to evaluate the effect of VIA-2291 on vascular inflammation compared to placebo using FDG-PET. MethodsA Phase II, randomized, double-blind, parallel-group study was conducted in 52 patients with recent ACS assigned 1:1 to either 100 mg VIA-2291 or placebo for 24 weeks. The primary outcome was the effect of VIA-2291 relative to placebo on arterial inflammation detected by 18fluorodeoxyglucose positron emission tomography (FDG-PET) within the index vessel after 24 weeks of daily treatment, compared to baseline. ResultsVIA-2291 was relatively well tolerated and was associated with a significant inhibition of the potent chemo-attractant LTB4, with a mean inhibition of activity of 92.8% (p < 0.0001) at 6 weeks in the VIA-2291 group, without further significant change in inhibition at 24 weeks. However, for VIA-2291 was not associated with significant difference in inflammation (target-to-background ratio) compared to placebo at 24 weeks or 6 weeks of treatment. Further, VIA-2291 was not associated with a significant reduction in hsCRP from baseline after either 6 or 24 weeks of treatment. ConclusionsVIA-2291 is well-tolerated and effectively reduces leukotriene production. However, inhibition of 5-LO with VIA-2291 is not associated with significant reductions in vascular inflammation (by FDG-PET) or in blood inflammatory markers. Accordingly, this study does not provide evidence to support a significant anti-inflammatory effect of VIA-2291 in patients with recent ACS.

Therapeutic effect of aripiprazole in chronic schizophrenia is accompanied by anti-inflammatory activity

BackgroundWeight gain and metabolic abnormalities occur in chronic schizophrenia patients treated with atypical antipsychotics. The purpose of the study was to evaluate changes in serum levels of C-reactive protein (CRP), insulin and cytokines (IL-6, TNF-α, IL-1β, IFN-γ, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-β1, IL-4, and IL-10) after switching to aripiprazole. MethodsCytokine, hsCRP and insulin measurements were performed in patients (n=17) on day 0 and day 28 of the study using standard ELISA assays. The psychopathological status was assessed using PANSS. WC and BMI were measured and calculated, respectively. ResultsWe observed high clinical efficacy in aripiprazole linked to a 2.7% weight loss. There were statistically significant reductions in PANSS scores and body parameters (p<0.001). After 28 days we detected a significant reduction in hsCRP (p<0.001), insulin (p<0.001), IL-1β, IL-6, TNF-α, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-β1, IL-4 (p<0.001), IFN-γ (p<0.05) and a significant elevation of IL-10 (p<0.001). There was a significant negative correlation between IL-10 levels and PANSS positive, negative and total scores after the study (p=0.022, p=0.003, p=0.008, respectively). ConclusionsAripiprazole limits inflammatory processes by enhancing anti-inflammatory signaling. Aripiprazole also reduces the risk of metabolic abnormalities.

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.

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.

Antiatherosclerotic potential of aliskiren: its antioxidant and anti-inflammatory effects in rabbits: a randomized controlled trial

Background: Aliskiren is a direct renin inhibitor. It counteracts renin-angiotensin system and is used to treat hypertension. This study aims to evaluate the effect of aliskiren on the progression of atherosclerosis in domestic rabbits. Methods: Twenty-one local domestic rabbits were divided into three groups each group had special dietary regimen for 8 weeks: Group I (normal control), Group II (atherogenic control) and Group III (2% Cholesterol + aliskiren 40mg/kg/day orally). Blood samples were collected at the end of experiment (8 weeks) for measurement of serum lipid profile, plasma high sensitive C-reactive protein (hs-CRP), plasma malondialdehyde (MDA) and plasma reduced glutathione (GSH). Immunohistochemical analysis including vascular cell adhesion molecule-1 (VCAM-1); monocyte chemoattractant protein-1 (MCP-1); tumor necrotic factor - α (TNF-α); and interleukin – 17 (IL-17). Histopathologic assessment of aortic atherosclerotic changes were also performed. Results: Compared to normal control group, there is a significant increase in the level of lipid profile, hs-CRP (134.1±1.2ug/L), and malondialdehyde (0.561±0.136umol/L) in the atherogenic diet group, while GSH was significantly reduced (0.58±0.024mmol/L) at (p ≤ 0.05). Immunohistochemical analysis showed that expression of aortic VCAM-1; MCP-1; TNF-α; and interleukin–17 were significantly increased in atherogenic control group compared to normal control group (p<0.001). In addition, animals on atherogenic diet have significant atherosclerotic lesion compared to normal control group. Aliskiren group appears to have no significant effect on lipid profile compared to atherogenic control group, but it has statistically significant reduction in hs-CRP (73.1±3.88ug/L) and MDA (0.261±0.15umol/L) at (p ≤ 0.05). Aliskiren treatment failed to significantly increase the level of plasma reduced glutathione. In addition, aliskiren treatment significantly reduced the expression of VCAM-1; MCP-1; TNF-α; and IL–17 (p≤0.05). Histopathological examination of aortic arch showed that aliskiren significantly reduced atherosclerotic lesion (p≤0.005). Conclusion: We can conclude that aliskiren is helpful in reducing lipid peroxidation, systemic inflammation and aortic expression of inflammatory markers used in this study and hence reduces the progression of atherosclerotic plague.

Monteleucast and Zileuton Retard the Progression of Atherosclerosis via Down Regulation of the Inflammatory and Oxidative Pathways

Background: Atherosclerosis and its thrombotic complications are responsible for remarkably high numbers of deaths. Leukotrines are involved in different stages of atherosclerosis. Therefore this study was undertaken to evaluate the effect of montelukast and zileuton on the progression of atherosclerosis. Materials and methods: Thirty-five male rabbits were used in this study. These animals randomized into 5 groups (7 rabbits each). Rabbits in first group were maintained on normal rabbit chow diet and used as normal diet control group (NC). While the rabbits in other four groups were fed on atherogenic diet (2% cholesterol) for 8 weeks. The second group, Atherogenic Control Group (AC) rabbits received atherogenic diet alone. Third group, Positive Control Group (PC) rabbits received atherogenic diet and ethanol as vehicle. Forth group, Montelukast Treated Group (MT) rabbits received montelukast 1.5 mg per kg daily and the fifth group, Zileuton Treated Group (ZT) rabbits received zileuton 150 mg per kg daily. At the end of 8th weeks animals were sacrificed, blood sample was collected to measure the following parameters: lipid profile, plasma GSH, MDA, and hsCRP. Immunohistochemical analysis (VCAM-1, MCP-1, TNF-α, and IL17) and histopathologic assessment of aortic atherosclerotic changes were also performed. Results: Compared to NC, levels of lipid profile, atherogenic index, hsCRP, and MDA are increased while GSH were decreased in animals on atherogenic diet (p<0.001). There was statistically insignificant difference in the study parameters between positive control groups, when compared with those on atherogenic diet. Immunohistochemical analysis showed that expression of aortic VCAM-1, MCP-1, TNF-α and IL17 were significantly increased in AC group compared to NC group (p<0.001). Histopathologic finding showed that animals on atherogenic diet have significant atherosclerotic lesion compared to NC group. Compared to AC group both montelukast and zileuton do not have significant effect on lipid profile. Montelukast and zileuton cause statistically significant reduction in hsCRP and MDA, (p<0.001). Montelukast and zileuton treatment caused statistically significant, increase in plasma levels of GSH and reduced plasma MDA level (p<0.001). Both montelukast and zileuton treatment significantly reduced the expression of aortic VCAM-1, MCP-1, TNF-α and IL17 (p<0.001). Histopathologic examination of aortic arch showed that both montelukast and zileuton significantly reduced atherosclerotic lesion (p<0.001). Conclusion: Both montelukast and zileuton reduce lipid peroxidation, systemic inflammation and aortic expressions of inflammatory markers used in this study and reduced the progression of atherosclerosis.

256: Ramadan fasting and high sensitive CRP in patients with stable coronary artery disease: a pilot study

Ramadan fasting is one of the five pillars observed by Muslim adults worldwide. Data on incidence of acute coronary syndrome during fasting Ramadan are scarce and conflicting. Inflammation plays a major role in atherothrombosis, and measurement of cardiac biomarkers such as High sensitive C-reactive protein (hs-CRP) may provide a strong independent predictor of future cardiac events. was to evaluate the effect of fasting during Ramadan on hs-CRP in patients with stable coronary artery disease (CAD). it was a prospective pilot study among 27 patients with stable CAD (within the last 6 months) who were observed before and at the end of Ramadan fasting. Patients were recruited from outpatients department. Twenty one were males and 6 were females with a mean age of 59±8.2 years (52-75 y). Fifteen patients had hypertension, 10 were smokers and 7 were diabetics. Blood was analyzed at the first visit was a week before the onset of Ramadan and the second visit at the third week of Ramadan. The assay of hs-CRP was done with the collected sera by Demeditec Diagnostics Systems Laboratories (Germany). Six patients were excluded for the second visit due to various reasons (break voluntary of fasting in two cases, 4 patients with concurrent inflammatory disorders e.g. rheumatoïd disease in 2 cases and intercurrent infections in two others). A total of 21 subjects were screened during this period. There was a significant reduction in hs-CRP during Ramadan compared before this period: 6.6±8.7 vs 3.8±5.5 (p <0.0001). The mean variation of hs-CRP during this holy period was – 39.3±– 20.9 (0% à – 68.3%). The hs-CRP level was less than 3 mg/l in 10 patients (47.6%) before compared to 13 pts (62%) during Ramadan. The reduction of hs-CRP was independent of the risk factors or the dosage of statins. The practice of fasting during the month of Ramadan by the people with stable CAD might be cardio-protective as it resulted in the lowering of hs-CRP.

Effects of long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study

We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T < 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm2; femoral BMD= 0.847 ± 0.117 g/cm2). TU induced a significant improvement of bone mass after 36 months (lumbar BMD = 1.053 ± 0.145 g/cm2; p < 0.002; femoral BMD = 0.989 ± 0.109; p < 0.003 g/cm2) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r2 = 0.66, p < 0.0001) and femoral (r2 = 0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middle-aged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications.

Effects of rosuvastatin on vascular biomarkers and carotid atherosclerosis in lupus: A randomized, double‐blind, placebo‐controlled trial

To study the effect of rosuvastatin on vascular biomarkers and carotid intima-media thickness (IMT) in systemic lupus erythematosus (SLE). SLE patients with inactive disease and subclinical atherosclerosis were randomized in a double-blinded manner to receive either rosuvastatin (10 mg/day) or matching placebo (half in each group were also randomly allocated low-dose aspirin). After 12 months, treatment was unblinded. Patients treated with rosuvastatin and aspirin were continued on the same medications for another 12 months. Plasma levels of homocysteine, high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule 1, P-selectin, and thrombomodulin were measured at baseline, 6 months, and 12 months. Measurement of carotid IMT was repeated at 24 months. Seventy-two patients were studied (97% women, mean ± SD age 50.8 ± 9.7 years). Thirty-six patients were randomly assigned to each of the study arms (18 patients in each arm also received aspirin). Baseline clinical characteristics and medications were similar between the two groups. At 12 months, the mean low-density lipoprotein cholesterol (mean ± SD 2.62 ± 1.04 mmoles/liter to 1.69 ± 0.72 mmoles/liter; P < 0.001) and median hsCRP levels (1.26 mg/liter, interquartile range [IQR] 2.3 to 0.88 mg/liter, IQR 1.1; P = 0.02) decreased significantly in the rosuvastatin group. There was no significant change in homocysteine, and aspirin use did not influence the levels of the biomarkers studied. A subgroup analysis of patients with a Systemic Lupus Erythematosus Disease Activity Index score ≤2 revealed a significant decrease in hsCRP (1.20 mg/liter, IQR 2.3 to 0.92 mg/liter, IQR 1.1; P = 0.04) and thrombomodulin levels (0.76 ng/ml, IQR 1.2 to 0.67 ng/ml, IQR 1.0; P = 0.001) with rosuvastatin treatment. At 24 months, the IMT of the internal carotid arteries appeared to be decreased in patients treated with rosuvastatin, which was well tolerated. In stable SLE patients, low-dose rosuvastatin leads to a significant reduction in hsCRP and thrombomodulin levels, which may possibly help to reduce cardiovascular risk.

Effect of orange juice and beverage with phytosterols on cytokines and PAI-1 activity

Inflammation is pivotal in all phases of atherosclerosis. Dietary options which lower inflammatory biomarkers would be an attractive strategy to reduce risk from cardiovascular diseases and cancer. Indeed, fruit and vegetable intake or fruit juice consumption is associated with health and wellness. However, there is a paucity of data examining the effect of orange juice on biomarkers of inflammation in healthy volunteers. We have previously conducted the first placebo-controlled randomized studies examining the effect of sterol fortified orange juice or sterol fortified reduced calorie orange juice beverage supplementation (2g sterols/day) compared to Placebo OJ or Placebo OJBev, and showed significant benefits on the lipid profile as well as significant reduction in hsCRP, the prototypic marker of inflammation and a cardiovascular risk marker. The aim of this study was to examine the effect of orange juice (OJ) or OJ beverage (Bev) alone and fortified with plant sterols (1g/240ml juice or beverage twice a day) on pro-inflammatory cytokines and PAI-1, a marker of impaired fibrinolysis in healthy human volunteers. In the first study, 72 healthy human volunteers received Placebo OJ or Sterol OJ and in the second study, 72 volunteers received OJBev or Sterol OJBev for 8 weeks and blood was drawn at baseline and following supplementation for 8 weeks. Biomarkers of Inflammation (IL-1b, IL-6, TNF, IL-8, IL-10) were assessed in serum using the BD Human Inflammatory Cytokine Cytometric Bead Array and PAI-1 activity was assessed in citrated plasma. OJ or OJBev alone failed to result in any significant effects on circulating cytokine levels or PAI-1 activity. There was a significant reduction in IL-1b with sterol fortified OJ (p<0.05) compared to baseline. In addition, both sterol fortified OJ as well as sterol fortified OJBev resulted in significant reductions in serum IL-6 levels (p<0.01). Thus, sterol fortified OJ and OJ Beverage are able to effectively lower biomarkers of inflammation in healthy human volunteers in addition to providing lipid profile benefits and may thus contribute to decreasing cardiovascular risk.

Ramadan Fasting And Cardiac Biomarkers In Patients With Multiple Cardiovascular Disease Risk Factors

Objectives: The study was aimed to evaluate the effect of fasting during Ramadan on cardiovascular bio-markers [high sensitive C reactive protein (hs-CRP), plasminogen activator inhibitor type-1 (PAI-1)] with other conventional cardiovascular risk factors like diabetes (DM), hypertension (HPT) and dyslipidaemia before, during and after Ramadan of the subjects under study. Methodology: It was a prospective cohort study with 76 subjects (41 males and 35 females) who were observed before during and after Ramadan.).At each visit anthropometric parameters were measured including the body weight, body mass index (BMI) and blood pressure. Blood was analyzed for metabolic index [fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c) and fasting serum lipids], hs-CRP and PAI-1.More than 50% of the subjects under study had 4 risk factors such as DM, HPT, dyslipidaemia and either family history of CAD or smoking. Results: A significant reduction of hs-CRP and PAI-1 was observed during Ramadan compared to pre-Ramadan (p < 0.001 and 0.031). The reduction of PAI-1 levels was continued till post-Ramadan (p = 0.005). A rebound in the levels of hs-CRP was observed in post-Ramadan compared to Ramadan (p < 0.001).Significant (p<.001) reduction of the body weight, BMI, systolic and diastolic blood pressure was observed during Ramadan compared to pre-Ramadan and post-Ramadan. LDL-C levels were reduced during and post-Ramadan, (p = 0.037 and p = 0.030), however, no significant effect on triglyceride and total cholesterol was found throughout the study. Conclusion: The practice of fasting during the month of Ramadan by the people with multiple CVD risks might be cardio-protective as it resulted in the lowering of both hs-CRP and PAI-1. However this benefit is short-lived as the hs-CRP rebound a month later. Ramadan fasting practice was found to give short-term benefit against cardiovascular diseases among the patients with multiple cardiovascular risks factors.

Increased inflammatory Response in Patients With Dilated Cardiomyopathy Is Associated With Dyslipidemia: Effects of Statin Therapy

Dilated cardiomyopathy (DCM) is associated with increased inflammatory response reflected among other markers in high-sensitivity C-reactive protein (hsCRP) and soluble interleukin-2 receptor (sIL-2R) levels. We examined prospectively 60 consecutive patients with DCM. Of them, 30 were dyslipidemic (group I) and 30 normolipidemic (group II). Group I patients were randomized to either simvastatin therapy (20 mg/day, group Ia, n = 15) or hypolipidemic diet therapy (group Ib, n = 15). Patients were re-evaluated 6 months later. High-sensitivity C-reactive protein and sIL-2R levels were significantly higher in group I compared with group II patients (19.5 ± 3.4 vs 3.03 ± 3.5 mg/L, P = .01, 1137 ± 441 vs 599 ± 235 pg/mL, P = .001, respectively). There was a significant correlation between sIL-2R and hsCRP levels in dyslipidemic patients but not in normolipidemic patients. Significant reduction of hsCRP and sIL-2R levels was observed only in group Ia patients. Patients with DCM having dyslipidemia have increased inflammatory response, which is reduced after 6 months of statin therapy.

The Influence of Cardiac Rehabilitation on Inflammation and Metabolic Syndrome in Women With Coronary Heart Disease

Metabolic syndrome (MetS) and increased inflammatory markers, both predictors of future cardiovascular events, are more prevalent in women with coronary heart disease (CHD). The influence of cardiac rehabilitation (CR) on MetS and inflammatory biomarkers is not well characterized for women. : The purpose of this article was to examine the effects of a 12-week behaviorally enhanced CR exclusively for women compared with traditional CR on components of the MetS and inflammatory markers in women with CHD. The randomized clinical trial used 2 treatment groups, both receiving a comprehensive 12-week CR program, with 1 group receiving a motivationally enhanced intervention exclusively for women. A subset of 91 women (mean age, 61.6 years) from the parent study provided serum samples to examine the effects of CR on high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and intercellular adhesion molecule-1 (ICAM-1). After CR, the total sample of women demonstrated significant reductions in hsCRP (P =.002), IL-6 (P <.001), TNF-alpha (P =.010), and ICAM-1 (P =.016). Women in the gender-tailored CR program significantly improved all biomarker levels compared with baseline (P <.05 for all), whereas those in the traditional group improved only hsCRP (P <.05) and IL-6 (P <.05) levels. The combined study group demonstrated improvements in several components of MetS (triglycerides, waist circumference, and systolic blood pressure) but not in others (high-density lipoprotein cholesterol, fasting glucose, and diastolic blood pressure). Cardiac rehabilitation promotes greater improvements in inflammatory biomarkers than in components of MetS for women with CHD. Improvements in body composition or weight may not be a precondition for the benefits of exercise because of loss of abdominal fat. Examining components of MetS as continuous variables is recommended to prevent lost information inherent in dichotomization.

Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss

Background and aims We investigated the effect of different exercise modalities on high sensitivity-C reactive protein (hs-CRP) and other inflammatory markers in patients with type 2 diabetes and the metabolic syndrome. Methods and results Eighty-two patients were randomized into 4 groups: sedentary control (A); receiving counseling to perform low-intensity physical activity (B); performing prescribed and supervised high-intensity aerobic (C) or aerobic + resistance (D) exercise (with the same caloric expenditure) for 12 months. Evaluation of leisure-time physical activity and assessment of physical fitness, cardiovascular risk factors and inflammatory biomarkers was performed at baseline and every 3 months. Volume of physical activity increased and HbA 1c decreased in Groups B–D. VO 2max, HOMA-IR index, HDL-cholesterol, waist circumference and albuminuria improved in Groups C and D, whereas strength and flexibility improved only in Group D. Levels of hs-CRP decreased in all three exercising groups, but the reduction was significant only in Groups C and D, and particularly in Group D. Changes in VO 2max and the exercise modalities were strong predictors of hs-CRP reduction, independent of body weight. Leptin, resistin and interleukin-6 decreased, whereas adiponectin increased in Groups C and D. Interleukin-1β, tumor necrosis factor-α and interferon-γ decreased, whereas anti-inflammatory interleukin-4 and 10 increased only in Group D. Conclusion Physical exercise in type 2 diabetic patients with the metabolic syndrome is associated with a significant reduction of hs-CRP and other inflammatory and insulin resistance biomarkers, independent of weight loss. Long-term high-intensity (preferably mixed) training, in addition to daytime physical activity, is required to obtain a significant anti-inflammatory effect.

Rosiglitazone increases bioactive testosterone and reduces waist circumference in hypogonadal men with type 2 diabetes

The purpose of this study was to assess the effect of rosiglitazone on bioavailable, free and total testosterone levels in hypogonadal men with type 2 diabetes. Sixteen type 2 diabetic men with hypogonadism were studied before and after administration of rosiglitazone (8 mg/day) for six months, with assessments performed every two months on two consecutive days. We measured testosterone and sex hormone binding globulin (SHBG), visceral adiposity, high-sensitivity CRP (hs-CRP), lipids, microalbuminuria and blood pressure. There was a significant increase in free (p=0.01), bioavailable (p=0.007) and total testosterone (p=0.002), as well as SHBG (p=0.03) levels, with rosiglitazone treatment. Waist circumference and waist / hip ratio decreased with the improvement in insulin sensitivity and glycaemic control (p=0.01). There was also a significant reduction in hs-CRP (p=0.02) and urinary albumin excretion. No significant effect on blood pressure or the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL to HDL) was seen. In conclusion, the insulin-sensitiser rosiglitazone increases bioavailable, free and total testosterone and SHBG levels in hypogonadal men with type 2 diabetes.

Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients

Recent studies showed that tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), as well as high-sensitive C-reactive protein (hsCRP) levels are predictive factors of cardiovascular risk. However, the effect of cardiac rehabilitation (CR) intervention in coronary artery disease (CAD) patients on these factors is not known. The aim of this study was to evaluate the effects of CR and exercise on hsCRP and inflammatory cytokine levels in patients with CAD after percutaneous coronary intervention (PCI). CAD patients who underwent PCI were divided into a CR and exercise group (CRE, n = 29) or a control group (CON, n = 10). CR and exercise consisted of 6 weeks supervised exercise training and 8 weeks home-based, self-managed exercise. Compared to pre-experimental levels, TNF-alpha (by 20.4%; p = 0.006) and IL-6 (by 49.0%; p < 0.0001), as well as hsCRP (by 59.4%; p < 0.0001), were markedly decreased after CR and exercise in CAD patients but not in control group, except for IL-6 (by 41.6%; p = 0.001). However, there was no significant alteration of adiposity-related variables such as BMI, percent body fat, and waist circumferences, in both groups. We suggest that CR and exercise in CAD patients after PCI induce significant reduction in hsCRP and inflammatory cytokines (TNF-alpha and IL-6), and marked increase in exercise tolerance and capacity.