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Life Extension Magazine April 2014

C-reactive protein

Impaired endothelial function in lone atrial fibrillation.

BACKGROUND/AIM: Impaired endothelial function has been previously documented in patients with atrial fibrillation (AF) and underlying comorbidities or older patients with idiopathic AF. The aim of this study was to evaluate systemic endothelial function in younger AF patients (less than < 60 years old) with lone AF (that is, without associated cardiopulmonary comorbidities, including arterial hypertension), by comparing brachial artery flow-mediated dilation (FMD) in lone AF patients with FMD of healthy subjects in sinus rhythm. METHODS: Two groups of participants were prospectively enrolled. The first group comprised of 38 AF patients (the mean age 45 +/- 11 years, 68% male) with persistent (> 7 days) lone AF. The second group comprised of 28 healthy controls in sinus rhythm (the mean age 43 +/- 13, 53% male), matched by age, gender and atherosclerotic risk factors. All the participants underwent physical examination, laboratory analysis [including determination of C-reactive protein (CRP)], standard echocardiography and exercise-stress testing. Brachial artery FMD and endothelium independent dilation (NMD) were assessed with a high-resolution ultrasound probe and arterial diameters taken from 5 consecutive cardiac cycles were averaged for each measurement to accommodate to beat-to-beat flow variations in AF. RESULTS: There were no differences between the 2 groups regarding age, gender and most clinical, laboratory and echocardiographic characteristics (all p > 0.05), apart from the increased heart rate (p = 0.018), body mass index (p = 0.027), CRP levels (p = 0.007) and left atrial anteroposterior dimension (p < 0.001) in AF patients. FMD of AF patients [median value 5.0%, interquartile range (IQR) 2.87%-7.50%] was significantly lower (p < 0.001) than FMD of healthy controls (median value 8.85%, IQR 5.80%-12.50%), whereas there were no differences in median NMD values (p > 0.05). In the multivariate analysis, the independent FMD determinants in our study population were the presence of AF, smoking and total cholesterol levels (all p < 0.001). In patients with AF, the strongest independent FMD determinant was arrhythmia duration (p < 0.001), followed by smoking (p = 0.013) and total cholesterol levels (p = 0.045). CONCLUSIONS: Our findings confirm that sustained AF is associated with systemic endothelial dysfunction even in relatively young patients with no cardiovascular disorders or risk factors. AF is an independent contributor to lower FMD and a prolonged arrhythmia duration may confer the risk for more profound endothelial damage.

Vojnosanit Pregl . 2013 Oct;70(10):908-14

Validation of C-reactive protein levels as a prognostic indicator for survival in a large cohort of pancreatic cancer patients.

Background: Recent evidence indicates that the host inflammatory response has an important role in the tumour progression. Elevated C-reactive protein (CRP) levels have been previously associated with poor prognosis in several cancer types including small-scale studies in pancreatic cancer (PC) patients. The purpose of the present study was to validate the prognostic impact of plasma CRP levels at date of diagnosis on cancer-specific survival (CSS) in a large cohort of PC patients.Methods:Data from 474 consecutive patients with adenocarcinoma of the pancreas, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. CSS was analysed using the Kaplan-Meier method. To evaluate the prognostic significance of plasma CRP levels, univariate and multivariate Cox analyses were applied.Results:High plasma CRP levels at diagnosis were significantly associated with well-established prognostic factors, including high tumour stage and tumour grade and the administration of chemotherapy (P<0.05). In univariate analysis, we observed that a high plasma CRP level was a consistent factor for poor CSS in PC patients (hazard ratio (HR)=2.21; 95% confidence interval (CI)=1.68-2.92, P<0.001). In multivariate analysis, tumour stage, grade, administration of chemotherapy, a high neutrophil-lymphocyte ratio and the highest quartile of CRP levels (HR=1.60, 95% CI=1.16-2.21; P=0.005) were identified as independent prognostic factors in PC patients.Conclusion:In conclusion, we confirmed a significant association of elevated CRP levels with poor clinical outcome in PC patients. Our results indicate that the plasma CRP level might represent a useful marker for patient stratification in PC management.

Br J Cancer . 2014 Jan 7;110(1):183-8

Effects of creatine supplementation on oxidative stress and inflammatory markers after repeated-sprint exercise in humans.

OBJECTIVE: The goal of this study was to evaluate the effects of creatine (Cr) supplementation on oxidative stress and inflammation markers after acute repeated-sprint exercise in humans. METHODS: Twenty-five players under age 20 y were randomly assigned to two groups: Cr supplemented and placebo. Double-blind controlled supplementation was performed using Cr (0.3 g/kg) or placebo tablets for 7 d. Before and after 7 d of supplementation, the athletes performed two consecutive Running-based Anaerobic Sprint Tests (RAST). RAST consisted of six 35-m sprint runs at maximum speed with 10 sec rest between them. Blood samples were collected just prior to start of test (pre), just after the completion (0 h), and 1 h after completion. RESULTS: Average, maximum, and minimum power values were greater in the Cr-supplemented group compared with placebo (P < 0.05). There were significant increases (P < 0.05) in plasma tumor necrosis factor alpha (TNF-a) and C-reactive protein (CRP) up to 1 h after acute sprint exercise in the placebo-supplemented group. Malondialdehyde, lactate dehydrogenase (LDH), catalase, and superoxide dismutase enzymes also were increased after exercise in both groups. Red blood cell glutathione was lower after exercise in both groups. Cr supplementation reversed the increase in TNF-a and CRP as well as LDH induced by acute exercise. Controversially, Cr supplementation did not inhibit the rise in oxidative stress markers. Also, antioxidant enzyme activity was not different between placebo and Cr-supplemented groups. CONCLUSION: Cr supplementation inhibited the increase of inflammation markers TNF-a and CRP, but not oxidative stress markers, due to acute exercise.

Nutrition. 2013 Sep;29(9):1127-32

Additive effects of isoflavones and exercise training on inflammatory cytokines and body composition in overweight and obese postmenopausal women: a randomized controlled trial.

OBJECTIVE: Isoflavones and exercise have been shown to affect C-reactive protein (CRP) and body composition and to act synergistically on trunk and total fat mass (FM), glucose metabolism, and lean body mass in postmenopausal women with a body mass index higher than 25 kg/m. We hypothesized that exercise and isoflavone supplementation (Ex + ISO) could reduce inflammation in the same subpopulation of women. The objective of this study was to investigate if 6 months of mixed exercise combined with isoflavones could have greater effects on specific inflammatory markers than exercise alone in overweight or obese postmenopausal women. METHODS: Thirty-four postmenopausal women aged 50 to 70 years were randomly assigned to exercise and placebo (Ex + PLA; n = 15) or Ex + ISO (n = 19). At baseline and after 6 months, waist circumference, hip circumference, total FM, trunk FM, leg FM, and muscle mass index (MMI; = total fat free mass [kg] / height [m]) were assessed (dual-energy x-ray absorptiometry). Inflammatory markers (CRP, tumor necrosis factor-a [TNF-a], and interleukin-6) were obtained by enzyme-linked immunosorbent assay. T tests were used to compare groups at baseline. RESULTS: The Ex + PLA group showed significant changes in MMI (+0.33 kg/m, P ≤ 0.009) and FM compartments (waist circumference, -5.13 cm; % FM, -1.31%; P ≤ 0.001), whereas inflammation remained unchanged. However, the Ex + ISO group showed significant changes in total FM (-1.70 kg, P < 0.0001), FM compartments (hip circumference [-2.51 cm, P = 0.019], leg FM [-1.16 kg, P = 0.037], and trunk FM [-0.72 kg, P = 0.006]), MMI (+0.39 kg, P = 0.011), and inflammation (CRP, -1.14 mg/L, P = 0.029; TNF-a, +0.29 pg/mL, P = 0.010). CONCLUSIONS: Despite an increase in TNF-a, the use of isoflavones-when body weight remains stable-seems to enhance the beneficial effects of mixed-exercise training on body composition and CRP in overweight or obese postmenopausal women.

Menopause . 2013 Dec 30

L-Carnitine supplementation for adults with end-stage kidney disease requiring maintenance hemodialysis: a systematic review and meta-analysis.

BACKGROUND: A previous meta-analysis indicated that l-carnitine significantly increased hemoglobin and decreased the required erythropoietin dose in maintenance hemodialysis patients. OBJECTIVE: An updated systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to reevaluate effects of l-carnitine. DESIGN: The Cochrane Library, PubMed, and EMBASE databases (31 December 2012) were searched to identify RCTs that investigated effects of l-carnitine in adults with end-stage kidney disease that required maintenance hemodialysis. RESULTS: Forty-nine RCTs (1734 participants) were included. l-Carnitine significantly decreased serum low-density lipoprotein (LDL) (mean difference: -5.82 mg/dL; 95% CI: -11.61, -0.04 mg/dL) and C-reactive protein (CRP) (-3.65 mg/L; -6.19, -1.12 mg/L). There were no significant differences in triglycerides (-0.89 mg/dL; -29.32, 27.53 mg/dL), cholesterol (0.14 mg/dL; -6.15, 6.42 mg/dL), high-density lipoprotein (1.13 mg/dL; -2.44, 4.70 mg/dL), hemoglobin (0.68 g/dL; 0.14, 1.50 g/dL), hematocrit (2.04%; -1.39, 5.48%), albumin (1.65 g/L; -0.22, 3.51 g/L), or the required erythropoietin dose (-0.76 KU/wk; -1.75, 0.23 KU/wk). No adverse effects were reported. CONCLUSIONS: This meta-analysis failed to confirm the previous findings regarding the effects of l-carnitine on hemoglobin and the erythropoietin dose but showed that l-carnitine significantly decreased serum LDL and CRP. The extent of the decrease in LDL was not clinically relevant, whereas the significant decrease in CRP was both statistically and clinically relevant. However, the relevance of decrease in CRP with hard endpoints such as all-cause mortality and cardiovascular complications still remains to be clarified.

Am J Clin Nutr . 2014 Feb;99(2):408-22

Effect of multispecies probiotic supplements on metabolic profiles, hs-CRP, and oxidative stress in patients with type 2 diabetes.

Background: We are aware of no study that has indicated the effects of daily consumption of multispecies probiotic supplements on metabolic profiles, high-sensitivity C-reactive protein (hs-CRP), and oxidative stress in diabetic patients. Objective: This study was designed to determine the effects of multispecies probiotic supplements on metabolic profiles, hs-CRP, and oxidative stress in diabetic patients. Methods: This randomized double-blind placebo-controlled clinical trial was performed on 54 diabetic patients aged 35-70 years. Subjects were randomly assigned to take either a multispecies probiotic supplement (n = 27) or placebo (n = 27) for 8 weeks. The multispecies probiotic supplement consisted of 7 viable and freeze-dried strains: Lactobacillus acidophilus (2 × 10(9) CFU), L. casei (7 × 10(9) CFU), L. rhamnosus (1.5 × 10(9) CFU), L. bulgaricus (2 × 10(8) CFU), Bifidobacterium breve (2 × 10(10) CFU), B. longum (7 × 10(9) CFU), Streptococcus thermophilus (1.5 × 10(9) CFU), and 100 mg fructo-oligosaccharide. Fasting blood samples were taken at baseline and after intervention to measure metabolic profiles, hs-CRP, and biomarkers of oxidative stress including plasma total antioxidant capacity and total glutathione (GSH). Results: Between-group comparisons of fasting plasma glucose (FPG) revealed that consumption of probiotic supplements prevented a rise in FPG (+28.8 ± 8.5 for placebo vs. +1.6 ± 6 mg/dl for probiotic group, p = 0.01). Although a significant within-group increase in serum insulin and low-density lipoprotein cholesterol levels was found in both the probiotic group and the placebo group, the changes were similar between the two groups. We observed a significant increase in HOMA-IR (homeostasis model of assessment-insulin resistance) in both the probiotic group (p = 0.02) and the placebo group (p = 0.001); however, the increase in the placebo group was significantly higher than that in the probiotic group (+2.38 vs. +0.78, p = 0.03). Mean changes in serum hs-CRP were significantly different between the two groups (-777.57 for the probiotic group vs. +878.72 ng/ml for the placebo group, p = 0.02). Probiotic supplementation led to a significant increase in plasma GSH levels compared to placebo (240.63 vs. -33.46 µmol/l, p = 0.03). Conclusion: In conclusion, multispecies probiotic supplementation, compared with placebo, for 8 weeks in diabetic patients prevented a rise in FPG and resulted in a decrease in serum hs-CRP and an increase in plasma total GSH.

Ann Nutr Metab . 2013;63(1-2):1-9

Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease.

OBJECTIVE: The n-3 polyunsaturated fatty acids are dietary components derived from fish oil with beneficial cardiovascular effects that may relate in part to anti-inflammatory properties. Peripheral artery disease (PAD) is characterized by a marked proinflammatory state. We hypothesized that the n-3 polyunsaturated fatty acids content of red blood cells (omega-3 index) would be correlated with biomarkers of inflammation and vascular function in a PAD cohort. METHODS: This was a cross-sectional study of subjects who presented to an outpatient vascular surgery clinic for evaluation of PAD. We used linear regression to evaluate the independent association between the omega-3 index, inflammatory biomarkers (C-reactive protein [CRP], intercellular adhesion molecule-1, interleukin-6, and tumor-necrosis-factor-a) and endothelial function (brachial artery flow mediated dilation). RESULTS: 64 subjects (61 claudicants and three with critical limb ischemia) were recruited for the study. The mean CRP level was 5.0 ± 5.0 mg/L, and the mean omega-3 index was 5.0% ± 1.8%. In an unadjusted model, the omega-3 index was negatively associated with CRP (38% increase in CRP for one standard deviation decrease in the omega-3 index; P = .007), which remained significant after adjustment for age, body mass index, smoking, ankle-brachial index, and high-density lipoprotein (33%; P = .04). There was also evidence for independent associations between the omega-3 index and IL-6 (P = .001). There were no significant associations between the omega-3 index and vascular function tests. CONCLUSIONS: In a cohort of patients with PAD, the omega-3 index was inversely associated with biomarkers of inflammation even after adjustment for covariates including the ankle-brachial index. Because patients with PAD have a high inflammatory burden, further studies should be conducted to determine if manipulation of omega-3 index via dietary changes or fish oil supplementation could improve inflammation and symptoms in these patients.

J Vasc Surg . 2013 Nov;58(5):1283-90

Effect of zinc supplementation on inflammatory markers and adipokines in young obese women.

Obesity is a chronic inflammatory state characterized by altered adipokine production and increased levels of inflammatory cytokines. The study explored the effect of zinc supplementation on inflammatory markers and adipocyte hormones in young obese women. Twenty five non-obese women and forty obese women (body mass index ≥25 kg/m(2)) aged 19-28 years were recruited for this study. Twenty obese women of the study group took 30 mg/day of supplemental zinc as zinc gluconate for 8 weeks and 20 obese women of control group took placebo. Usual dietary zinc intake was estimated from 3-day diet records. Serum zinc and urinary zinc concentration were measured by Atomic Absorption Spectrophotometry. Inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-a), and interleukin (IL)-6 and adipocyte hormones such as lepin and adiponectin were measured by enzyme immunoassay. Inflammatory markers and leptin were significantly higher, but adiponectin was significantly lower in obese women than non-obese women. Zinc supplementation increased serum zinc by 15 % and urinary zinc by 56 % (P < 0.05). The levels of hs-CRP (P = 0.03) and IL-6 (P = 0.006) significantly decreased with zinc supplementation, but not in placebo group. Serum leptin and plasma adiponectin concentration did not differ with either zinc supplementation or placebo. The levels of IL-6 and leptin were inversely associated with dietary zinc intake. These results suggest that zinc may have a favorable effect on obesity-related inflammation in young adults.

Biol Trace Elem Res . 2014 Feb;157(2):101-6

Effect of high-dose zinc supplementation with oral hypoglycemic agents on glycemic control and inflammation in type 2 diabetic nephropathy patients.

OBJECTIVE: The study aims to evaluate the effect of zinc sulfate on markers of glycemic control, lipid profile and inflammation in type 2 diabetes with microalbuminuria patients. MATERIALS AND METHODS: Type 2 diabetes with microalbuminuria patients on oral hypoglycemic agents (OHA) and angiotensin converting enzyme (ACE) inhibitors were selected and divided into 2 groups: One group (n = 27) continued with OHA alone, second group (n = 27) was on OHA and in addition 50 mg elemental zinc as zinc sulphate supplementation for 12 weeks. Fasting, post-prandial blood glucose, glycosylated hemoglobin, lipid profiles, inflammatory marker hs-CRP and urine microalbumin were measured. RESULTS: There were no significant differences in biochemical status among groups at baseline. After receiving zinc, the mean fasting blood glucose (FBS), post-prandial blood glucose (PPBS) and glycosylated hemoglobin (HbA1c) were decreased significantly (P = 0.0001). Significant decrease was observed in TG (P = 0.002) and VLDL-cholesterol (P = 0.002), whereas there was no significant decrease in TC and LDL-cholesterol. The high-density lipoprotein (HDL) cholesterol was significantly (P = 0.0001) increased from baseline. Zinc supplementation had significant effects in decreasing serum hs-CRP from 10.51 ± 1.68 mg/L to 7.75 ± 1.56 mg/L (P = 0.0001) and microalbumin level from 146.87 ± 30.83 mg/day to 80.70 ± 33.99 mg/day (P = 0.0001). There were no significant changes in the levels of all these parameters in OHA group. CONCLUSION: Our results conclude that supplementation of zinc improved the effectiveness of OHA and may be beneficial in decreasing blood glucose, TG, urinary albumin excretion and inflammation in diabetic nephropathy patients and thus reducing the risk of complications.

J Nat Sci Biol Med . 2013 Jul;4(2):336-40

The role of C-reactive protein as an inflammatory marker in gastrointestinal diseases.

C-reactive protein (CRP) is an acute-phase protein that is produced in large amounts by hepatocytes, upon stimulation by the cytokines interleukin-6, tumor-necrosis-factor-alpha and interleukin-1beta, during an acute-phase response. CRP is an objective marker of inflammation and, in gastrointestinal diseases such as Crohn’s disease and acute pancreatitis, its levels correlate well with clinical disease activity. In contrast to its use as a marker in Crohn’s disease, however, CRP is a less reliable marker of inflammation and disease activity in patients with ulcerative colitis, except perhaps for severe, extensive colitis. The increased production of CRP after an acute-phase stimulus, such as active gut inflammation, might explain why strong anti-inflammatory agents, such as anti-tumor-necrosis-factor-alpha antibodies and other biologic agents, work particularly well in patients with increased levels of CRP. CRP is also useful as a laboratory marker to predict prognosis and relapse in patients with Crohn’s disease and acute pancreatitis. Elevated CRP levels have been associated with an increased risk of colorectal cancer and are a marker of poor prognosis, indicating more advanced disease and, possibly, reduced survival. An important question that remains is how often CRP levels should be measured. Until there are more data, the use of CRP and of other biomarkers should be seen as an additional tool that aids clinical observation and physical examination, but that cannot replace it.

Nat Clin Pract Gastroenterol Hepatol . 2005 Dec;2(12):580-6

Preliminary case-control study to evaluate diagnostic values of C-reactive protein and erythrocyte sedimentation rate in differentiating active Crohn’s disease from intestinal lymphoma, intestinal tuberculosis and Behcet’s syndrome.

BACKGROUND: There are few evidences of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) in differentiating active Crohn’s disease (CD) from intestinal lymphoma (IL), intestinal tuberculosis (ITB) and Behcet’s syndrome (BD). This study is designed to investigate potential differential capacity of the 3 biomarkers between these disorders. METHODS: A hospital-based case-control study was performed. A total of 29 active CD, 25 IL, 30 ITB and 17 BD patients were collected. Laboratory parameters were drawn from the first blood test results on admission. RESULTS: In active CD group, the level of CRP was 20.2 ± 4.26 mg/dL, which was statistically lower than IL (59.9 ± 10.8 mg/dL, P < 0.0001). Similarly, the level of ESR reached its lowest point in active CD group (23.8 ± 3.18 mm/hr), compared with 46.6 ± 6.46 mm/hr in IL group (P = 0.0002). CRP showed a possible diagnostic value in differentiation of IL from active CD (odds ratio = 1.028, P = 0.046). CRP also exhibited a superior ability (area under curve [AUC] = 0.821) than ESR (AUC = 0.797) and CRP+ESR (AUC = 0.800) in distinguishing active CD from IL. The optimal cutoff value was 19.7 mg/dL, and the sensitivity and specificity were 62.1% and 96.0%, respectively. CONCLUSIONS: A significant decreased level of CRP and ESR was confirmed in active CD compared with IL. Current study demonstrated a possible differential value of CRP between active CD and IL. Further studies would be performed to validate their clinical significances.

Am J Med Sci. 2013 Dec;346(6):467-72