BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) is characterized by an exceptionally high mortality rate, primarily due to cardiovascular disease. Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and CKD. DESIGN, PARTICIPANTS, & MEASUREMENTS: A cross-sectional study was conducted in 218 prevalent patients (121 men; 63 +/- 14 yr) undergoing hemodialysis (HD). sTWEAK levels in relation with the patients' outcome were studied. RESULTS: sTWEAK plasma levels were 208 [(165 to 272) pg/ml, median interquartile range], significantly lower than healthy controls (P 7.0 pg/ml), in whom high sTWEAK strongly predicted cardiovascular and all-cause mortality. These results were confirmed in a second cohort of HD patients. CONCLUSIONS: The concurrent presence of elevated sTWEAK plasma concentrations and an inflammatory environment have additive effects on mortality in HD patients. Further studies on the potential different role of sTWEAK in health and disease are warranted.
a-Defensins are part of the innate immune system. Low-grade inflammation seems to play a crucial role in development and progression of chronic heart failure (CHF). The aims of the present study were to compare plasma levels of a-defensins in CHF patients and healthy controls and to examine the predictive ability of a-defensins, alone and combined with N-terminal pro brain natriuretic peptide (NT-proBNP), with respect to all-cause mortality.
In a prospective observational study lasting 2.6 years we examined the prognostic value of plasma a-defensins with respect to mortality in 194 CHF patients, and compared plasma levels with those of 98 age-matched healthy controls. a-Defensin levels were twice as high among CHF patients in New York Heart Association (NYHA) functional class III-IV than in patients in NYHA class I-II and healthy controls (P = 0.001). The absolute increase in risk of mortality for patients with a-defensin levels in the upper tertile vs. the lowest tertile was 30% (P = 0.002). After adjusting for potential confounders including NT-proBNP, plasma a-defensins remained independently associated with an increased risk of all-cause mortality (hazard ratio 1.65, 95% confidence interval 1.19-2.28, P = 0.002) per 1 standard deviation increment in Ln (natural logarithm)-transformed a-defensin values. The combination of high a-defensins and NT-proBNP levels provided incremental prognostic information independent of well-known prognostic biomarkers in heart failure.
Plasma a-defensins appear to have prognostic information regarding mortality among patients with CHF and seem to provide incremental information to established clinical risk markers.
High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation.
Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher's Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network.
We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals.
This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations.
Cites: Ann Clin Res. 1973 Jun;5(3):109-414584134
Cites: Genome Biol. 2011;12(3):R2221410973
Cites: Nat Genet. 2006 Feb;38(2):218-2216429159
Cites: PLoS Genet. 2006 Aug 18;2(8):e13016934000
Cites: Am J Hum Genet. 2007 Jun;80(6):1024-3617503322
Cites: Am J Physiol Gastrointest Liver Physiol. 2007 Jul;293(1):G1-417218471
Cites: Diabetologia. 2008 Jan;51(1):62-917972059
Cites: Bioinformatics. 2008 Mar 1;24(5):719-2018024473
Cites: Genome Res. 2008 May;18(5):706-1618347327
Cites: Am J Hum Genet. 2008 Aug;83(2):180-9218674750
The purpose of this study was to describe levels of inflammation markers in Norwegian children and to examine the associations of adiposity, aerobic fitness, and muscle fitness with markers of inflammation.
In 2005-2006, 1467 nine-year-olds were randomly selected from all regions in Norway. The participation rate was 89%. The inflammatory markers evaluated included C-reactive protein (CRP), leptin, adiponectin, plasminogen activator inhibitor-1, tumor necrosis factor-a, hepatocyte growth factor, resistin, and interleukin-6. We assessed muscular strength by measuring explosive, isometric, and endurance strength. Aerobic fitness was measured directly during a maximal cycle ergometer test. Adiposity was expressed as waist circumference (WC).
The girls had significantly higher levels of CRP, leptin, adiponectin, and resistin and lower levels of tumor necrosis factor-a compared with the boys. We observed a graded association of CRP and leptin levels across quintiles of WC, aerobic fitness, and muscle fitness (P = 0.001 for all participants). The regression analyses revealed that WC, aerobic fitness, and muscle fitness were independently associated with the CRP (WC ß = 0.158, P
In the nonpregnant population, there is extensive evidence of a systemic low-grade inflammatory status in relation to excess adipose tissue. Less is known about the relation during pregnancy.
Our main objective was therefore to explore the effect of pregnancy on adiposity-related systemic inflammation.
This study is a longitudinal cohort study of 240 pregnant women of Scandinavian heritage at Oslo University hospital-Rikshospitalet, Norway from 2002 to 2005. The inflammatory markers (C-reactive protein [CRP], Interleukin-6 [IL-6], monocyte chemoattractant protein 1 [MCP-1], IL1-Ra, tumor necrosis factor receptor II, and IL-10) were measured at four timepoints during pregnancy and analyzed by enzyme immuno-assay. The women were categorized based on BMI at inclusion (BMI 30 kg/m(2)). Data were analyzed by Friedman-test, Wilcoxon signed rank test, or Kruskal-Wallis test as appropriate.
Maternal adiposity was associated with significantly higher circulatory levels of several inflammatory markers (CRP, MCP-1, IL-6, and IL-1Ra). However, this proinflammatory upregulation was not evident toward the end of pregnancy, as levels of CRP, MCP-1, and IL-6 were not any longer significantly different between the BMI categories.
Although normal pregnancy exhibits proinflammatory features, this does not seem to have additive or synergistic effects on the inflammation associated with adiposity. On the contrary, we found that the BMI-dependent increase in proinflammatory markers was not evident at the end of pregnancy.
Adult obesity and inflammation have been associated with risk of colorectal cancer (CRC); however, less is known about how adolescent body mass index (BMI) and inflammation, as measured by erythrocyte sedimentation rate (ESR), relate to CRC risk. We sought to evaluate these associations in a cohort of 239 658 Swedish men who underwent compulsory military enlistment examinations in late adolescence (ages 16-20 years).
At the time of the conscription assessment (1969-1976), height and weight were measured and ESR was assayed. By linkage to the national cancer registry, these conscripts were followed for CRC through 1 January 2010. Over an average of 35 years of follow-up, 885 cases of CRC occurred, including 501 colon cancers and 384 rectal cancers. Cox regression was used to estimate adjusted HRs and corresponding 95% CIs.
Particulate air pollution is associated with cardiovascular morbidity. One hypothesized mechanism involves oxidative stress, systemic inflammation, and endothelial dysfunction.
To assess an intervention's impact on particle exposures and endothelial function among healthy adults in a woodsmoke-impacted community. We also investigated the underlying role of oxidative stress and inflammation in relation to exposure reductions.
Portable air filters were used in a randomized crossover intervention study of 45 healthy adults exposed to consecutive 7-day periods of filtered and nonfiltered air.
Reactive hyperemia index was measured as an indicator of endothelial function via peripheral artery tonometry, and markers of inflammation (C-reactive protein, interleukin-6, and band cells) and lipid peroxidation (malondialdehyde and 8-iso-prostaglandin F(2a)) were quantified. Air filters reduced indoor fine particle concentrations by 60%. Filtration was associated with a 9.4% (95% confidence interval, 0.9-18%) increase in reactive hyperemia index and a 32.6% (4.4-60.9%) decrease in C-reactive protein. Decreases in particulate matter and the woodsmoke tracer levoglucosan were associated with reduced band cell counts. There was limited evidence of more pronounced effects on endothelial function and level of systemic inflammation among males, overweight participants, younger participants, and residents of wood-burning homes. No associations were noted for oxidative stress markers.
Air filtration was associated with improved endothelial function and decreased concentrations of inflammatory biomarkers but not markers of oxidative stress. Our results support the hypothesis that systemic inflammation and impaired endothelial function, both predictors of cardiovascular morbidity, can be favorably influenced by reducing indoor particle concentrations.
Exposure to particulate air pollution increases respiratory and cardiovascular morbidity and mortality, especially in elderly, possibly through inflammation and vascular dysfunction.
We examined potential beneficial effects of indoor air filtration in the homes of elderly, including people taking vasoactive drugs.Forty-eight nonsmoking subjects (51 to 81 years) in 27 homes were included in this randomized, double-blind, crossover intervention study with consecutive two-week periods with or without the inclusion of a high-efficiency particle air filter in re-circulating custom built units in their living room and bedroom. We measured blood pressure, microvascular and lung function and collected blood samples for hematological, inflammation, monocyte surface and lung cell damage markers before and at day 2, 7 and 14 during each exposure scenario.
The particle filters reduced the median concentration of PM2.5 from approximately 8 to 4 µg/m3 and the particle number concentration from 7669 to 5352 particles/cm3. No statistically significant effects of filtration as category were observed on microvascular and lung function or the biomarkers of systemic inflammation among all subjects, or in the subgroups taking (n = 11) or not taking vasoactive drugs (n = 37). However, the filtration efficacy was variable and microvascular function was within 2 days significantly increased with the actual PM2.5 decrease in the bedroom, especially among 25 subjects not taking any drugs.
Substantial exposure contrasts in the bedroom and no confounding by drugs appear required for improved microvascular function by air filtration, whereas no other beneficial effect was found in this elderly population.
Cites: Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H944-5318083905
Cites: Occup Environ Med. 2008 May;65(5):319-2417704195
BACKGROUND AND AIMS: Immigrant women from the Middle East have higher cardiovascular risk compared to native women. Whether low antioxidant intake, oxidative stress or inflammation contributes to risk is unknown. In a cross-sectional study of 157 randomly selected foreign-born women (Iranian and Turkish) and native women living in Sweden, we investigated antioxidant status, oxidative stress (F(2)-isoprostanes) and systemic inflammation (plasma high sensitive C-reactive protein; CRP) markers. We also investigated relationships between F(2)-isoprostanes, CRP and cardiovascular risk factors. METHODS AND RESULT: Dietary intake was assessed using 24-h dietary recalls repeated four times. Micronutrient intake was not consistently different between groups. Serum alpha-tocopherol, but not gamma-tocopherol levels, was lower in Turkish vs. Swedish women (P0.21, P values