Markers of inflammation and their clinical significance.
ABSTRACT Inflammation plays an important role in the initiation and progression of atherosclerosis and the development of atherosclerotic events. Understanding the molecular basis of inflammation has led to the identification of markers that may also serve as new targets of therapy in the management of atherothrombotic disease. Inflammatory markers, such as C-reactive protein (CRP), have been shown to predict future cardiovascular events in individuals with and without established cardiovascular disease (CVD). Statins substantially reduce cardiovascular morbidity and mortality, and recently their anti-inflammatory properties have been investigated. In this paper, we discuss biomarkers implicated in the inflammatory process leading to atherothrombosis, including CRP, adiponectin, monocyte chemoattractant protein 1 (MCP-1), CD40 ligand and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), and the effect of statins on these markers and their potential relationship to cardiovascular events.
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ABSTRACT: It is not yet clear whether intestinal mucosal permeability changes with advancing age in humans. This question is of high importance for drug and nutrition approaches for older adults. Our main objective was to answer the question if small intestinal barrier integrity deteriorates with healthy aging. We conducted a cross-sectional study including the pooled data of 215 nonsmoking healthy adults (93 female/122 male), 84 of whom were aged between 60 and 82 years. After a 12-h fast, all participants ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 5 h afterwards and analyzed for test sugars. The permeability index (PI = lactulose/mannitol) was used to assess small intestinal permeability. Low-grade inflammation defined by high-sensitivity C-reactive protein ≥1 mL/L and kidney function (estimated glomerular filtration rate) were determined in the older age group. The PI was similar in older compared to younger adults (P = 0.887). However, the urinary recovery of lactulose and mannitol was lower in the older adults and this change was neither associated with urinary volume nor glomerular filtration rate. The PI was not significantly correlated with low-grade inflammation or presence of noninsulin-dependent type 2 diabetes. However, it significantly deteriorated in the copresence of both conditions compared to low-grade inflammation alone (P = 0.043) or type 2 diabetes alone (P = 0.015). Small intestinal mucosal barrier does not deteriorate with age per se. But low-grade inflammation coupled with minor disease challenges, such as type 2 diabetes, can compromise the small intestinal barrier.04/2014; 2(4). DOI:10.1002/phy2.281
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ABSTRACT: OBJECTIVE: A waist:height ratio (WHtR) higher than 0.5 has been proposed as a cutoff point for abdominal obesity in both sexes and at all ages. It is unknown if this cutoff point is appropriate for previously undernourished adolescents. We assessed the cutoff value of the WHtR associated with an increased metabolic risk in 178 black South African 14- to 18-y-old adolescents (69 boys, 109 girls). METHODS: We measured weight, height, waist circumference, fasting plasma glucose and insulin levels, serum high-sensitivity C-reactive protein, and blood pressure and calculated the WHtR and homeostasis model assessment of insulin resistance (HOMA-IR). Using receiver operating characteristics curve analyses, we assessed the WHtR with the highest sensitivity and specificity to discriminate adolescents with increased fasting plasma glucose, HOMA-IR, serum high-sensitivity C-reactive protein, and blood pressure from those with "normal" values. RESULTS: The WHtR cutoff points derived from the receiver operating characteristics curves ranged from 0.40 to 0.41, with best diagnostic value at 0.41. A WHtR of 0.40 had 80% sensitivity and 38.5% specificity to classify adolescents with fasting blood glucose level higher than 5.6 mmol/L (area under the curve [AUC] 0.57). A WHtR of 0.41 had 64% sensitivity and 58.5% specificity for a HOMA-IR higher than 3.4 (AUC 0.66), 55% sensitivity and 55.6% specificity for a high-sensitivity C-reactive protein level higher than 1 mg/L (AUC 0.57), and 64% sensitivity and 50.2% specificity for a blood pressure higher than the age-, sex-, and height-specific 90th percentiles (AUC 0.56). Adolescents with a WHtR higher than 0.41 had an odds ratio of 2.46 (95% confidence interval 0.96-6.30) for having a HOMA-IR higher than 3.4. CONCLUSION: The WHtR cutoff to indicate metabolic risk for black South African adolescents is 0.41, which is lower than the proposed international cutoff of 0.5. The WHtR can be used for screening adolescents with components of the metabolic syndrome in intervention programs.Nutrition 12/2012; 29(3). DOI:10.1016/j.nut.2012.08.009 · 3.05 Impact Factor
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ABSTRACT: The cardinal role of chronic inflammation in the development of atherosclerosis is increasingly being recognized. Estrogens may prevent the evolution of atherosclerosis by suppressing immune response. Furthermore, the conflicting reports on the cardiovascular effects of hormone therapy between observational and clinical trials have triggered interest on the effect of alternative therapies on the cardiovascular system. The aim of this study was to assess the effect of estrogen, estrogen-progestin, tibolone and raloxifene therapy on circulating markers of chemotaxis in healthy postmenopausal women. Eighty-eight postmenopausal women aged 44-62 years were randomly allocated to daily: (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation, normal T-cell expressed and secreted (RANTES) were measured at baseline and at 3 months. Endogenous testosterone and free androgen index (FAI) correlated negatively, while SHBG correlated positively with serum RANTES (testosterone: r=-0.27, p=0.033; FAI: r=-0.43, p=0.004: SHBG: r=0.34, p=0.026). Serum MCP-1 decreased significantly in the CEE group (baseline 125.3+/-51 pg/ml, 3 months 84.5+/-36.1 pg/ml, p=0.043), while no difference was detected between baseline and post-treatment levels in the other groups. Furthermore, a significant decrease in serum RANTES was observed at the end of 3 months only in the E2/NETA and the raloxifene group (E2/NETA baseline 8690.6+/-3880.0 pg/ml, 3 months 6894.0+/-1720.0 pg/ml, p=0.007; raloxifene baseline 9042.4+/-3765.6 pg/ml, 3 months 6718.1+/-2366.2 pg/ml, p=0.011). Endogenous androgens may suppress chemotactic response. Postmenopausal hormone therapy and raloxifene may inhibit the expression of chemoattractant molecules and thus attenuate inflammation. The relevance of these findings in terms of clinically established caridoprotection remains to be clarified.Atherosclerosis 08/2007; 193(1):142-50. DOI:10.1016/j.atherosclerosis.2006.05.045 · 3.97 Impact Factor