High plasma C-reactive protein (CRP) is related to low paraoxonase-I (PON-I) activity independently of high leptin and low adiponectin in type 2 diabetes mellitus

Objectives In type 2 diabetes mellitus, circulating C‐reactive protein (CRP) is increased, whereas the high density lipoprotein (HDL)‐associated, anti‐oxidative and anti‐inflammatory enzyme, paraoxonase‐I, is decreased. Both high CRP and low paraoxonase‐I activity may predict cardiovascular disease. It is unknown whether lower paraoxonase‐I activity contributes to higher CRP levels in diabetes. In type 2 diabetic and control subjects, we determined the relationship of CRP with paraoxonase‐I when taking account of plasma levels of pro‐ and anti‐inflammatory adipokines. Design and patients In 81 type 2 diabetic patients and 89 control subjects, plasma high‐sensitive CRP, serum paraoxonase‐I activity (arylesterase activity, assayed as the rate of hydrolysis of phenyl acetate into phenol), plasma leptin, adiponectin, resistin and lipids were determined. Results Body mass index (BMI), waist, insulin resistance, triglycerides, CRP, leptin and resistin levels were higher (P < 0·05 to P < 0·001), whereas HDL cholesterol, paraoxonase‐I activity and adiponectin levels were lower (P = 0·02 to P < 0·001) in diabetic compared to control subjects. Multiple linear regression analysis demonstrated that, after controlling for age and gender, CRP was inversely related to paraoxonase‐I activity (β = –0·15, P = 0·028) and adiponectin (β = –0·18, P = 0·009), and positively to leptin (β = 0·33, P < 0·001) and BMI (β = 0·22, P = 0·007), independently of the diabetic state (or of fasting glucose or HbA1c), insulin resistance and lipids (P > 0·20 for all). Conclusions low paraoxonase‐I activity is related to higher CRP, independently of adipokines, as well as of obesity and lipids. Low paraoxonase‐I activity in type 2 diabetes mellitus may contribute to increased cardiovascular risk via an effect on enhanced systemic low‐grade inflammation.     

Platelet activation, coagulation activation and C-reactive protein in simultaneous samples from the vascular access and peripheral veins of haemodialysis patients

Introduction: Most studies of haemodialysis (HD) patients compare venous blood samples from controls with samples from the vascular access (VA) of HD patients. We hypothesised that VA samples may be more prothrombotic compared with venous samples. Methods: Samples were taken simultaneously from the VA and the contralateral antecubital vein, from 26 patients immediately before HD. Platelet function was assessed by (1) flow cytometric measurement of P‐selectin expression and fibrinogen binding (±ADP) and 2)Ultegra rapid platelet function assay. Plasma soluble P‐selectin, von Willebrand factor antigen, high sensitivity C‐reactive Protein (hs‐CRP), thrombin‐antithrombin III complex and D‐dimer measured by ELISA. Results: Thrombin receptor activating peptide‐induced platelet aggregation (P < 0.001) and hs‐CRP (P < 0.001) were higher in VA compared with venous samples. Unstimulated platelet fibrinogen binding (P = 0.016) and ADP‐stimulated P‐selectin expression (P = 0.008) were lower in VA compared with venous samples. The significant difference in hsCRP persisted when patients taking and not taking antiplatelet therapy were analysed separately, but platelet activation remained significantly different only in the nonantiplatelet group. Conclusion: There are statistically significant differences between sampling sites, although samples from the VA do not appear to be more pro‐thrombotic. Future studies comparing HD patients with controls should ensure uniformity of sampling sites to prevent inaccurate conclusions being drawn.     

Serum C-reactive protein (CRP) and microalbuminuria in relation to fasting and 2-h postload plasma glucose in a Chinese population

Objective Serum C‐reactive protein (CRP) and microalbuminuria are predictors of cardiovascular disease. The association of these factors of cardiovascular risk with fasting and 2‐h postload plasma glucose in a group of Chinese subjects was investigated. Design This was a cross‐sectional cohort study. Subjects and methods In 1776 subjects randomly selected from the permanent residents of a community in the city of Shanghai, China, a simplified 75‐g oral glucose tolerance test (fasting and 2‐h postload blood sampling only) was performed, and serum CRP concentrations and urinary albumin : creatinine ratio were measured. Results Serum CRP concentration significantly increased from 1·62 mg/l in normoglycaemic subjects to 2·63 mg/l in subjects with impaired glucose regulation, and to 3·09 mg/l in newly diagnosed diabetic patients (P < 0·0001). The corresponding prevalence of microalbuminuria also increased from 4·3% to 6·6% and to 11·4% (P < 0·0001). Both before and after adjustment for confounders, fasting and 2‐h postload plasma glucose levels were significantly associated with serum CRP concentration and the risk of microalbuminuria (P < 0·003). However, the association for CRP tended to be more prominent with 2‐h postload plasma glucose than with fasting plasma glucose. Indeed, with adjustments applied, for 1 SD change in fasting and 2‐h postload plasma glucose concentration, serum CRP concentration increased by 14% and 18% (between the two regression coefficients, P = 0·01), respectively. With similar adjustments, for 1 SD change in fasting and 2‐h postload plasma glucose concentration, the odds of microalbuminuria increased by 28% and 32% (P = 0·28 for the difference between 28% and 32%), respectively. Conclusions Our finding suggests that in Chinese plasma glucose, especially 2‐h postload, is associated with biological markers of cardiovascular disease, such as serum CRP concentration and microalbuminuria.     

Gender differences in C‐reactive protein,interleukin‐1 receptor antagonist and adiponectin levels in the metabolic syndrome: a population‐based study

Aims We explored gender differences in the association of high‐sensitivity C‐reactive protein (hs‐CRP), interleukin‐1 receptor antagonist (IL‐1Ra) and adiponectin with the metabolic syndrome (MetS) defined by the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) criteria. Methods A population‐based study of 923 middle‐aged subjects in Pieksämäki, East Finland. Results The prevalence of the MetS according to the IDF and NCEP definitions was 38% and 34% in men (N = 405) and 34% and 27% in women (N = 497), respectively. hs‐CRP and IL‐1Ra levels were higher in subjects with the MetS compared with those without the MetS in both sexes (P < 0.001). The levels of hs‐CRP (P < 0.001) and IL‐1Ra (P = 0.0016 for NCEP criteria, P = 0.0028 for IDF criteria) were significantly higher in women with MetS than in men with MetS. In contrast, in subjects without MetS, no gender differences in the levels of hs‐CRP or IL‐1Ra were found. Conclusion Women with MetS, defined by the IDF or NCEP criteria, had higher levels of hs‐CRP and IL‐1Ra than did men with MetS. Thus, low‐grade inflammation may contribute to the high risk of cardiovascular disease in women with MetS.     

Red Cell Distribution Width for Assessment of Activity of Inflammatory Bowel Disease

Background Impaired iron absorption or increased loss of iron was found to correlate with disease activity and markers of inflammation in inflammatory bowel disease (IBD). Red cell distribution width (RDW) could be a reliable index of anisocytosis with the highest sensitivity to iron deficiency. Aim The importance of RDW in assessment of IBD disease activity is unknown. In this study, we aimed to determine if RDW could be useful in detecting active disease in patients with IBD. Materials and methods A total of 74 patients with ulcerative colitis (UC) and 22 patients with Crohn’s disease (CD) formed the study group with 20 age- and sex-matched healthy volunteers as the control group. CD activity index higher than 150 in patients with CD was considered to indicate active disease. Patients with moderate and severe disease according to the Truelove-Witts scale were accepted as having active UC. In addition to RDW, serum C-reactive protein (CRP) and fibrinogen levels, erythrocyte sedimentation rates (ESR), leukocyte, and platelet counts were measured. Results Fourteen (63.6%) of the patients with CD and 43 (58.1%) of the patients with UC had active disease. RDW, fibrinogen, CRP, ESR, and platelet counts were all significantly elevated in patients having active IBD compared with those without active disease and controls (P < 0.05). The study subjects were further classified into two subgroups: cases with active and inactive UC and those with active and inactive CD. A subgroup analysis indicated that for an RDW cutoff of 14, the sensitivity for detecting active UC was 88% and the specificity was 71% (area under curve [AUC] 0.81, P = 0.0001). RDW was the most sensitive and specific parameter indicating active UC. However, the same was not true for CD since CRP at a cutoff of 0.54 mg/dl showed a sensitivity of 92% and a specificity of 63% (AUC 0.92, P = 0.001), whereas RDW at a cutoff of 14.1 showed 78% sensitivity and 63% specificity to detect active CD. Conclusion Among the laboratory tests investigated, including fibrinogen, CRP, ESR, and platelet counts, receiver operating characteristic (ROC) curve analysis indicated RDW to be the most significant indicator of active UC. For CD, CRP was an important marker of active disease.     

Concentrations of the acute phase reactants high-sensitive C-reactive protein and YKL-40 and of interleukin-6 before and after treatment in patients with acromegaly and growth hormone deficiency

Background Acromegaly is accompanied by increased cardiovascular mortality and a cluster of proatherogenic risk factors. In the general population, ischaemic heart disease (IHD) is associated with elevated levels of inflammatory markers. The acute phase reactant (APR) C‐reactive protein (CRP) has been reported to be reduced in acromegaly and increase after treatment, suggesting that excess of GH/IGF‐I could have anti‐inflammatory effects. This is in accordance with results obtained in patients with growth hormone deficiency (GHD), where increased levels of CRP have been reported. Objective To investigate the hypothesis that the GH/IGF‐I system is a suppressive regulator of inflammatory processes. Subjects and methods Twenty‐one acromegalic patients and 19 GH‐deficient patients were studied. The two APRs CRP and YKL‐40 and the proinflammatory cytokine interleukin‐6 (IL‐6) were measured before and after treatment and in healthy matched controls. Results In acromegalic patients, serum concentrations of high‐sensitive CRP (hsCRP) and YKL‐40 were reduced compared to controls (P < 0·001) and increased (P < 0·001) after treatment, together with IL‐6 (P = 0·021), to levels comparable with controls. Pretreatment serum YKL‐40 and IL‐6 showed a significant inverse correlation with IGF‐I and GH. In GH‐deficient patients, hsCRP and YKL‐40 were elevated compared to controls (P = 0·001 and P = 0·048). During treatment, levels of both APRs showed a trend towards a decrease (P = 0·087 and P = 0·060), and after treatment, levels of YKL‐40 no longer differed from that of controls. Serum IL‐6 was not different from controls and did not change during GH treatment. Conclusion The results point to the possibility of a relationship between GH disturbances and inflammatory processes.     

Clinical predictors of high posttreatment platelet reactivity to clopidogrel in Koreans

Introduction: High posttreatment platelet reactivity to clopidogrel (HPPR) is associated with major adverse cardiac events. However, the clinical predictors of HPPR in Asians have not been studied previously. Aims: We sought to determine clinical predictors of HPPR in Koreans. Results: We measured platelet reactivity with the VerifyNow P2Y12 assay in 1431 consecutive patients undergoing coronary angiography. We used the cut‐off value of greater than 275 P2Y12 Reaction Unit (PRU) to define patients with HPPR. The clinical characteristics were compared between patients with HPPR (36.3%) and those without HPPR (63.7%). The mean age (65.4 ± 9.1 vs. 62.2 ± 9.7 years) was higher, hypertension (68.5% vs. 62.0%), diabetes mellitus (35.4% vs. 28.5%), chronic kidney disease (36.3% vs. 22.5%), renal replacement treatment (1.2% vs. 0.2%), and congestive heart failure (1.3% vs. 0.3%) were more common among patients with HPPR, while male gender (72.6% vs. 54.8%) and smoking (19.9% vs. 13.1%) were more common among non‐HPPR patients. Mean glomerular filtration rate (63.5 ± 18.6 vs. 69.7 ± 16.1 mL/min/1.73 m³) was lower and C‐reactive protein (hs‐CRP) (6.6 ± 20.5 mg/L vs. 4.2 ± 12.1 mg/L) level was higher among those with HPPR. Independent predictors of HPPR were female gender (OR 1.90, P≤ 0.001), chronic kidney disease (OR 1.51, 0 = 0.004), diabetes mellitus (OR 1.35, P= 0.024), hs‐CRP ≥ 2.0 mg/L (OR 1.31, P= 0.005), and age increase in decades (OR 1.21, P= 0.002), while smoking was negative risk factor (OR 0.63, P= 0.015). The number of risk factors was linearly associated with the risk of HPPR, with most patients having one or two predictors. Conclusion: In Korean population, independent clinical predictors of HPPR included diabetes mellitus, increased age, female gender, chronic kidney disease, and hs‐CRP ≥ 2.0 mg/L, while cigarette smoking was associated with better responsiveness. Mean platelet reactivity and HPPR prevalence steadily increased with the number of clinical predictors.     

Novel Inflammatory Marker in Dialysis Patients: YKL‐40

YKL‐40 has been introduced as a marker of inflammation in different clinical situations. The association between YKL‐40 and inflammation in chronic renal failure patients has not been researched currently. The objectives of this study were to establish serum YKL‐40 concentrations in dialysis patients with chronic renal failure compared to healthy subjects and to explore its relationships with a proinflammatory cytokine, interleukine‐6 (IL‐6) and an acute phase mediator, high sensitivity C‐reactive protein (hs‐CRP). The study population included hemodialysis patients (N = 43; mean age of 40.9 ± 14.5), peritoneal dialysis patients (N = 38; mean age of 45.8 ± 13.7) and healthy subjects (N = 37; mean age of 45.5 ± 10.6). Serum concentrations of YKL‐40, IL‐6, hs‐CRP and routine laboratory measures were evaluated. Compared to the healthy subjects, hemodialysis and peritoneal dialysis patients had higher concentrations of YKL‐40, IL‐6, hs‐CRP, as well as lower concentrations of hemoglobin, serum albumin and high density lipoprotein‐cholesterol (P < 0.001). YKL‐40 concentrations were positively correlated with serum creatinine (P < 0.001, r = 0.495), IL‐6 (P < 0.001, r = 0.306), hs‐CRP (P = 0.001, r = 0.306) levels and inversely correlated with hemoglobin (P = 0.002, r = ?0.285), serum albumin (P < 0.001, r = ?0.355) and high density lipoprotein‐cholesterol (P = 0.001, r = ?0.306). In multivariate regression analysis YKL‐40 was associated with creatinine, serum albumin and hs‐CRP concentrations after adjustments with covariates. Dialysis patients with chronic renal failure have elevated serum YKL‐40 concentrations. Associations with standard inflammatory parameters suggest that YKL‐40 might be a novel inflammatory marker in this population.     

Apolipoprotein B/A-I and total cholesterol/high-density lipoprotein cholesterol ratios both predict cardiovascular events in the general population independently of nonlipid risk factors, albuminuria and C-reactive protein

Kappelle PJWH, Gansevoort RT, Hillege JL, Wolffenbuttel BHR, Dullaart RPF on behalf of the PREVEND study group (University Medical Center Groningen and University of Groningen, Groningen, The Netherlands). Apolipoprotein B/A‐I and total cholesterol/high‐density lipoprotein cholesterol ratios both predict cardiovascular events in the general population independently of nonlipid risk factors, albuminuria and C‐reactive protein. J Intern Med 2011; 269 : 232–242. Abstract. Background. The total cholesterol/high‐density lipoprotein cholesterol (TC/HDL‐C) and apolipoprotein (apo) B/A‐I ratios predict major adverse cardiovascular events (MACEs). The extent to which these associations are modified by high‐sensitivity C‐reactive protein (hs‐CRP) and albuminuria is largely unknown. We compared the strength of these ratios with first MACE in the general population and determined whether these associations remain when taking account of these risk markers. Subjects and methods. A prospective case–cohort study was performed among 6948 subjects (PREVEND cohort) without previous cardiovascular disease and who did not use lipid‐lowering drugs initially. Fasting serum TC, low‐density lipoprotein cholesterol (LDL‐C), HDL‐C, non‐HDL‐C, apoB, apoA‐I, triglycerides, hs‐CRP and albuminuria were measured at baseline. The composite endpoint was incident MACE. Results. A total of 362 first cardiovascular events occurred during 7.9 years of follow‐up. All pro‐ and anti‐atherogenic measures of lipoproteins and apos predicted MACEs in age‐ and sex‐adjusted Cox proportional hazard analyses (P = 0.018 to P < 0.001). The age‐ and sex‐adjusted hazard ratio (HR) was 1.37 [95% confidence interval (CI), 1.26–1.48] for the apoB/apoA‐I ratio and 1.24 (95% CI, 1.18–1.29) for the TC/HDL‐C ratio (both P < 0.001). These relationships were essentially unaltered after additional adjustment for triglyceride levels. Pair‐wise comparison revealed that these ratios were of similar importance in age‐ and sex‐adjusted analysis (P = 0.397). The HRs of apoB/apoA‐I (P < 0.001) and TC/HDL‐C (P < 0.001) for risk of MACEs were only marginally attenuated by additional controlling for traditional risk factors (hypertension, diabetes, obesity and smoking), hs‐CRP and albuminuria. Conclusions. First MACE is associated with both the fasting serum apoB/apoA‐I ratio and the TC/HDL‐C ratio in the general population, independently of triglycerides, hs‐CRP and albuminuria.     

Correlation of Serum-Soluble Triggering Receptor Expressed on Myeloid Cells-1 with Clinical Disease Activity in Inflammatory Bowel Disease

Although triggering receptor expressed on myeloid cells-1 (TREM-1) has recently been shown to be upregulated in the intestines of patients with inflammatory bowel disease (IBD), it remains unclear whether serum-soluble TREM-1 (sTREM-1) level reflects disease activity in patients with IBD. This study aimed to evaluate the correlation of sTREM-1 level with disease activity in IBD. We prospectively enrolled consecutive patients with IBD and assessed their clinical disease activity using the guidelines of the American College of Gastroenterology. At the time that disease activity was assessed, sTREM-1 level (using an enzyme-linked immunosorbent assay method) and other laboratory findings including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured. A total of 31 patients with ulcerative colitis (UC) and 22 with Crohn’s disease (CD) were enrolled. The mean sTREM-1 level in patients with either UC (60.4 ± 41.8 pg/ml) or CD (66.5 ± 42.4 pg/ml) was significantly higher than in healthy controls (0.6 ± 1.4 pg/ml) (P = 0.003 and P = 0.002, respectively). In patients with UC, sTREM-1 level was more highly correlated with disease activity (r = 0.849) than was ESR (r = 0.619) or CRP level(r = 0.546). Moreover, sTREM-1 level correlated well with disease activity irrespective of disease extent. In patients with CD, sTREM-1 level was lower in those with remission compared with those without (46.8 ± 35.3 pg/ml versus 77.8 ± 43.1 pg/ml), but this trend did not reach statistical significance (P = 0.100). The results of our study suggest that sTREM-1 could be a potential marker for disease activity in IBD patients, especially those with UC. An erratum to this article can be found at     

Exercise training improves autonomic function and inflammatory pattern in women with polycystic ovary syndrome (PCOS)

Background Polycystic ovary syndrome (PCOS) is a common female reproductive‐age endocrine disease predominantly characterized by chronic anovulation, hyperandrogenism, insulin‐resistance and low‐grade inflammatory status. Exercise training (ET) favourably modulates cardiopulmonary function and insulin‐sensitivity markers in PCOS women. The present study investigated the effects of ET on autonomic function and inflammatory pattern in PCOS women. Study design Prospective baseline uncontrolled clinical study. Methods One‐hundred and eighty five PCOS women referred to our department were screened for the inclusion into the study protocol from March 2004 to July 2007. One‐hundred and twenty four PCOS women met the criteria for the inclusion into the study protocol and were subdivided into two groups each composed of 62 patients: PCOS‐T (trained) group underwent 3‐month ET program, whereas PCOS‐UnT (untrained) group did not. At baseline and at 3‐month follow‐up, hormonal and metabolic profile, cardiopulmonary parameters, autonomic function (as expressed by heart rate recovery, HRR) and inflammatory pattern [as expressed by C‐reactive protein (CRP) and white blood cells (WBCs) count] were evaluated. Results PCOS‐T showed a significant (P < 0·05) improvement in maximal oxygen consumption (VO_2max) and in post‐exercise HRR, and a significant (P < 0·001) decrease in CRP and WBCs; whereas no statistically significant changes of the same parameters were observed in PCOS‐UnT. Multiple linear regression analysis showed that 3‐month HRR is linearly related to the inclusion in training group (β = 0·316, P < 0·001), VO_2max (β = 0·151, P = 0·032) and the ratio between glucose and insulin area under curve (AUC) (β = 0·207, P = 0·003), and inversely related to body mass index (β = –0·146, P = 0·046), insulin AUC (β = –0·152, P = 0·032), CRP (β = –0·165, P < 0·021), and WBCs count (β = –0·175, P = 0·039). Conclusions Exercise training improves autonomic function and inflammatory pattern in PCOS women.     

Impact of preprocedural high-sensitivity C-reactive protein levels on uncovered stent struts: an optical coherence tomography study after drug-eluting stent implantation

Background

There are no sufficient data to evaluate the relationship between high‐sensitivity C‐reactive protein (hs‐CRP) and uncovered stent struts on optical coherence tomography (OCT) after drug‐eluting stent (DES) implantation.

Hypothesis

We evaluated the relationship between the preprocedural level of hs‐CRP and incomplete neointimal coverage of DES struts on OCT.

Methods

This study was conducted using 124 eligible patients (132 lesions) treated with sirolimus‐eluting stents (SES) or zotarolimus‐eluting stents (ZES). The subjects were divided into 2 groups based on the preprocedural hs‐CRP level: high‐CRP (≥3 mg/L; 58 lesions) and normal‐CRP (<3 mg/L, 74 lesions) groups. The percentage of uncovered struts, calculated as the ratio of uncovered struts to total struts in all OCT cross‐sections, was compared between the 2 groups according to initial clinical presentation (stable angina [SA] vs acute coronary syndrome) and the type of implanted DES (SES vs ZES).

Results

There was no significant correlation between hs‐CRP and the percentage of uncovered struts on OCT in all enrolled lesions. In the SA subgroup, the percentage of uncovered struts was significantly higher in the high‐CRP group than in the normal‐CRP group (8.1 ± 11.6% vs 3.8 ± 7.9%, P = 0.018). There was significant correlation between hs‐CRP level and the percentage of uncovered struts in SA patients with SES (r = 0.280, P = 0.039), but not ZES (r = ? 0.063, P = 0.729).

Conclusions

Preprocedural hs‐CRP level could affect incomplete neointimal coverage of struts after DES implantation depending on the initial clinical presentation and the type of implanted DES. Copyright © 2011 Wiley Periodicals, Inc. This study was partly supported by grants from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (No. A085012 and A102064), the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (No. A085136), and the Cardiovascular Research Center, Seoul, Korea. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

     

Association of cytotoxic T lymphocyte associated antigen-4 gene (rs60872763) polymorphism with Crohn's disease and high levels of serum sCTLA-4 in Crohn's disease

Background and Aim: Our aim was to evaluate cytotoxic T lymphocyte associated antigen‐4 (CTLA‐4) gene polymorphisms in Crohn's disease (CD) and explore soluble CTLA‐4 (sCTLA‐4) levels in serum of CD patients in central China. Methods: A total of 126 Chinese CD patients and 300 healthy controls were enrolled in this study. CTLA‐4 (AT)n repeat polymorphism was genotyped by a semiautomatic fluorescently labeled polymerase chain reaction (PCR) method, and CTLA‐4 ‐1661A/G and ‐1722T/C polymorphisms were genotyped by DNA sequencing. Serum sCTLA‐4 and C‐reactive protein (CRP) levels were determined by enzyme linked immunosorbent assay (ELISA) and immunonephelometry, respectively. Results: The frequency of 84 bp allele of CTLA‐4 (AT)n repeats was lower in CD patients than in the healthy controls (22.2% vs 33.2%, P = 0.001, odds ratio = 0.58, 95% confidence interval: 0.41–0.81). The 84 bp allele carriers of (AT)n repeats were associated with non‐stricturing and non‐penetrating disease behavior in CD patients (P = 0.007). Serum sCTLA‐4 levels were more elevated in CD patients than in the healthy controls (P < 0.001). Among CD patients, serum sCTLA‐4 levels were increased in active disease compared with inactive disease (P = 0.015), and were correlated with CRP levels (r = 0.524, P < 0.001). Serum sCTLA‐4 levels were higher in CD patients with stricturing disease behavior than in patients with other disease behaviors (P = 0.009). Conclusions: 84 bp allele of CTLA‐4 (AT)n repeat polymorphism was associated with CD in central China. sCTLA‐4 levels were highly expressed in CD, especially in active disease, and were correlated with CRP levels and disease behavior in CD patients.     

Comparison of clinical characteristics and management of inflammatory bowel disease in Hong Kong versus Melbourne

Background and Aim: Inflammatory bowel disease (IBD), common in Melbourne, was rare but is now increasing in incidence in Hong Kong (HK). To investigate whether these are the same diseases in the West and East, potential causes of changing incidence, and to plan resource needs, an appreciation of clinical characteristics in contrasting populations is essential. Methods: Disease characteristics were collected from prospectively populated IBD databases in two specialist centers in Melbourne, Australia and HK. Results: Of 795 patients (Crohn's disease [CD] : ulcerative colitis [UC] Melbourne 272:159 and HK 161:203), the age of diagnosis was higher, there were proportionally more male patients with CD but no UC sex difference, fewer patients were current or ex‐smokers (CD 8% vs 50%; UC 17% vs 35%) and a family history of IBD was less common (2% vs 11%; P < 0.001) in HK compared to Melbourne. Stricturing and perianal CD were more common in HK (12% vs 6%; P < 0.001; and 29% vs 16%; P = 0.001, respectively). In HK for UC, more patients had extensive disease at diagnosis (42% vs 22%) but colectomy was less common (7% vs 20%; P < 0.001). In Melbourne there was greater steroid use at diagnosis and patients were more likely to receive an immunomodulator or anti‐tumor necrosis factor agent. Conclusions: IBD in HK was diagnosed at an older age, and had more complicated disease behavior than in Melbourne. Medical therapy, however, was less intense in HK. These differences may relate to real differences in disease or delayed diagnosis due to late presentation and less disease recognition in HK.     

Reduction in C‐reactive protein indicates successful targeting of the IL‐1/IL‐6 axis resulting in improved survival in early stage multiple myeloma

We report the long‐term follow‐up results of a phase II trial of IL‐1 receptor antagonist and low‐dose dexamethasone for early stage multiple myeloma (MM). Patients were eligible if they had smoldering multiple myeloma (SMM) or indolent multiple myeloma (IMM) without the need for immediate therapy. Forty seven patients were enrolled and subsequently treated with IL‐1Ra; in 25/47 low‐dose dexamethasone (20 mg weekly) was added. The primary endpoint was progression‐free survival (PFS). In the clinical trial, three patients achieved a minor response (MR) to IL‐1Ra alone; five patients a partial response (PR) and four patients an MR after addition of dexamethasone. Seven patients showed a decrease in the plasma cell labeling index (PCLI) which paralleled a decrease in the high sensitivity C‐reactive protein (hs‐CRP). The median PFS for the 47 patients was 1116 days (37.2 months). The median PFS for patients without (n = 22) and with (n = 25) a decrease in their baseline hs‐CRP was 326 days (11 months) vs. 3139 days (104 months) respectively (P <0.0001). The median overall survival (OS) for the 47 patients was 3482 days (9.5 years). The median OS for patients without and with a decrease in their baseline hs‐CRP was 2885 days (7.9 years) vs. median not reached, respectively (P = 0.001). In SMM/IMM patients at risk for progression to active myeloma, reduction in the hs‐CRP indicates successful targeting of the IL‐1/IL‐6 axis resulting in improved PFS and OS. (Clinical Trials.gov Identifier: NCT00635154) Am. J. Hematol. 91:571–574, 2016. © 2016 Wiley Periodicals, Inc.     

Low serum level of high‐sensitivity C‐reactive protein in a Japanese patient with maturity‐onset diabetes of the young type 3 (MODY3)

High‐sensitivity C‐reactive protein (hs‐CRP) levels in European populations are lower in patients with maturity‐onset diabetes of the young type 3 (MODY3) than in those with type 2 diabetes. hs‐CRP levels have been suggested to be useful for discriminating MODY3 from type 2 diabetes. As hs‐CRP levels are influenced by various factors including race and body mass index, it is worthwhile to examine whether hs‐CRP can serve as a biomarker for MODY3 in Japanese. Here we describe the case of a Japanese MODY3 patient with a nonsense mutation in the HNF1A gene. Two measurements showed consistently lower hs‐CRP levels (<0.05 and 0.09 mg/L) than in Japanese patients with type 1 and type 2 diabetes. Hepatic expression of Crp messenger ribonucleic acid was significantly decreased in Hnf1a knockout mice. The hs‐CRP level might be a useful biomarker for MODY3 in both Japanese and European populations.     

Correlated expression of high-sensitivity C-reactive protein in relation to disease activity in inflammatory bowel disease: lack of differences between Crohn's disease and ulcerative colitis

BACKGROUND/AIMS: As opposed to regular C-reactive protein (CRP) assays, the introduction of high-sensitivity ones has enabled us to detect low grade inflammation in patients with inflammatory bowel disease (IBD). We addressed the subject of the degree of correlation between the concentration of high-sensitivity CRP (hs-CRP) and the inflammatory IBD activity score. METHODS: Included were 90 patients with Crohn's disease (CD), 70 with ulcerative colitis (UC) and 160 controls. Disease activity was determined using CD activity index (CDAI) for CD and Mayo score for UC. The Dade Boering BNII Nephelometer was used to determine the hs-CRP concentrations. RESULTS: The coefficient of correlation between hs-CRP and the disease activity score was similar for both UC (0.26) and CD (0.36). CONCLUSIONS: These findings are relevant for therapeutic intervention in which a greater absolute reduction in the hs-CRP concentration in CD patients (who generally present higher CRP concentrations than those found in UC) might be interpreted as a better response compared to the same absolute reduction in UC patients. This information is needed for clinicians using the hs-CRP assay to estimate IBD disease activity in daily practice.     

Prevalence and predictors of elevated high‐sensitivity C‐reactive protein in post–myocardial infarction patients: Insights from the VIRGO and TRIUMPH registries

Elevated high‐sensitivity C‐reactive protein (hs‐CRP) is associated with worse cardiovascular outcomes in patients with acute myocardial infarction (AMI), but little is known about the distribution of hs‐CRP levels and predictors of elevated hs‐CRP after AMI in the real world. Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) and Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) are prospective AMI registries in the United States that assessed hs‐CRP levels 30 days after AMI. TRIUMPH additionally assessed hs‐CRP levels at the time of AMI and at 6 months. Hierarchical models were built to examine predictors of elevated hs‐CRP (≥2.0 mg/L) at 30 days in both registries and at 6 months after AMI in TRIUMPH. Of 3410 patients in both registries, 58.6% had elevated hs‐CRP 30 days after AMI. Patients with elevated hs‐CRP at 30 days were more likely to be older, female, obese, smokers, report financial difficulties, and have higher low‐density lipoprotein cholesterol levels on admission, diabetes, and hypertension. In TRIUMPH, baseline hs‐CRP ≥2 mg/L (n = 1301) was significantly associated with elevated hs‐CRP at follow‐up (P < 0.001). Similar associations were found in TRIUMPH patients with elevated hs‐CRP at 6 months. Our study identified a high prevalence and several patient characteristics associated with elevated hs‐CRP at 1 and 6 months after discharge. Further studies to test routine screening after AMI may be warranted to identify higher‐risk patients for more aggressive secondary prevention.     

Accuracy of the highly sensitive C-reactive protein/albumin ratio to determine disease activity in inflammatory bowel disease

Persistent disease activity is associated with a poor prognosis in patients with inflammatory bowel disease (IBD). This study aims to explore the accuracy of the highly sensitive C-reactive protein/albumin ratio (CAR) in determining IBD activity.The clinical data of 231 IBD patients treated at Peking Union Medical College Hospital from 2012 to 2018 were analyzed retrospectively. The patients were classified as having active disease or remission according to the Crohn disease activity index scores for patients with Crohn disease (CD) and partial Mayo scores for patients with ulcerative colitis (UC).This study included 231 IBD patients (137 CD and 94 UC). From these groups, 182 patients had active disease, while 49 patients were in remission. The platelet counts, erythrocyte sedimentation rates, high-sensitivity C-reactive protein levels, and CAR scores were significantly higher, while hemoglobin levels, ALB, and body mass indexes were significantly lower in patients with active disease (P < 0.01). The hsCRP, CAR, and ALB significantly correlated with disease activity for both CD and UC (P < 0.001). The area under the curve (AUC) of CAR was highest among the laboratory indexes at 0.829, and the AUC of CAR in the UC patients was larger than that of the CD patients. Also, CAR with cutoff value of 0.06 displayed the highest sensitivity among the indexes for IBD activity at 83.05%.CAR is a useful biomarker for identifying disease activity in patients with CD and UC. Higher CAR levels are indicative of increased IBD activity. CAR may be more valuable in UC than that in CD for assessing the degree of IBD activity.     

Severity of periodontal disease correlates to inflammatory systemic status and independently predicts the presence and angiographic extent of stable coronary artery disease

Background. Periodontal disease (PD) has been recognized as a risk factor for systemic diseases, but its involvement in the pathogenesis of coronary artery disease (CAD) remains debated. Objectives. We sought to evaluate the potential relations between severity of the PD, inflammatory response and angiographic lesions extent in patients with stable CAD. Design. A total of 131 subjects referred to our centre for coronary angiography were evaluated for presence and extension of CAD, then divided into two groups, one with presence of lesions (cases, n = 85) and other one with absence of lesions (controls, n = 46). Mean periodontal pocket depth (PPkD), high sensitivity C reactive protein (hs‐CRP), serum amyloid A protein (SAA) and fibrinogen levels were measured in all patients. Results. Cases and controls did not differ according to their baseline characteristics and prevalence of traditional cardiovascular risk factors. PPkD was greater in patients with CAD than in controls (2.24 ± 1.28 mm vs 1.50 ± 0.93 mm, P < 0.001 by Student’s t‐test). Systemic inflammatory response was more pronounced in cases than in controls, with higher values of hs‐CRP, SAA and fibrinogen. Furthermore, PPkD values correlated with hs‐CRP (r = 0.80, P < 0.001), SAA (r = 0.71, P < 0.001), fibrinogen levels (r = 0.72, P < 0.001) and the American College of Cardiology/American Heart Association angiographic score (r = 0.68, P < 0.001) in cases. Multivariate analysis indicated a persistent independent correlation between PPkD and angiographic score after adjustment for inflammatory markers levels. Conclusion. In the present study, PD lesions predicted presence of CAD stenosis in patients with cardiovascular risk factors. PD severity was correlated to angiographic extent of coronary lesions, independent of systemic inflammatory status. Those results suggest that these patients might benefit from an intensive periodontal therapy to prevent CAD progression.