C-reactive protein as a risk factor versus risk marker

PURPOSE OF REVIEW: C-reactive protein (CRP) is consistently associated with cardiovascular disease in prospective and cross-sectional clinical and epidemiological studies. Inflammation is an important mechanism in cardiovascular disease, and the plasma level of CRP is considered to reflect the inflammatory condition of the patient and/or the vessel wall. In addition, there are also a number of indications for a causal role of CRP in cardiovascular disease. RECENT FINDINGS: A number of new publications show potential causal effects of CRP on cardiovascular disease, and evidence from human-CRP transgenic animals also indicates a causal contribution of CRP to cardiovascular disease. On the other hand, a new large prospective study and an updated meta-analysis indicate that the contribution of CRP to cardiovascular disease is less impressive than reported earlier (odds ratio, 1.58; 95% confidence interval, 1.48-1.68). SUMMARY: We review here the most recent evidence on mechanisms by which CRP is involved as a causal factor in the precipitation of cardiovascular disease. Evidence for such a role is accumulating.     

Gender and the active smoking and high-sensitivity C-reactive protein relation in late adolescence

C-reactive protein (CRP), smoking, and oral contraceptive (OC) use are associated with CVD risk in adults. This study examines the effect of smoking on high-sensitivity CRP (hs-CRP) levels, and the interactive effects of sex and OC use on this relationship in an adolescent cohort. A total of 1,050 adolescents (mean age 17 ± 0.25 years) from the Western Australian Pregnancy Cohort (Raine) Study had anthropometric, lifestyle, and metabolic measures recorded. The association between smoking status and log-transformed hs-CRP was analyzed using multivariable Tobit linear regression models, with adjustment for adiposity, lifestyle, and early-life confounders. A three-level variable (girls not using OCs, girls using OCs, and boys) was employed to assess the interactive effects of sex, OC use, and smoking. Smoking associated with higher hs-CRP levels in girls not using OCs (b = 0.571; P = 0.001), but not in girls using OCs (b = −0.117; P = 0.598) or in boys (b = 0.183; P = 0.2). OC use in nonsmoking girls was the strongest factor associated with higher hs-CRP levels (b = 1.189; P < 0.001). This study has demonstrated a more robust effect of smoking on hs-CRP levels in girls not using OCs compared with boys. The findings may explain why CVD risk conferred by smoking is higher in women than in men.     

儿童慢性牙周炎与口腔幽门螺杆菌感染的相关性

目的 探讨慢性牙周炎患儿与其口腔中幽门螺杆菌(Helicobacter pylori, H. pylori)的相关性,为儿童慢性牙周炎的临床治疗提供指导。 方法 分别随机选取2017年5月-2019年5月来我院口腔科就诊的慢性牙周炎患儿和牙周健康的儿童作为观察组(92例)和对照组(92例)。应用PCR技术检测采集的牙菌斑和含漱液样品中的H. pylori,并比较两组儿童口腔H. pylori检出率的差异及龈上、龈下菌斑中的分布情况以及不同程度牙周炎患儿检出率的差异。 结果 观察组患儿口腔中H. pylori的检出率明显高于对照组,两组之间差异有统计学意义(χ2=9.588 1,P2= 58.119 9,P2=19.783 1,P结论 口腔中H. pylori可能在儿童慢性牙周炎致病过程具有一定的促进作用,二者具有相关性。     

Potential sensitivity of hepatic specific protein regucalcin as a marker of chronic liver injury

A novel calcium-binding protein regucalcin has been shown to be specifically expressed in the liver of various specifies including human. Regucalcin concentration in the serum of patients with chronic liver injury was estimated by enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG. Serum samples were obtained from 42 persons who were diagnosed as liver disorder. Serum regucalcin concentration in all patients was in the range of 3.7-69.6 ng/ml, although regucalcin was not entirely seen in the serum of normal subjects (10 persons) without hepatitis. Meanwhile, in 18 patients with liver injury, serum glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) activities were normal value (less than 40 I.U./l). Serum GOT and GPT activities from 24 patients showed a comparatively higher level (50-234 I.U./l). The present results demonstrate the potential sensitivity of regucalcin as a marker of chronic liver injury. (Mol Cell Biochem 167: 187-190, 1997)     

Salivary and serum procalcitonin and C-reactive protein as biomarkers of periodontitis in United States veterans with osteoarthritis or rheumatoid arthritis

Serum procalcitonin (ProCT) is elevated in response to bacterial infections, whereas high sensitivity C-reactive protein (hsCRP) is a nonspecific inflammatory marker that is increased by excess adipose tissue. We examined the efficacy of ProCT and hsCRP as biomarkers of periodontitis in the saliva and serum of patients with arthritis, which is characterized by variable levels of systemic inflammation that potentially can confound the interpretation of inflammatory biomarkers. Blood and unstimulated whole saliva were collected from 33 patients with rheumatoid arthritis (RA) and 50 with osteoarthritis (OA). Periodontal status was assessed by full mouth examination and patients were categorized as having no/mild, moderate or severe periodontitis by standard parameters. Salivary and serum ProCT and hsCRP concentrations were compared. BMI, diabetes, anti-inflammatory medications and smoking status were ascertained from the patient records. Differences between OA and RA in proportionate numbers of patients were compared for race, gender, diabetes, adiposity and smoking status. Serum ProCT was significantly higher in arthritis patients with moderate to severe and severe periodontitis compared with no/mild periodontitis patients. There were no significant differences in salivary ProCT or salivary or serum hsCRP in RA patients related to periodontitis category. Most of the OA and RA patients were middle aged or older, 28.9% were diabetic, 78.3% were overweight or obese, and slightly more than half were either current or past smokers. The OA and RA groups differed by race, but not gender; blacks and males were predominant in both groups. The OA and RA groups did not differ in terms of controlled or uncontrolled diabetes, smoking status or BMI. The RA patients had been prescribed more anti-inflammatory medication than the OA patients. Our results demonstrate that circulating ProCT is a more discriminative biomarker for periodontitis than serum hsCRP in patients with underlying arthritis. Any elevation in salivary and serum hsCRP due to periodontitis apparently was overshadowed by differences among these patients in factors that influence CRP, such as the extent of inflammation between RA and OA, the extent of adipose tissue, the use of anti- inflammatory medications and smoking status. Although our study showed no differences in salivary ProCT related to severity of periodontitis, this biomarker also may be useful with further refinement.     

Role of resistin as a marker of inflammation in systemic lupus erythematosus

Introduction

Resistin is a cystein-rich secretory adipokine. It is proposed to have proinflammatory properties in humans. The aim of this study was to determine associations between serum levels of resistin and markers of inflammation and bone mineral density (BMD) in female patients with systemic lupus erythematosus (SLE).

Methods

One hundred sixty-three female patients with SLE (20 to 82 years old) were examined in a cross-sectional study. Venous blood samples were analyzed for resistin, erythrocyte sedimentation rate (ESR), C-reactive protein, creatinine, fasting lipids, complements, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, sIL-6R (soluble IL-6 receptor), ICTP (C-terminal telopeptide of type I collagen), and PINP (N-terminal propeptide of type I procollagen). Simple and multiple regression analyses as well as logistic regression analyses were performed. Resistin in serum was compared with 42 healthy female controls with respect to age.

Results

Serum resistin levels in controls were similar to those of patients with SLE. Markers of inflammation and current dose of glucocorticosteroids correlated positively to resistin in serum. Markers of renal function, number of prevalent vertebral fractures, and BMD were also significantly associated with resistin. In a multiple regression model, ESR, creatinine, C3, current glucocorticosteroid dose, high-density lipoprotein, and BMD radius remained significantly associated with resistin. In logistic regression analyses with resistin as the independent variable, a significant association was found with ESR (normal or elevated) but not with S-creatinine or z score for hip and radius total.

Conclusion

Although resistin measurements did not differ between patients and controls, resistin was clearly associated with general inflammation, renal disease, treatment with glucocorticosteroids, and bone loss. We hypothesize that resistin has proinflammatory and disease-promoting properties in SLE. Further studies are needed to elucidate the mechanism behind these associations.     

Oxidative stress, chronic inflammation, and telomere length in patients with periodontitis

The aim of this study was to determine leukocyte telomere length (LTL) in individuals with periodontitis and controls, exploring its relationship with systemic inflammation and oxidative stress. Five hundred sixty-three participants were recruited for this case-control study: 356 subjects with and 207 subjects without periodontitis. LTL was measured by a qPCR technique from leukocytes' DNA. Global measures of oxidative stress (reactive oxygen metabolites) and biological antioxidant potential in plasma were performed together with high-sensitivity assays for C-reactive protein (CRP). Leukocyte counts and lipid profiles were performed using standard biochemistry. Cases had higher levels of CRP (2.1±3.7mg/L vs 1.3±5.4mg/L, P<0.001) and reactive oxygen metabolites (378.1±121.1 U Carr vs 277.4±108.6 U Carr, P<0.001) compared to controls. Overall, cases had shorter LTL with respect to controls (1.23±0.42 vs 1.12±0.31T/S ratio, P=0.006), independent of age, gender, ethnicity, and smoking habit. When divided by subgroup of periodontal diagnosis (chronic, n=285; aggressive, n=71), only chronic cases displayed shorter LTL (P=0.01). LTL was negatively correlated with age (P=0.001; R=-0.2), oxidative stress (P=0.008; R=-0.2), and severity of periodontitis (P=0.003; R=-0.2) in both the whole population and the subgroups (cases and controls). We conclude that shorter telomere lengths are associated with a diagnosis of periodontitis and their measures correlate with the oxidative stress and severity of disease.     

Serum copper,zinc and high-sensitivity C-reactive protein in short and long sleep duration in ageing men

BackgroundSerum levels of zinc and copper have been proposed to associate with sleep duration. Mechanisms, such as inflammatory processes, have been suggested to relate this association. However, earlier studies have been conducted in small sample sizes. Human studies investigating the suggested associations while controlling for potential confounding factors are lacking.MethodsPopulation-based data consisted of 2570 men (aged 42–60 years) from Eastern Finland. The participants reported an estimate of their sleep duration. The serum levels of zinc (S–Zn), copper (S–Cu) and high-sensitivity C-reactive protein (hs-CRP) were measured. Analysis of covariance was used for multivariate analyses.ResultsS–Zn levels and Zn/Cu ratio were lowest in ≤6 h sleep. S–Cu levels were highest in ≥10 h sleep. Elevated levels (>3.0 mmol/l) of hs-CRP were observed in ≤6 h and ≥10 h sleep. After adjustments for age, cumulative smoking history (pack-years), alcohol consumption (g/week), Human Population Laboratory depression scale scores, physical activity (kcal/day), cardiometabolic syndrome, and cardiovascular disease history, sleep duration was significantly associated with levels of both S–Cu and hs-CRP. The association with S–Cu remained statistically significant following further adjustment for hs-CRP in the same model.ConclusionsOur data suggests an association between S–Cu and sleep duration in ageing men. Elevated inflammation (measured as serum hs-CRP) does not explain this relationship. Mechanisms underlying the relationship require further investigation, as S–Cu may contribute to sleep regulation through pro-oxidative processes and copper-dependent N-methyl-d-aspartate receptor activity.     

Comparison of high-sensitivity C-reactive protein level between systemic and coronary circulation in patients with acute myocardial infarction

Inflammation plays an important role not only in the initi- ation and progression of atherosclerosis but also in plaque rupture of coronary artery disease （CAD） [ 1 - 3], which leads to acute coronary syndrome （ACS） or even acute myocardial infarction （AMI）. It is well known that C-reactive protein （CRP） is one of the most important inflammation markers and has been proved to be an independent risk factor for CAD [4-7]. High level of CRP predicts poor clinical out- comes in patients with both stable CAD and ACS [6-9]. Compared with CRP, high-sensitivity CRP （hs-CRP） is more sensitive that can be examined in serum. However, the source of CRP or hs-CRP in CAD or ACS has not been definitively explored.     

Interleukin-25 in sputum as a marker of airway inflammation in children asthma

<正>Dear Editor,Interleukin-25 (IL-25, also called IL-17E) is an important IL-17 family member that helps initialize and regulate type 2immunity, exerting an important influence on the pathogenesis of asthma (Corrigan et al., 2011; Barlow et al., 2012).Furthermore, it plays a vital role in initiating type 2 innate lymphoid cell activation and maintenance (Tong and Li,2018) and inducing Th2-type cytokine-mediated allergic airway eosinophilia (Morita et al., 2015). IL-25 expression     

Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study

BackgroundThere is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS.Methods and findingsWe conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin.Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor.ConclusionsThese multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation.Trial registrationClinicalTrials.gov - {"type":"clinical-trial","attrs":{"text":"NCT03507309","term_id":"NCT03507309"}}NCT03507309

Amit Kaura and colleagues investigate whether mildly elevated high sensitivity C-reactive protein is associated with mortality risk in patients with suspected acute coronary syndromes.     

Green fluorescent protein as a marker in transgenic mice

Green fluorescent protein (GFP) found in Aequorea victoria absorbs blue light and emits green fluorescence without exogenous substrates or co-factors. We studied the possibility of using the GFP as a marker in mammals. Transgenic mice were produced using the GFP coding sequence, ligated with the chicken beta-actin promoter. Green fluorescence was observed in muscle, pancreas, kidney, heart and other organs in all the three transgenic mouse lines. Detection of the transgenic mouse was possible by observing a tail or fingers of new born pups under a fluorescent microscope. The marker also enabled us to detect localized expression of the transgene in intact tissues without preliminary steps. It was also demonstrated that the GFP expression could be quantified by measuring the fluorescence in tissue extracts.     

Green fluorescent protein as a molecular marker in microbiology

Molecular markers such as: lacZ (b-galactosidase), xylE (catechol 2,3-dioxygenase), lux (bacterial luciferase), luc (insect luciferase), phoA (alkaline phosphatase), gusA and gurA (beta-glucuronidase), gfp (green fluorescent protein), bla (beta-lactamase) and other antibiotic resistance markers, heavy metals resistance genes are commonly used in environmental microorganisms research (Errampaii et al., 1998; Kohler et al., 1999). Most of these markers require one or more substrates, complex media and/or expensive equipment for detection. The gfp gene is widely used as a marker because of its very useful properties such as high stability, minimal toxicity, non-invasive detection and the ability to generate the green light without addition of external cofactors and without application of expensive equipment. Various applications of that reporter gene were showed starting from monitoring of microorganism's survival in complex biological systems such as activated sludge to biodegradation of chemical compounds in soil. GFP allowed the detection, determination of spatial location and enumeration of bacterial cells from diverse environmental samples such as biofilm and water. The gfp as a biomarker was very useful in monitoring of gene expression and protein localisation in bacterial cells, too. The techniques with using gfp marker promise to supply a better understanding of environmental processes. It can make possible to use that knowledge in designing more effective and more efficient methods of biodegradation of toxic compounds from different environments.     

Associations of plasma high-sensitivity C-reactive protein concentrations with all-cause and cause-specific mortality among middle-aged and elderly individuals

Background

The plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is a strong predictor of disease development and premature mortality in the general population. Unhealthy lifestyle habits such as smoking or unhealthy eating is known to elevate the suPAR level. We aimed to investigate whether change in lifestyle habits impact on the suPAR level, and whether the resultant levels are associated with mortality.

Results

Paired suPAR measurements from baseline- and the 5-year visit of the population-based Inter99 study were compared with the habits of diet, smoking, alcohol consumption, and physical activity. Paired suPAR measurements for 3225 individuals were analyzed by linear regression, adjusted for demographics and lifestyle habits. Compared to individuals with a healthy lifestyle, an unhealthy diet, low physical activity, and daily smoking were associated with a 5.9, 12.8, and 17.6% higher 5-year suPAR, respectively. During 6.1 years of follow-up after the 5-year visit, 1.6% of those with a low suPAR (mean 2.93 ng/ml) died compared with 3.8% of individuals with a high suPAR (mean 4.73 ng/ml), P <  0.001. In Cox regression analysis, adjusted for demographics and lifestyle, the hazard ratio for mortality per 5-year suPAR doubling was 2.03 (95% CI: 1.22–3.37).

Conclusion

Lifestyle has a considerable impact on suPAR levels; the combination of unhealthy habits was associated with 44% higher 5-year suPAR values and the 5-year suPAR was a strong predictor of mortality. We propose suPAR as a candidate biomarker for lifestyle changes as well as the subsequent risk of mortality.

     

Association between the AGTR1 polymorphism +1166A>C and serum levels of high-sensitivity C-reactive protein

Genetic factors have been shown to influence high-sensitivity C-reactive protein (hsCRP) levels, however, which genes that are involved in this process remains to be clarified. The renin–angiotensin system (RAS) is of importance for the regulation of inflammation, and blockade of angiotensin II type 1 receptors (AGTR1) influences hsCRP levels. These findings prompted us to investigate whether a polymorphism in the AGTR1 gene may influence hsCRP levels. Additionally, a polymorphism in the CRP gene that has previously been shown to influence hsCRP levels was genotyped. Serum levels of hsCRP were measured in 270 42-year-old women recruited from the population registry. Two single nucleotide polymorphisms were analysed: +1166A>C and +1444C>T of the AGTR1 and CRP gene, respectively. The A allele of the AGTR1 polymorphism +1166A>C was dose-dependently associated with higher hsCRP levels (p = 0.014, adjusted for confounding factors and multiple comparisons). hsCRP levels were not significantly influenced by the CRP +1444C>T genotype; however, an interaction between the two studied polymorphisms with respect to hsCRP levels was observed (p = 0.018). The significant association between the AGTR1 polymorphism and hsCRP levels, which appears to be independent of anthropometric and metabolic traits, is yet another indication of a direct influence of RAS on inflammation.