C-Reactive protein gene variants are associated with postoperative C-reactive protein levels after coronary artery bypass surgery

Background  

Elevated baseline C-reactive protein (CRP) levels are associated with increased risk for developing cardiovascular disease. Several CRP gene variants have been associated with altered baseline CRP levels in ambulatory populations. However, the influence of CRP gene variants on CRP levels during inflammatory states, such as surgery, is largely unexplored. We describe the association between candidate CRP gene variants and postoperative plasma CRP levels in patients undergoing primary, elective coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB).     

Concurrent infections are important for expression of porcine circovirus associated disease

Porcine circovirus type 2 (PCV2) is the essential component of porcine circovirus disease (PCVD) as the disease syndrome is referred to in Europe and porcine circovirus associated disease (PCVAD) as it is referred to in North America. Singular PCV2 infection rarely results in clinical disease; however, PCVAD is often accelerated in onset, enhanced in severity and prolonged in duration by concurrent viral or bacterial infections. Due to its effect on the immune system, PCV2 has also been shown to enhance protozoal, metazoal, and fungal infections. Several retrospective or cross-sectional studies have investigated the presence and prevalence of various infectious agents associated with PCVAD under field conditions. Experimental models confirm that PCV2 replication and associated lesions can be enhanced by concurrent infection with other viruses or bacteria. The exact mechanisms by which concurrent pathogens upregulate PCV2 are unknown. Co-infections may promote PCV2 infection by increasing immune host cell replication and accumulation in tissues thereby enhancing targets for PCV2 replication. It has also been proposed that co-infections interfere with PCV2 clearance by alteration of cytokine production and profiles. The outcome of differences in timing of co-infections in PCV2-infected pigs is also likely very important and is an area where more research is needed. Given the current knowledge base, it is important that veterinarians do a thorough diagnostic investigation on herds where PCVAD is a recurrent problem in order to implement the most appropriate and cost effective intervention strategies.     

Adiponectin levels are associated with coronary artery disease across Caucasian and African-American ethnicity

The hypothesis was tested that plasma levels of adiponectin would be associated with coronary artery disease (CAD) across African-American and Caucasian ethnicity and gender. Adiponectin levels, cardiovascular risk factors, and extent of CAD were measured in 453 subjects (173 African-American and 280 Caucasian men and women). The distribution of adiponectin levels differed significantly between African-Americans and Caucasians (P<0.0001). Among African-Americans, the adiponectin distribution was skewed toward lower levels. For women, adiponectin levels were higher among Caucasians compared with African-Americans (P<0.001), whereas no interethnic difference was observed for men. Irrespective of ethnic group, subjects with CAD had lower levels of adiponectin than did subjects without CAD. Adiponectin was negatively and significantly associated with waist-hip ratio, body mass index, diastolic blood pressure, insulin level, and homeostasis model assessment-insulin resistance in both ethnic groups. Among lipid parameters, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were negatively correlated with adiponectin, whereas the high-density lipoprotein cholesterol level correlated positively for both African-Americans and Caucasians. In a multiple regression model, controlling for gender, ethnicity, and other CAD risk factors, adiponectin levels were negatively associated with CAD (P<0.05). The results indicate that, across gender and ethnicity, low adiponectin levels may be an independent risk factor for CAD.     

Development of a high sensitivity C-reactive protein immunoassay and comparison with a commercial kit

C-reactive protein (CRP) is intricately sensitive marker of inflammation, infection, and tissue damage. Role in the prognosis of heart diseases has been recently discovered. This study aimed to develop a cost-effective and high-sensitivity CRP immunoassay for use in cardiac risk assessment. Assay was optimized for coating, blocking of capturing antibody, dilution, and reaction time of the conjugate and sample volume. For normal reference range, CRP was determined in serum samples from apparently healthy volunteers. For clinical validation, CRP was determined in samples of acute coronary syndrome patients by in-house and commercial assays. The lower detection limit of in-house assay was 0.16 µg/L. Intra and inter assay imprecision was 4.39%, 4.6% and 8.6%, 9.3%, respectively. The correlation between the CRP levels by the two assays was r = 0.861. Sensitivity, specificity, predictive value for a positive test, and a negative test of in-house assay was 95.3%, 92.8%, 95.3%, and 92.8%, respectively. At lower-end CRP levels of both kits correlated very well but showed variation at upper end. In-house assay showed high sensitivity and reliability at lower end and it is hoped that will help to evaluate cardiac risk assessment (after improvement at upper end) in clinically poor settings.     

Cholesteryl ester transfer protein gene polymorphisms are associated with coronary artery disease in Corsican population (France)

The aim of the present study was to investigate the association between coronary artery disease (CAD) and Cholesterol Ester Transfer Protein (CETP) (gaaa)n polymorphisms of the CETP gene in Central Corsica island (France). The study group was composed by 300 unrelated Corsican patients with angiographically documented CAD and 300 unrelated healthy blood donors. Significant differences were observed in the distribution of CETP (gaaa)n alleles between the groups under study (p=0.03; chi(2): 16.8, df: 8). The occurrence of a long allele (408 bp) was higher in cases (12%) than in control group (2%), showing a 6.75-fold increased risk for CAD in Corsica patients (p=0.0055; OR=6.750; 95% CIs=1.47-31.00). The correlation of this polymorphism with the lipid profile (cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides) in the patients group was determined. There was a significant association of the long alleles of CETP (gaaa)n with HDL-C levels. In the patient and in the control groups the LL genotypes had lower HDL-C compared with the SS and SL genotypes (p<0.0001). In summary our results suggest that the genetic variation at the CETP gene may play an important role in determining CAD in Corsican population.     

Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease

BACKGROUND:

To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome.

MATERIALS/METHODS:

We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35).

RESULTS:

We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups.

DISCUSSION:

The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process.     

血清胱抑素C、超敏C反应蛋白表达水平对急性冠脉综合征的临床诊断价值

目的 探讨血清超敏C反应蛋白（hs-CRP）、胱抑素（Cys-C）表达水平对急性冠脉综合征（ACS）的临床诊断价值.方法 选取入住我院心内科134例ACS患者,其中稳定型心绞痛患者（SA）60例,不稳定型心绞痛患者（UAP）52例,急性心肌梗死（AMI）患者22例,同时健康体检者62例,测定各组hs-CRP、Cys-C l以及相关性因子的水平,并进行统计学分析.结果 ①ACS患者hs-CRP（mg/L）（SA组：4.87 ±0.65、UAP组：9.81 ±1.13、AMI组：20.27±2.36、对照组1.24±0.52）、Cys-C （mg/L）（SA组：0.76±0.13、UAP组：1.03±0.17、AMI组：1.39±0.36、对照组0.46±0.07、基质金属蛋白酶（MMP）-9（μg/mL）（SA组：308.43±35.52、UAP组：379.86±27.90、AMI组：420.13±50.16、对照组112.07±10.18）以及IL-6 （pg/L）（SA组：62.37±5.18、UAP组：69.05±7.18、AMI组：72.53±6.95、对照组27.19±3.96）表达水平明显升高,差异具有统计学意义（P＜0.05）,内皮细胞一氧化氮合酶（eNOS）（μmol/L）（SA组：22.84±2.65、UAP组：19.43±1.79、AMI组：7.93±1.17、对照组30.19±3.53）水平相对于对照组降低,差异有统计学意义（P＜0.05）;②ACS血清hs-CRP表达与Cys-C,MMP-9,eNOS相关（P＜0.05）,Cys-C与MMP-9、eNOS、IL-6表达具有相关性（P＜0.05）;③SA组、UAP组以及AMI组血清hs-CRP、Cys-C表达水平依次升高,差异具有统计学意义（P＜0.05）.结论 血清hs-CRP、Cys-C表达对于诊断ACS可能具有临床意义.     

冠心病与蛋白Z内含子FG79A基因多态性无关联

目的：探讨中国浙江地区汉族人群中蛋白Z（protein Z, vitamin K-dependent plasma glycoprotein，PROZ）内含子FG79A基因多态性的发生率及其与冠心病的关系。〖HJ2.1mm〗方法:对冠状动脉粥样硬化性心脏病（简称冠心病）组（至少1支冠脉动脉直径狭窄≥50%）148例和147例对照者采用聚合酶链反应和限制性内切酶片段长度多态性方法结合基因测序技术，检测蛋白Z内含子FG79A基因多态性。结果:首次发现中国浙江地区汉族人群存在蛋白Z内含子FG79A基因多态性，野生型（GG型）、GA型和AA型分别占16.95%、 54.58%和28.47%；G、A等位基因频率分别为44.24%和55.76%；冠心病组与对照组间基因型和等位基因频率分布差异均无显著性意义（均P>0.05）；冠脉单支、双支和三支病变患者间基因多态性分布差异无显著性意义（P>0.05），蛋白Z内含子FG79A基因型和等位基因频率在急性冠脉综合征和非急性冠脉综合征患者间的分布差异亦无显著性意义（均P>0.05）。结论:中国浙江地区汉族人群存在蛋白Z内含子FG79A基因多态性，但蛋白Z内含子FG79A基因多态性与冠心病及急性冠脉综合症的发生无关。     

Prior infections are associated with increased mortality from subsequent blood-stream infections among patients with hematological malignancies

Many patients who are evaluated and treated for sepsis have histories of recent infections. The prognostic implications of surviving an infectious process are not well understood. We undertook this study to determine the clinical impact of prior infections among patients with hematological malignancies, a population at high risk for developing and dying from sepsis. The medical records of 203 patients with hematological malignancies and blood-stream infections admitted over a 3-year period to an urban teaching hospital were retrospectively reviewed. The 30-day mortality after blood-stream infection in these high-risk patients was 24 %. There were 46 patients (23 %) who had inpatient infections in the 90 days prior to the index blood-stream infection. History of recent infection portended worse prognosis from blood-stream infection under multivariable analysis [odds ratio (OR) 2.60, p?=?0.04, 95 % confidence interval (CI) 1.04–6.47]. There were 86 patients (42 %) who had subsequent infections in the first 90 days after the index blood-stream infection. Patients with subsequent infections had greater mortality during days 91–365 than patients without subsequent infections [hazard ratio (HR) 1.97, p?=?0.02, 95 % CI 1.13–3.44]. Recent infections prognosticate worse outcomes from subsequent blood-stream infections for this high-risk population. Further research into the clinical and biochemical reasons for this observation may lead to targets for intervention, and, ultimately, improvements in long-term mortality from sepsis.     

MASP2 haplotypes are associated with high risk of cardiomyopathy in chronic Chagas disease

Mannose-binding lectin (MBL) initiates complement on Trypanosoma cruzi through the MBL-associated serine protease 2 (MASP2). We haplotyped six MASP2 polymorphisms in 208 chronic chagasic patients, being 81 indeterminate and 123 symptomatic (76 with cardiac, 19 with digestive and 28 with cardiodigestive forms) and 300 healthy individuals from Southern Brazil, using PCR with sequence-specific primers. The g.1961795C, p.371D diplotype (short CD) occurred at a higher frequency among symptomatic patients, compared with the indeterminate group (P(Bf)=0.012, OR=3.11), as well as genotypes with CD, but not with the g.1945560A in the promoter in cardiac patients (P(Bf)=0.012, OR=13.54). CD haplotypes linked to the p.P126L and p.V377A variants were associated with reduced MASP-2 levels (P<0.0001) but not reduced MBL/MASP-2/C4 complexes. MASP2*CD genotypes, most of them generating low MASP-2 levels, are associated with high risk of chagasic cardiomyopathy. Rapid MASP2 genotyping might be used to predict the risk of symptomatic disease.     

C-reactive protein: general review and role in the study of infections

Known since 1930, C-reactive protein is, as serum amyloid P component its similar, part of acute phase response proteins. Its principals properties are short half-life (6-8 h), great (within 6 hours) and high (X500) rate after injury. It activates the classical complement pathway, leading further to bacterial opsonization. Different biological methods for measurement are described: both nephelometric laser method, most sensible, and agglutination-latex method, most simple and quickest, are chosen. Studies showed us that CRP value is interesting for diagnosis of bacterial infections: among them neonates infections, peri-partum infections, meningitis, pyelonephritis, pancreatitis or peritonitis. CRP value determination seems to be useful also to hold on with patients who keep infectious peril, as in post chirurgical following, neutropenic induced patients. It seemed to be no use for CRP measurement in grafts following. Its rate in inflammatory diseases or myocardial infarcts is just mentioned. The author precognize more determinations of CRP: in emergency laboratories for diagnosis of bacterial infections (agglutination latex method) and in "routine" to follow up the infectious peril.     

The association between chronic osteomyelitis and increased risk of diabetes mellitus: a population-based cohort study

Chronic inflammation is a well-known risk factor for type 2 diabetes mellitus (T2DM). The influence of chronic osteomyelitis (COM), an inflammatory disease, on the risk of developing T2DM remains unknown. This study investigated the risk of developing T2DM among COM patients. Using a retrospective cohort study, we identified 20,641 patients with COM and 82,564 age- and sex-matched controls for comparison from the Taiwan National Health Insurance Database (NHIRD) from 1997 to 2010. We followed up the COM cohort and the comparison cohort to compare the incidences of diabetes (ICD-9-CM code 250) until the end of 2010 or until the patients were censored because of death or withdrawal from the insurance program. The diabetes risk was analyzed using the Cox proportional hazards regression model. The incidence of T2DM was 1.6-fold higher in the group of COM patients than in the comparison group (29.1 vs. 18.2 per 10,000 person-years). The COM patients exhibited a higher diabetes risk [adjusted hazard ratio (aHR)?=?1.64, 95 % confidence interval (CI)?=?1.44–1.87] after controlling for the baseline and comorbidities. Younger and higher income patients exhibited a higher COM-to-reference incidence rate ratio (IRR) for T2DM compared with that of their counterparts. We also observed an increased risk of T2DM in COM patients with comorbidities (aHR?=?1.70, 95 % CI?=?1.47–1.96) compared with that of their non-COM counterparts. This is the first study to report the association between COM and an increased risk of developing T2DM, particularly among younger and higher income patients.     

Baseline C-reactive protein level as a predictor of mortality in bacteraemia patients: a population-based cohort study

We examined the association between C-reactive protein (CRP) level at time of blood culture (BC) draw and mortality following bacteraemia. Our population-based cohort study comprised all first-time monomicrobial bacteraemia episodes in adults in a Danish county during 1996–2004 (n = 5267). CRP was measured within 24 h of the first positive BC draw. Cox regression was used to compute mortality rate ratios (MRRs) associated with CRP level quartiles (10–64 (reference), 65–143, 144–240 and 241–688 mg/L), controlling for age, gender, comorbidity, specialty, acquisition of infection, and infection focus. We also looked for a biological interaction between CRP level and high magnitude of bacteraemia (three of three culture bottles positive). Thirty-day mortality increased with higher CRP level: adjusted 0–30-day MRRs for patients in the second, third and fourth CRP quartiles were 1.38 (95% CI 1.13–1.69), 1.70 (95% CI 1.40–2.06), and 2.38 (95% CI 1.96–2.87), respectively (p for trend <10⁾⁴). In contrast, mortality associations with CRP during 31–365 days of follow-up were weak (adjusted MRRs for the second to fourth quartiles ranged from 1.18 to 1.28). A high magnitude of bacteraemia strengthened the association between high CRP level and 30-day mortality. We conclude that the CRP level, measured concurrently with the first positive BC, independently predicted 30-day mortality in adult bacteraemia patients.     

Comorbidities of chronic obstructive pulmonary disease in koreans: a population-based study

Chronic obstructive pulmonary disease (COPD) includes pulmonary components with increased comorbidity rates, as well as being a systemic disease. Comorbidities may frequently occur in COPD patients over 40 yr old. We report the comorbidities of patients with COPD, diagnosed by spirometry, in a population-based epidemiologic survey in Korea. Data were derived from the fourth Korean Health and Nutrition Examination Survey in 2008, a stratified multistage clustered probability design survey of a sample representing the entire population of Korea. Results of spirometry and various health-related questionnaires were analyzed in 2,177 subjects aged ≥ 40 yr. The prevalence of COPD (FEV(1)/FVC < 0.7) in subjects ≥ 40 yr of age was 14.1%. Multivariate analysis showed that underweight (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.05-8.98), coronary heart disease (OR, 0.43; 95% CI, 0.20-0.93) and dyslipidemia (OR, 0.61; 95% CI, 0.45-0.82) were significantly associated with COPD, whereas allergic rhinitis, anemia, arthritis, chronic renal failure, depression, diabetes mellitus, hypertension, gastrointestinal ulcer, and osteoporosis were not. Underweight might be more prevalent but coronary heart disease and dyslipidemia are less prevalent in Koreans with than without COPD in population setting.     

超敏C反应蛋白与冠心病相关性研究进展

冠心病的炎症学说逐渐得到大家认可。许多基础和临床研究证实超敏c反应蛋白（high—sensitivity C-reactive protein,hs—CRP）不仅是炎症的非特异性标志物,本身亦直接参与心血管疾病的病理过程。hs-CRP对于冠心病的诊断和治疗具有重要指导意义,尤其是可以作为健康人冠心病风险的有效预测因子。本文综述hs-CRP与冠心病的关系及致病机制的研究进展。