Showing papers on "C-reactive protein published in 1996"

Relation of C-Reactive Protein and Coronary Heart Disease in the MRFIT Nested Case-Control Study

Abstract: The authors measured the relation between C-reactive protein, alpha 1 acid glycoprotein and albumin, an acute phase protein, and subsequent risk of myocardial infarction and coronary heart disease death in a nested case-control study among the Multiple Risk Factor Intervention Trial (MRFIT) participants There were 98 myocardial infarction cases, 148 coronary heart disease deaths, and 491 controls The cases and controls were followed for up to 17 years for deaths and 6-7 years for myocardial infarction cases and controls There was a significant association between available distribution of C-reactive protein and subsequent coronary heart disease mortality For smokers at baseline, the risk of coronary heart disease deaths in quartile 4 of C-reactive protein as compared with quartile 1 was 43 (95% confidence interval 174-108) The association persisted when adjusted for characteristics related to smoking and smoking cessation during the trial and to pulmonary function There was no relation between alpha 1 acid glycoprotein and either myocardial infarction or coronary heart disease death Albumin was inversely related to coronary heart disease death only for deaths that occurred between 7 and 13 years after baseline, consistent with previous MRFIT analyses This is the first prospective study in "healthy but high risk individuals" to document the relation between C-reactive protein and coronary heart disease mortality

C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study.

Abstract: Objective: To test the hypothesis that minor chronic insults such as smoking, chronic bronchitis, and two persistent bacterial infections may be associated with increases in C reactive protein concentration within the normal range and that variations in the C reactive protein concentration in turn may be associated with levels of cardiovascular risk factors and chronic coronary heart disease. Design: Population based cross sectional study. Setting: General practices in Merton, Sutton, and Wandsworth. Subjects: A random sample of 388 men aged 50-69 years from general practice registers. 612 men were invited to attend and 413 attended, of whom 25 non-white men were excluded. The first 303 of the remaining 388 men had full risk factor profiles determined. Interventions: Measurements of serum C reactive protein concentrations by in house enzyme linked immunosorbent assay (ELISA); other determinations by standard methods. Coronary heart disease was sought by the Rose angina questionnaire and Minnesota coded electrocardiograms. Main outcome measures: Serum C reactive protein concentrations, cardiovascular risk factor levels, and the presence of coronary heart disease. Results: Increasing age, smoking, symptoms of chronic bronchitis, Helicobacter pylori and Chlamydia pneumoniae infections, and body mass index were all associated with raised concentrations of C reactive protein. C Reactive protein concentration was associated with raised serum fibrinogen, sialic acid, total cholesterol, triglyceride, glucose, and apolipoprotein B values. C Reactive protein concentration was negatively associated with high density lipoprotein cholesterol concentration. There was a weaker positive relation with low density lipoprotein cholesterol concentration and no relation with apolipoprotein A I value. C Reactive protein concentration was also strongly associated with coronary heart disease. Conclusion: The body9s response to inflammation may play an important part in influencing the progression of atherosclerosis. The association of C reactive protein concentration with coronary heart disease needs testing in prospective studies. Key messages Factors that determine levels of inflammatory mediators in the normal general population have not been explored, nor has their relation to cardio- vascular risk factors Among 50-69 year old men many environmental and lifestyle risk factors for cardiovascular disease are associated with raised serum concentrations of C reactive protein Circulating concentrations of lipids, glucose, and clotting factors are also associated with serum C reactive protein concentrations The body9s response to inflammation may influence the development of atherosclerosis

Serum C-reactive protein concentration in acute myocardial infarction and its relationship to mortality during 24 months of follow-up in patients under thrombolytic treatment

Abstract: Objectives We studied the relationship between serum C-reactive protein and mortality in acute myocardial infarction. Background Early recanalization of an infarct-related coronary artery is considered to be an essential prerequisite for reducing mortality by thrombolytic treatment in acute myocardial infarction. It also reduces the inflammatory reaction caused by acute myocardial infarction and is measurable by determination of serum C-reactive protein concentrations. We therefore studied the prognostic value of determining serum C-reactive protein in acute myocardial infarction. Methods We measured serum C-reactive protein concentrations daily for 6 days and creatine kinase, as well as its MB isoenzyme concentrations twice a day, for 3 days after a myocardial infarct, in 188 consecutive patients selected for thrombolytic therapy and treated in the same University Hospital Coronary Care Unit. The highest serum concentrations were related to total mortality as well as to the causes of death 3, 3–6, 6–12 and 12–24 months after the onset of the myocardial infarction. Results The highest serum concentrations of serum C-reactive protein were observed 2 to 4 days after the onset of myocardial infarction. The mean value of the highest serum concentration of C-reactive protein in patients who survived the whole 24-month study period was 65 mg. l−1 with the 95% confidence intervals for the mean ranging from 58 to 71. The corresponding values in those who died within 3, 3–6, 6–12 and 12–24 months were 166 (139–194), 136 (88–184), 85 (52–119) and 74 (38–111) mg.l−1 respectively. The values in those who died within 3 and 3–6 months of the infarction differed statistically significantly from the values in those who survived the whole period ( P <0.001 and P <0.05, respectively). In patients who died due to congestive heart failure the mean highest serum C-reactive protein concentration was 226 (189–265) mg . l−1 In those who suffered sudden cardiac death and those who died from a new myocardial infarction or non-cardiac causes, the respective values were 167 (138–196), 64 (38–89) and 48 (10–86) mg. l−1. The values in those who died due to congestive heart failure and those suffering sudden cardiac death differed statistically significantly ( P <0.001) from the values of those who survived or died due to other causes. The highest serum concentrations of creatine kinase or its MB isoenzyme were not associated with mortality in this study. Conclusions High serum C-reactive protein concentrations in acute myocardial infarction patients treated with thrombolytic drugs predict increased mortality up to 6 months following the infarction. Accordingly, reduction of inflammatory reaction by successful thrombolytic treat ment may make an important contribution to the survival benefit of thrombolytic treatment of acute myocardial infarction.

Crp-mediated activation of complement in vivo : assessment by measuring circulating complement-c-reactive protein complexes

Abstract: The in vivo function of C-reactive protein (CRP) is unknown Among the in vitro functions assigned to CRP is the ability to activate complement via the classical pathway To date, there is no evidence supporting that CRP exerts this function in vivo We here show a novel approach to assess CRP-mediated complement activation in vivo, which is based on the property that activated complement factors C3 and C4 fix to CRP during complement activation induced by this acute phase protein We developed specific ELISAs for complexes between CRP and C4b, C4d, C3b, or C3d We established that in vitro complement-CRP complexes were formed only during CRP-dependent activation, and not during activation by other activators, even in the presence of high CRP levels Circulating levels of complement-CRP complexes were undetectable in normal donors, but significantly increased in nine patients following implantation of a renal allograft Importantly, levels of complement-CRP complexes did not change in these patients upon a bolus infusion of mAb OKT3, which induces activation of the classical complement pathway, demonstrating in vivo that complement-CRP complexes are not formed during CRP-independent activation of complement, even when CRP is elevated We conclude that measurement of complement-CRP complexes provides a suitable tool to study CRP-mediated activation of complement in vivo Furthermore, increased levels of these complexes occur in clinical samples, indicating that CRP may induce activation of complement in vivo

Expression of C-reactive protein by alveolar macrophages.

Abstract: C-reactive protein (CRP) is well characterized as one of the serum acute phase proteins, the levels of which increase dramatically after infection. CRP has been shown to be involved in multiple immunoregulatory functions. For example, it activates the classical complement cascade, opsonizes bacteria for phagocytosis, and stimulates phagocytic cells. Although CRP is predominantly produced and secreted by hepatocytes, other cells including subsets of lymphocytes, Kupffer cells, and blood monocytes have been shown to synthesize this protein as well. We hypothesized that CRP may be produced in the lung, and therefore it could function directly in pulmonary host defense. Western blot analysis showed that CRP was present in the lung tissue, lung lavage, and alveolar macrophages. This result was further confirmed by immunohistochemical staining of lung sections that showed the localization of CRP in alveolar macrophages. The CRP mRNA was detected subsequently by reverse-transcriptase PCR (RT-PCR), and a single amplified product was obtained from alveolar macrophages as well as from whole lung tissue. Both were the same size as the amplified product obtained from liver mRNA. Furthermore, in situ hybridization with CRP riboprobe demonstrated specific staining of alveolar macrophages both in lung sections and isolated cells. In addition, in situ hybridization showed that CRP mRNA levels in isolated alveolar macrophages were up-regulated by in vitro LPS stimulation. In summary, these results indicate that CRP is produced by alveolar macrophages, and suggest that CRP may be involved in the pulmonary immune response.

Role of complement in C-reactive-protein-mediated protection of mice from Streptococcus pneumoniae.

Abstract: Expression of a human C-reactive protein (CRP) transgene has been shown to protect mice from lethal Streptococcus pneumoniae infection. In the present study, we used cobra venom factor-induced decomplementation to investigate the role of complement in this CRP-mediated protection. An intact complement system significantly reduced pneumococcal bacteremia at 24 h postinfection and extended median survival time of both CRP-transgenic and nontransgenic mice. However, mortality was significantly lowered only for CRP transgenic mice. The transgene significantly reduced bacteremia for both normocomplementemic and decomplemented mice, but it resulted in a significantly longer median survival time and lower mortality only for normocomplementemic mice. These data suggest that in vivo complement and CRP amplify each other's protective capacity, particularly during the early course of infection.

Evaluation of tissue trauma after laparoscopic and abdominal hysterectomy: measurements of neutrophil activation and release of interleukin-6, cortisol, and C-reactive protein.

Abstract: Background Trauma and major surgery stimulate a cascade of events that mediate the inflammatory response The aim of our study was to determine whether or not hysterectomy leads to release of cytokines, cortisol, and C-reactive protein (CRP), activation of neutrophils, and activation of the complement cascade A further aim was to compare laparoscopic and abdominal hysterectomy with regard to the same parameters Study design Twenty-four consecutive patients were randomized to either abdominal (n = 12) or laparoscopic hysterectomy (n = 12) Blood samples were drawn preoperatively, intraoperatively, and then at one minute, 24 hours, and seven days postoperatively Interleukin-6 (IL-6) levels were used to evaluate cytokine release, cortisol and CRP to evaluate the inflammatory response, and polymorphonuclear (PMN) elastase to detect neutrophil activation To evaluate complement activation, the terminal C5b-9 complement complex (TCC) was determined Results Interleukin-6 concentrations were significantly elevated one minute and 24 hours postoperatively in both groups Independent of the surgical technique or operative time, the highest IL-6 concentration was reached four hours after beginning the operation Cortisol levels were significantly elevated during and after the operation in both groups C-reactive peptide levels were significantly elevated in both groups 24 hours and seven days after the operation Polymorphonuclear elastase was elevated 24 hours postoperatively in both groups There were no signs of complement activation during the operative period or postoperatively in either patient group Conclusions Our results indicate serious tissue trauma during both laparoscopic and abdominal hysterectomy The extent of surgical trauma did not differ between the two operative methods

ORIGINAL CONTRIBUTIONS Relation of C-Reactive Protein and Coronary Heart Disease in the MRFIT Nested Case-Control Study

Abstract: The authors measured the relation between C-reactive protein, a., acid glycoprotein and albumin, an acute phase protein, and subsequent risk of myocardial infarction and coronary heart disease death in a nested case-control study among the Multiple Risk Factor Intervention Trial (MRFIT) participants. There were 98 myocardial infarction cases, 148 coronary heart disease deaths, and 491 controls. The cases and controls were followed for up to 17 years for deaths and 6-7 years for myocardial infarction cases and controls. There was a significant association between available distribution of C-reactive protein and subsequent coronary heart disease mortality. For smokers at baseline, the risk of coronary heart disease deaths in quartile 4 of C-reactive protein as compared with quartile 1 was 4.3 (95% confidence interval 1.74-10.8). The association persisted when adjusted for characteristics related to smoking and smoking cessation during the trial and to pulmonary function. There was no relation between a-, acid glycoprotein and either myocardial infarction or coronary heart disease death. Albumin was inversely related to coronary heart disease death only for deaths that occurred between 7 and 13 years after baseline, consistent with previous MRFIT analyses. This is the first prospective study in "hearthy but high risk individuals" to document the relation between C-reactive protein and coronary heart disease mortality. Am J Epidemiol 996;144:537-47. acute phase proteins; albumins; coronary disease; C-reactive protein; orosomucoid; smoking

Transgenic mice expressing rabbit C-reactive protein exhibit diminished chemotactic factor-induced alveolitis.

Abstract: The acute phase protein, C-reactive protein (CRP), can increase more than a thousandfold during acute inflammatory states, and it is known to modulate neutrophil-mediated inflammatory responses. We have previously shown that CRP inhibits chemotaxis of C5a-stimulated neutrophils in vitro and that rabbits with elevated CRP blood levels exhibit diminished pulmonary vascular permeability and neutrophil infiltration in a model of alveolitis. To study the effect of CRP on alveolitis induced by different chemoattractants, transgenic mice capable of expressing rabbit CRP in a dietary-inducible fashion were treated with inflammatory doses of the chemoattractants. Intratracheal installation of FMLP (8 x 10(-10) mol), LTB4 (2 x 10(-11) mol), or IL-8 (5 x 10(-12) mol) in normal CF1 mice resulted in significant (p<0.05) influx of neutrophils and protein into the alveolar space. Transgenic mice with elevated plasma levels of CRP showed significantly (p<0.05) diminished infiltration of neutrophils into bronchoalveolar l...

Inflammation in ischaemic heart disease.

Abstract: Recent reports have suggested a link between blood concentrations of C reactive protein and the risk of cardiovascular disease The ECAT study (European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study) followed 3000 people with chronic stable ischaemic heart disease for three years and found a significant correlation between concentrations of C reactive protein within the normal range and long term cardiovascular risk1 Raised concentrations have also been shown to be strong prognostic indicators in patients with unstable angina,2 and in this week's BMJ Mendall et al report an association between C reactive protein concentrations and indirect evidence of ischaemic heart disease (p1061)3 What are the pathogenetic implications of this novel marker of acute and chronic manifestations of ischaemic heart disease and its relevance in clinical practice? Mendall et al studied 303 men aged 50-69 years selected from general practice registers3 and found that the prevalence of indirect evidence of ischaemic heart disease and a history of claudication (together with age, smoking, chronic bronchitis, and most traditional cardiovascular risk factors) increased progressively as blood concentrations of C reactive protein rose This correlation between C reactive protein and traditional risk factors for ischaemic heart disease may influence prognosis in the long term by favouring the development of atherosclerosis, but the prognostic value of C reactive protein might also result from an increased incidence and worse outcome of …

Glutathione reductase activity, riboflavin status, and disease activity in rheumatoid arthritis.

Abstract: OBJECTIVE: To measure erythrocyte glutathione reductase (EGR) activity and riboflavin status, and their relations to disease activity, in rheumatoid arthritis patients compared to healthy controls. METHODS: Patients with rheumatoid arthritis were classified as active if there were features of articular inflammation which required initiation or change of disease modifying therapy, and as inactive if they had little evidence of articular inflammation. EGR was measured in patients and healthy controls by a functional assay with or without the addition of flavin adenine dinucleotide (FAD). The ratio of stimulated EGR (with FAD added) to basal EGR (no added FAD), which measures riboflavin status, is known as the EGR activation coefficient (EGRAC). An EGRAC > or = 1.3 represents biochemical riboflavin deficiency. RESULTS: 91 patients with rheumatoid arthritis, including 57 with active disease, and 220 healthy controls were studied. Both basal and stimulated EGR were significantly higher in patients with rheumatoid arthritis (P = 0.0001) than in controls. Biochemical riboflavin deficiency was identified in 41% controls and 33% patients with active rheumatoid arthritis but was significantly less frequent (9%) in patients with inactive compared to active disease (P = 0.02) or healthy controls (P = 0.0006). Pain score, articular index, C reactive protein, and erythrocyte sedimentation rate were increased in patients with riboflavin deficiency (all P < 0.02). CONCLUSIONS: Higher basal and stimulated EGR might be expected in patients with rheumatoid arthritis in response to chronic oxidative stress due to synovial inflammation. The association of riboflavin deficiency with increased disease activity suggests that impaired EGR activity could facilitate continuing inflammation in these patients.

Pre-operative plasma levels of C-reactive protein, albumin and various plasma protease inhibitors for the pre-operative assessment of operability and recurrence in cancer surgery

Abstract: Pre-operative levels of the acute phase protein C-reactive protein (CRP), albumin (assessing nutritional status), the tumour marker CEA and three plasma protease inhibitors, i.e. C1-esterase inhibitor, alpha-2-macroglobulin and antithrombin III, were prospectively studied in 183 patients with various solid cancers. First, the predictive value of abnormal levels for operability at the primary operation was studied. Secondly, the predictive value of abnormal levels for cancer recurrence and metastases was evaluated during 2 years of follow-up. The results show that malignancy induces increased CRP and C1-esterase inhibitor levels and decreased albumin levels in serum. These changes, as well as raised alkaline phosphatase and lowered haemoglobin levels, also correlate to the ‘overall’ tumour burden. The most important conclusion is, that increased pre-operative CRP levels (CRP ≥ 10 mg/l; sensitivity, 79%; specificity, 71%) and/or low albumin levels (albumin 152%; sensitivity, 45%; specificity, 90%), and in some patients a high alkaline phosphatase level, are seen in patients exhibiting early cancer recurrence (within 2 years post-operatively).

Relation of C reactive protein to cardiovascular risk factors. H pylori and C pneumoniae infections may account for most acute coronary syndromes.

Abstract: EDITOR,—M A Mendall and colleagues provide data showing a strong association between C reactive protein concentration (a sensitive marker of systemic inflammation) and coronary heart disease.1 This finding draws attention to the inflammation as a mechanism underlying the progression of ischaemic heart disease. The same authors have previously shown a greatly increased cardiovascular risk in subjects with Helicobacter pylori and Chlamydia pneumoniae infections.2 Recently we measured serum levels of antibody to H pylori and C pneumoniae in patients …

Lipoprotein(a) in 505 hospitalized patients with various pathological states: correlations with cardiovascular diseases and therapies.

Abstract: Objective Our aim was to study the lipoprotein (a) (Lp(a)) levels in various pathological states. Experimental design This investigation was prospective and included a healthy control group. Setting This study was carried out in two internal medicine and angiology services in teaching hospitals. Patients 505 patients were included with various diseases: 66 acute infections, 9 HIV infections, 25 cancers, 86 diabetes, 36 systemic diseases, 94 atheromatous vascular disease, 27 arterial hypertensions. A control group was composed of 21 healthy subjects. Interventions There was no therapeutic intervention but cardiovascular treatments were recorded. Measures Serum Lp(a), total cholesterol, triglycerides, HDL-cholesterol, calculated LDL-cholesterol, apolipoproteins A-I and B were measured together with inflammatory parameters, serum creatinine, proteinuria, serum aminotransferase activity. Results There was no difference in Lp(a) levels between controls and each patient group. However, a correlation was found in systemic diseases between Lp(a) and C reactive protein (r = 0.371, p = 0.026) or serum albumin concentration (r = 0.453, p = 0.006). In hypertension, Lp(a) correlated with serum creatinine (r = 0.420, p = 0.03). In the whole patient population, Lp(a) was correlated with cholesterol (r = 0.156, p = 0.0001), apolipoprotein B (r = 0.215, p = 0.0001), age (r = 0.108, p = 0.015), arterial events (r = 0.174, p = 0.0001) and platelet anti-aggregant drugs (r = 0.169, p = 0.0001). Conclusions Lp(a), was related to atheromatous events and in systemic diseases to inflammation, suggesting that Lp(a) might vary in some patients in a manner similar to acute phase proteins.

[Clinical significance of cytokines Il-6, Il-8 and C-reactive protein in serum of patients with acute pancreatitis]

Abstract: The detection of cytokines may elucidate the pathophysiological mechanisms that produce early systemic complications in acute interstitial (i) or necrotizing (n) pancreatitis (AP). The increase in the level of cytokines in the blood of patients with AP may correlate with the severity of the disease. In a prospective clinical trial from October 1992 to August 1993, 23 patients with AP were recruited and blood samples taken for cytokine detection by commercially available Elisa kits and C-reactive protein (CRP) by laser nephelometry. Six of 11 patients with nAP died either early (n = 1) or of late septic complications. None died of iAP. The peak of cytokine and CRP level in the first 3 days of hospitalization was used for calculation. The IL-6 concentration in the blood reached up to 2600 pg/ml in the 1st few days, depending on the severity of AP, and dropped to almost zero in the next days, independently of the clinical course. The differentiation of i- versus nAP, using a cut-off line of 600 pg/ml, was correct in 20 patients [87%, sensitivity (SE): 82%, specificity (SP): 91%, P < 0.001]. The blood levels of IL-8 reached a maximum of 1381 pg/ml in the 1st few days, depending on the severity of AP, and showed a correlation with the clinical course in the following days. The peak of IL-8 blood levels indicated correctly the severity of AP in 18 out of 23 patients using a cutoff level of 200 pg/ml (accuracy: 78%, SE: 82%, SP: 75%, P < 0.01). The CRP levels increased up to a maximum of 535 mg/l and indicated the course of AP correctly in 18 out of 22 patients (SE and SP 82%, P < 0.01). There was no correlation between cytokine blood levels and mortality. In the blood samples of five patients with i- or nAP, no TNF-alpha was detectable. The blood levels of IL-6, and to a lesser extent of IL-8 and CRP, can predict the severity and early systemic complications of AP. The excessive rise in cytokines can be explained by the stimulation of immunological cells (macrophages, lymphocytes and endothelial cells) in the course of AP, inducing early systemic complications.

The effect of reperfusion on plasma tumor necrosis factor alpha and C reactive protein levels in the course of acute myocardial infarction.

Abstract: Severe acute response, the synthesis of human acute-phase proteins and the increase of plasma cytokines and adhesion molecules occur in patients in the course of acute myocardial infarction. We examined the plasma tumor necrosis factor alpha (TNF alpha), plasma creatinkinase (CK) and C-reactive protein (C-RP) levels in patients with acute myocardial infarction (AMI) in the course of 96 hours. Venous blood samples were taken at 3-hour intervals during the first 48 hours, and at 6-hour intervals during the next 48 hours. All patients were treated using thrombolytic therapy (streptokinase). Detection of the reperfusion was based on the method of measuring the time to achieve peak serum creatinkinase activity. The study was done on a group of 24 patients. Plasma levels of the parameters were compared between the group of patients with expected reperfusion versus the group of patients in which reperfusion is not suggested. The plasma TNF alpha level was elevated constantly without any significant peak. The mean plasma TNF alpha concentration was 46.8 pg/ml, SD 2.13, vs. normal level 4.35 pg/ml, p < 0.001. The plasma TNF alpha level in the group of patients with reperfused coronary artery showed a significant decrease especially during the 3rd and 4th day (the mean peak plasma TNF alpha concentration was 35.2 pg/ml, SD 15.8, vs. 66.9 pg/ml, SD 38.3 pg/ml, p < 0.005). The plasma C-RP levels were elevated throughout the time of observation in the both groups. The elevation of the plasma C-RP levels was more significant in the group of patients without successful reperfusion (80.6 mg/ml, SD 31.2, the mean plasma C-RP level of the group of the patients with successful reperfusion was 45.7 mg/ml, SD 18.1, p < 0.005). We conclude, that TNF alpha can play a role in the mechanisms of tissue injury. The successful reperfusion of coronary artery leads to significant decrease of plasma TNF alpha and C-RP levels.

[Diagnostic value of C-reactive protein levels in children with bone marrow transplantation].

Abstract: Serum quantitative C-reactive protein concentrations were measured in 16 bone marrow transplanted children at 202 occasions during and after the transplant period. Serum C-reactive protein concentrations were moderately increased in patients with viral and protozoon infections (5-67 mg/l). High values were measured in patients with bacterial and fungal infections. The C-reactive protein level was between 15-102 mg/l in Coag. neg. Staphylococcus sepsis, and 160-178 mg/l in Pseudomonas aeruginosa infection, when blood cultures were positive. Values of 154-358 mg/l was found with Candida sepsis. C-reactive protein levels were 10-17 mg/l in 7 acute GvHD episodes, only one of the patients had high level (325 mg/l) in GvHD. In these cases the condition was very severe and affected the total surface of the skin and the gastrointestinal tract also. C-reactive protein becomes a valuable aid as laboratory parameter in the diagnosis of bone marrow transplant recipients with suspected bacterial infection and in monitoring of therapeutic efficiency.