Showing papers on "C-reactive protein published in 2002"
TL;DR: The data suggest that the C-reactive protein level is a stronger predictor of cardiovascular events than the LDL cholesterol level and that it adds prognostic information to that conveyed by the Framingham risk score.
Abstract: Background Both C-reactive protein and low-density lipoprotein (LDL) cholesterol levels are elevated in persons at risk for cardiovascular events. However, population-based data directly comparing these two biologic markers are not available. Methods C-reactive protein and LDL cholesterol were measured at base line in 27,939 apparently healthy American women, who were then followed for a mean of eight years for the occurrence of myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. We assessed the value of these two measurements in predicting the risk of cardiovascular events in the study population. Results Although C-reactive protein and LDL cholesterol were minimally correlated (r=0.08), base-line levels of each had a strong linear relation with the incidence of cardiovascular events. After adjustment for age, smoking status, the presence or absence of diabetes mellitus, categorical levels of blood pressure, and use or nonuse of hormone-replacement the...
3,018 citations
TL;DR: OSA is associated with elevated levels of CRP, a marker of inflammation and of cardiovascular risk, and the severity of OSA is proportional to the CRP level.
Abstract: Background—Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular and cerebrovascular disease. Inflammatory processes associated with OSA may contribute to cardiovascular morbidity in these patients. We tested the hypothesis that OSA patients have increased plasma C-reactive protein (CRP). Methods and Results—We studied 22 patients (18 males and 4 females) with newly diagnosed OSA, who were free of other diseases, had never been treated for OSA, and were taking no medications. We compared CRP measurements in these patients to measurements obtained in 20 control subjects (15 males and 5 females) who were matched for age and body mass index, and in whom occult OSA was excluded. Plasma CRP levels were significantly higher in patients with OSA than in controls (median [range] 0.33 [0.09 to 2.73] versus 0.09 [0.02 to 0.9] mg/dL, P0.0003). In multivariate analysis, CRP levels were independently associated with OSA severity (F6.8, P0.032). Conclusions—OSA is associated with elevated levels of CRP, a marker of inflammation and of cardiovascular risk. The severity of OSA is proportional to the CRP level. (Circulation. 2002;105:2462-2464.)
911 citations
TL;DR: Rosiglitazone reduces serum levels of MMP-9 and the proinflammatory marker CRP in patients with type 2 diabetes, which indicates potentially beneficial effects on overall cardiovascular risk.
Abstract: Background— Markers of systemic inflammation (eg, C-reactive protein [CRP] and interleukin-6 [IL-6]) have been proposed to be “nontraditional” risk factors for cardiovascular disease in patients with type 2 diabetes mellitus. Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of atherosclerotic plaque rupture, which raises the possibility of the use of MMP-9 levels as a marker for future myocardial infarction or unstable angina. In vitro and animal studies suggest that thiazolidinediones can reduce the expression of these markers. The purpose of this analysis was to determine whether rosiglitazone alters serum concentrations of CRP, IL-6, MMP-9, and white blood cell count (WBC) and to examine the relationship of these effects with demographic and disease variables. Methods and Results— CRP, IL-6, MMP-9, and WBC were analyzed from stored frozen serum samples obtained from patients with type 2 diabetes who completed a 26-week randomized, double-blind, placebo-controlled study. After ...
881 citations
TL;DR: Observations about C-reactive protein add to the notion that low-grade inflammation is important in the pathogenesis of type 2 diabetes, and have clinical potential in helping to better predict individuals destined to develop type 1 diabetes.
Abstract: Accumulating evidence implicates inflammation as a potential pathway in the pathogenesis of type 2 diabetes. The objective of the present study was to assess the ability of C-reactive protein (CRP) to predict the development of diabetes in middle-aged men in the West of Scotland Coronary Prevention Study. Baseline plasma samples for CRP measurement were available for 5,245 men of whom 127 were classified as having a transition from normal glucose control to overt diabetes during the study, based on American Diabetes Association criteria. Baseline CRP was an important predictor of the development of diabetes in univariate analysis (hazard ratio [HR] for an increase of 1 SD = 1.55; 95% CI 1.32–1.82; P 4.18 mg/l) was associated with a greater than threefold risk of developing diabetes (HR 3.07; 95% CI 1.33–7.10) in a multivariate analysis at 5 years. Thus, CRP predicts the development of type 2 diabetes in middle-aged men independently of established risk factors. Because CRP, the most commonly used acute-phase protein in clinical practice, is very stable in serum, our observations have clinical potential in helping to better predict individuals destined to develop type 2 diabetes. They also add to the notion that low-grade inflammation is important in the pathogenesis of type 2 diabetes.
728 citations
TL;DR: Inflammatory bio‐markers and cardiovascular risk prediction (Review).
Abstract: . Blake GJ, Ridker PM (Harvard Medical School, Boston, MA, USA). Inflammatory bio-markers and cardiovascular risk prediction (Review). J Intern Med 2002; 252: 283–294.
Inflammatory processes are now recognized to play a central role in the pathogenesis of atherosclerosis and its complications. Plasma levels of several markers of inflammation have been found to be associated with future cardiovascular risk in a variety of clinical settings. These markers include cell adhesion molecules, cytokines, pro-atherogenic enzymes and C-reactive protein (CRP). Initially thought of as an inactive downstream marker of the inflammatory cascade, emerging evidence suggests that CRP may be directly involved in atherogenesis, and that arterial plaque can produce CRP, independent of traditional hepatic pathways. In addition to being a strong predictor of future cardiovascular risk amongst patients presenting with acute coronary syndromes, numerous studies have found that baseline levels of CRP are associated with risk of future myocardial infarction, stroke, peripheral vascular disease and cardiovascular death amongst apparently healthy populations. The combination of measurement of a marker of inflammation with lipid testing may improve upon risk stratification based on lipid testing alone, and intensification of programmes for exercise, weight loss, and smoking cessation is recommended for those with elevated CRP levels. Further trials are needed to confirm the potential benefits of statins amongst individuals with elevated CRP levels.
711 citations
TL;DR: The view that inflammatory markers may reflect not only peripheral disease, but also cerebral disease mechanisms related to dementia, and that these processes are measurable long before clinical symptoms appear, is supported.
Abstract: Inflammatory responses are associated with cardiovascular disease and may be associated with dementing disease. We evaluated the long-term prospective association between dementia and high-sensitivity C-reactive protein, a nonspecific marker of inflammation. Data are from the cohort of Japanese American men who were seen in the second examination of the Honolulu Heart Program (1968-1970) and subsequently were reexamined 25 years later for dementia in the Honolulu-Asia Aging Study (1991-1996). In a random subsample of 1,050 Honolulu-Asia Aging Study cases and noncases, high-sensitivity C-reactive protein concentrations were measured from serum taken at the second examination; dementia was assessed in a clinical examination that included neuroimaging and neuropsychological testing and was evaluated using international criteria. Compared with men in the lowest quartile (<0.34mg/L) of high-sensitivity C-reactive protein, men in the upper three quartiles had a 3-fold significantly increased risk for all dementias combined, Alzheimer's disease, and vascular dementia. For vascular dementia, the risk increased with increasing quartile. These relations were independent of cardiovascular risk factors and disease. These data support the view that inflammatory markers may reflect not only peripheral disease, but also cerebral disease mechanisms related to dementia, and that these processes are measurable long before clinical symptoms appear.
666 citations
TL;DR: Leisure-time physical activity was positively associated with serum albumin concentration and inversely associated with both log-transformed plasma fibrinogen concentration and log- transformed white blood cell count, adding to mounting evidence that physical activity may reduce inflammation.
Abstract: Background: Physical activity may lower the risk for coronary heart disease by mitigating inflammation, which plays a key role in the pathophysiology of atherosclerosis. The purpose of this study was to examine the association between physical activity and C-reactive protein concentration in a national sample of the U.S. population.
Methods: The analytic sample included 13,748 participants >or=20 years of age in the National Health and Nutrition Examination Survey III (1988-1994) with complete data for the main study variables.
Results: After adjusting for age, sex, ethnicity, education, work status, smoking status, cotinine concentration, hypertension, body mass index, waist-to-hip ratio, high-density lipoprotein cholesterol concentration, and aspirin use, the odds ratios for elevated C-reactive protein concentration (dichotomized at the >or=85th percentile of the sex-specific distribution) were 0.98 (95% confidence interval = 0.78-1.23), 0.85 (0.70-1.02), and 0.53 (0.40-0.71) for participants who engaged in light, moderate, and vigorous physical activity, respectively, during the previous month compared with participants who did not engage in any leisure-time physical activity. In addition, leisure-time physical activity was positively associated with serum albumin concentration and inversely associated with both log-transformed plasma fibrinogen concentration and log-transformed white blood cell count.
Conclusions: These results add to mounting evidence that physical activity may reduce inflammation, which is a critical process in the pathogenesis of cardiovascular disease.
593 citations
TL;DR: The results suggest that the association between physical activity and reduced coronary heart disease risk may be mediated by anti-inflammatory effects of regular physical activity.
Abstract: Background: Physical activity has been associated with a reduced risk of coronary heart disease, but the mechanism underlying this association is unclear. Because coronary heart disease is increasingly seen as an inflammatory process, it might be reasonable to hypothesize that physical activity reduces risk of coronary heart disease by reducing or preventing inflammation. Methods: The study examined the relationship between physical activity and elevated inflammation as indicated by a high C-reactive protein level, white blood cell count, or fibrinogen level. Study subjects were 3638 apparently healthy US men and women 40 years and older who participated in the Third National Health and Nutrition Examination Survey. Results: More frequent physical activity was independently associated with a lower odds of having an elevated C-reactive protein level. Compared with those engaging in physical activity 0 to 3 times per month, the odds of having an elevated C-reactive protein level was reduced among those engaging in physical activity 4 to 21 times per month (odds ratio, 0.77; 95% confidence interval, 0.58-1.02) and 22 or more times per month (odds ratio, 0.63; 95% confidence interval, 0.43-0.93) (P for trend, .02). Similar associations were seen for white blood cell count and fibrinogen levels. Conclusions: More frequent physical activity is independently associated with a lower odds of having elevated inflammation levels among apparently healthy US adults 40 years and older, independent of several confounding factors. The results suggest that the association between physical activity and reduced coronary heart disease risk may be mediated by anti-inflammatory effects of regular physical activity. Arch Intern Med. 2002;162:1286-1292
545 citations
TL;DR: P levels may be useful in identifying apparently healthy men who are at an increased long-term risk of SCD, according to a prospective, nested, case-control analysis involving 97 cases ofSCD among apparentlyhealthy men enrolled in the Physician’s Health Study.
Abstract: Background— Sudden cardiac death (SCD) is an important cause of mortality even among apparently healthy populations. However, our ability to identify those at risk for SCD in the general population is poor, and more specific markers are needed. Methods and Results— To compare and contrast the relative importance of C-reactive protein (CRP), homocysteine, and lipids as long-term predictors of SCD, we performed a prospective, nested, case-control analysis involving 97 cases of SCD among apparently healthy men enrolled in the Physician’s Health Study. Of these plasma markers measured, only baseline CRP levels were significantly associated with the risk of SCD over the ensuing 17 years of follow-up (P for trend=0.001). The increase in risk associated with CRP levels was primarily seen among men in the highest quartile, who were at a 2.78-fold increased risk of SCD (95% CI 1.35 to 5.72) compared with men in the lowest quartile. These results were not significantly altered in analyses that (in addition to the m...
544 citations
TL;DR: Interleukin-6 and C-reactive protein are markers of systemic vascular inflammation that herald atherothrombosis and may have important interrelationships with traditional cardiovascular risk factors in women.
Abstract: Objective— Interleukin-6 (IL-6) and C-reactive protein (CRP) are markers of systemic vascular inflammation that herald atherothrombosis and may have important interrelationships with traditional cardiovascular risk factors. Methods and Results— We conducted a cross-sectional analysis among 340 apparently healthy women enrolled in the Women’s Health Study. In unadjusted analyses, higher levels of IL-6 and CRP were seen with increasing body mass index (BMI), systolic and diastolic blood pressure, and smoking exposure. IL-6 levels were related to the frequency of alcohol intake (P=0.002) and showed an inverse relationship with exercise frequency and hormone replacement therapy (P<0.0001 for both). CRP levels increased with hormone replacement therapy (P=0.0002). Associations among IL-6, CRP, and lipid levels were minimal. Overall, mean levels of IL-6 and CRP increased with increasing numbers of clinical risk factors (P<0.0001). In multivariate analyses, independent relationships were seen between levels of I...
458 citations
TL;DR: In this article, the authors examined associations of depressive symptoms with inflammation and coagulation factors in persons aged > 65 years, and found that depression was associated with elevated C-reactive protein (CRP), white blood cell (WBC) count, total platelet count, and albumin.
Abstract: Depression is associated with increased cardiovascular disease, but the underlying mechanisms are not well understood. This study examines associations of depressive symptoms with inflammation and coagulation factors in persons aged > 65 years. Blood samples were obtained from 4,268 subjects free of cardiovascular disease (age 72.4 +/- 5.5 years, 2,623 women). Inflammation markers were C-reactive protein (CRP), white blood cell (WBC) count, total platelet count, and albumin; coagulation factors included factors VIIc and VIIIc and fibrinogen. Depression was assessed with the Center for Epidemiologic Studies Depression scale, and states of energy depletion with a validated exhaustion index. Statistical adjustments were made for risk factors (age, sex, race, systolic blood pressure, smoking status, diabetes mellitus) and physical measures of frailty (isometric handgrip, timed 15-feet walk test, activity level). Depression was associated with elevated CRP (3.31 +/- 0.10 vs 3.51 +/- 0.21 mg/L), WBC (6.14 +/- 0.03 vs 6.43 +/- 0.11 10(6)/L), fibrinogen (319 +/- 1 vs 326 +/- 3 mg/dl), and factor VIIc (124.6 +/- 0.6% vs 127.2 +/- 1.3%; all p 65 years.
TL;DR: C-reactive protein is a nonspecific but sensitive marker of inflammation and its role as a predictor of survival has been shown in multiple myeloma, melanoma, lymphoma, ovarian, renal, pancreatic, and gastrointestinal tumors.
Abstract: C-reactive protein (CRP) is a nonspecific but sensitive marker of inflammation. Interleukin-6 (IL-6), IL-1, and tumor necrosis factor a induce the synthesis of CRP in hepatocytes. Increased CRP level is considered to be an important risk factor for atherosclerosis, myocardial infarction, peripheral vascular disease, and ischemic stroke. It is positively correlated with weight loss, anorexiacachexia syndrome, extent of disease, and recurrence in advanced cancer. Its role as a predictor of survival has been shown in multiple myeloma, melanoma, lymphoma, ovarian, renal, pancreatic, and gastrointestinal tumors. Measurement of CRP is simple, cheap, and routine and provides valuable information in palliative care.
TL;DR: The results suggest that PTX3 may contribute to the pathogenesis of atherosclerosis and is investigated in atherosclerotic lesions.
Abstract: Elevated plasma levels of the pentraxin protein family member C-reactive protein (CRP) are associated with increased risk of cardiovascular disease in both healthy and high-risk subjects. The long pentraxin family member, pentraxin 3 (PTX3), was recently described. Like CRP, PTX3 is induced by acute inflammatory stimuli and is increased in the blood of patients with acute myocardial infarction. Unlike CRP, it is expressed in a wide range of cell types, but not in hepatocytes. In this study, we have investigated the expression of PTX3 in atherosclerosis. Immunohistochemical staining of advanced atherosclerotic lesions revealed strong expression of PTX3. In contrast, no PTX3 expression was observed in nonatherosclerotic internal mammary arteries. By staining serial sections with cell type– and PTX3-specific antibodies, we observed that PTX3 was produced principally by macrophages and endothelial cells. Infrequent expression by smooth muscle cells was also observed. Our results suggest that PTX3 may contribute to the pathogenesis of atherosclerosis.
TL;DR: Although the −174C allele was not associated with incident events, associations of the genotype with inflammation and MRI infarcts, combined with the plasma IL-6 results, suggest that IL- 6 may chronically predispose an individual to develop atherosclerosis.
Abstract: Objective— Interleukin (IL)-6–mediated inflammation is involved in cardiovascular disease (CVD) We assessed IL-6 levels and the −174G>C genotype in a case-control study of men and women (average age 73 years) within the Cardiovascular Health Study Methods and Results— Cases included incident angina, myocardial infarction (MI), and stroke (5-year follow-up), prevalent MI, and MRI-detectable infarcts A control group and a group free of subclinical CVD were used for comparison The −174C allele was associated with higher C-reactive protein (11% higher, P =002), fibrinogen (3% higher, P =002), and IL-6 (5% higher; P =016) IL-6 was associated with increased atherosclerosis when the control group was compared with the group free of subclinical CVD No further association with CVD events was found when case groups were compared with the control group Compared with its absence, presence of the −174C allele was associated with risk of MRI infarcts (odds ratio 15) Conclusions— IL-6 levels differentiated those with subclinical CVD from those without Although the −174C allele was not associated with incident events, associations of the genotype with inflammation and MRI infarcts, combined with the plasma IL-6 results, suggest that IL-6 may chronically predispose an individual to develop atherosclerosis
TL;DR: A positive clinical response to infliximab was associated with a higher CRP level before treatment in the population of Crohn disease patients, but there was no relevant association with -308 TNF gene polymorphism.
Abstract: Background: Two-thirds to three-fourths of patients with either refractory luminal or fistulizing Crohn disease respond to infliximab treatment. The ability or inability to respond seems to persist over time. Biological characteristics and/or genetic background can influence the response to treatment. The aim was to assess the value of C-reactive protein and TNF-2 serum levels before treatment as well as the TNF -308 gene polymorphism in the prediction of response to infliximab treatment in Crohn disease. Methods: Two-hundredand-twenty-six Crohn disease patients treated in the setting of an expanded access programme to infliximab in Belgium were studied. There were 136 refractory luminal diseases and 90 refractory fistulizing diseases. Luminal diseases were treated with one single infusion; fistulizing diseases with three infusions at weeks 0,2 and 6. A clinical response to treatment was defined as either a Crohn disease activity index 5 mg/l) than in patients with a normal CRP value (<5mg/l) before treatment (76% versus 46%; P = 0.004; OR: 0.26 (0.11-0.63)). Allelic and genotype frequencies for -308 TNF gene polymorphism were not significantly different between responders and non-responders - with the exception of a slightly higher TNF2 frequency in non-responders in luminal disease (22.1 % versus 11.6%; P = 0.04). However, this was not associated with a significant difference in genotype frequencies. Conclusion: A positive clinical response to infliximab was associated with a higher CRP level before treatment in our population of Crohn disease patients, but there was no relevant association with -308 TNF gene polymorphism. We therefore suggest that CRP level may help to identify better candidates for infliximab treatment.
TL;DR: A single determination of CRP is a powerful indicator of all cause and cardiovascular death even after a follow-up period of 4 years in patients on hemodialysis treatment.
TL;DR: C-reactive protein is a moderately strong marker of risk of CHD in this cohort of middle-aged adults, consistent with the role of inflammation in the pathogenesis of coronary heart disease events.
TL;DR: The CRP level measured within 12 hours after symptom onset of an acute ischemic stroke is not independently related to long-term prognosis, and a CRP increase between 12 and 24 hours after symptoms onset predicts an unfavorable outcome and is associated with an increased incidence of cerebrovascular and cardiovascular events.
Abstract: Background and Purpose— Recent studies described an association between elevated levels of C-reactive protein (CRP) and outcome after ischemic stroke. We investigated the impact of early serial CRP...
TL;DR: Participants without diabetes and those at intermediate risk may benefit from risk stratification based on high-sensitivity CRP levels and CAC, because both factors contribute independently toward the incidence of cardiovascular events.
Abstract: Background— The South Bay Heart Watch is a prospective cohort study designed to appraise the value of coronary calcium and risk factors for predicting outcomes in asymptomatic adults. Two factors that may be related to subsequent cardiovascular events are coronary calcium (CAC, a manifestation of subclinical atherosclerosis) and high-sensitivity C-reactive protein (CRP, a measure of chronic inflammation). Methods and Results— Between December 1990 and December 1992, 1461 participants without coronary heart disease underwent baseline risk factor screening, computed tomography for CAC, and measurement of CRP. Participants were followed up for 6.4±1.3 years. Cox regression analyses were conducted for the 967 nondiabetics with CRP levels ≤10 mg/L to estimate the risk-factor–adjusted relative risks of CAC and CRP for the occurrence of (1) nonfatal myocardial infarction (MI) or coronary death and (2) any cardiovascular event (MI, coronary death, coronary revascularization, or stroke). CAC was a predictor of bot...
TL;DR: Plasma CRP concentrations were significantly reduced among carriers of a 1059G/C polymorphism in the human CRP gene (GC or CC) as compared with non-carriers, suggesting that genetic and environmental determinants each importantly contribute to the vascular risk associated with inflammation.
TL;DR: As inflamed female patients have a better outcome that inflamed males the present observation suggests that sex hormones may have important cardioprotective effects that limit the effect of inflammation on vascular injury in female ESRD patients.
TL;DR: Platelet, ferritin, and albumin responses are not part of the significant APR seen during short lived attacks of FMF, and inflammation continues in about two thirds of the patients during an attack-free period.
Abstract: Objective: To test the hypothesis that not all acute phase reactants respond in the same way during attacks of familial Mediterranean fever (FMF) and that there is a subclinical acute phase response (APR) in a proportion of patients during the interval between attacks. Methods: Blood and urine samples were obtained from 49 patients with FMF during an attack and the attack-free period that followed, to test for erythrocyte sedimentation rate, C reactive protein (CRP), fibrinogen, white blood cell count, platelet count, factor VIII related antigen, haptoglobin, protein electrophoresis, ferritin, proteinuria, and haematuria. Control groups comprised 29 patients with juvenile idiopathic arthritis, 10 patients with various infectious diseases, and 19 healthy subjects. Results: A marked APR was seen during the FMF attacks which was comparable with that obtained in the diseased control groups. CRP was the only acute phase protein that was raised during all attacks. Neither thrombocytosis nor an increase in ferritin levels (except one) was noted in any attack. Serum albumin levels remained unchanged. In two thirds of the patients with FMF a continuing APR was seen in between the attacks. Conclusion: Platelet, ferritin, and albumin responses are not part of the significant APR seen during short lived attacks of FMF, and inflammation continues in about two thirds of the patients during an attack-free period.
01 Jan 2002
TL;DR: C-reactive protein correlates with extent of CAD, but the degree of correlation is low, and Severity/extent of CAD and CRP are independent and additive predictors of risk.
Abstract: OBJECTIVES The objective of this study was to determine the prognostic value of C-reactive protein (CRP)independent of coronary angiographic findings.BACKGROUND High sensitivity CRP, a marker of inflammation, predicts risk of cardiovascular events.However, it is uncertain whether it remains predictive once angiographic findings areconsidered.METHODS A total of 2,554 patients with angina but without acute myocardial infarction (MI) werestudied angiographically; 1,848 patients had coronary artery disease (CAD) and 706 patientsdid not. Coronary artery disease was quantified in five ways and combined for a CAD score.C-reactive protein was measured and patients were followed for up to five years for death orMI.RESULTS C-reactive protein correlated with the extent of CAD, but correlation coefficients were low(0.02 to 0.08). Of angiographic measures, the CAD score best predicted future events (hazardratio [HR] 1.8 [1.2 to 2.6], p 0.004, for CAD score 4). C-reactive protein 1.0 mg/dlwas predictive in both patients without CAD (HR 2.3 [0.9 to 5.5], p 0.07) and withCAD (HR 2.1 [1.5 to 3.1], p 0.0001). Multivariate adjustment resulted in little changein HR. C-reactive protein retained predictive value within each quintile of CAD score.C-reactive protein and CAD independently and additively contributed to the risk prediction:low CRP and lowest CAD score was associated with lowest risk, and high CRP and highestCAD score was associated with the highest risk, with a 10-fold difference between extremes(2.5% vs. 24%).CONCLUSIONS C-reactive protein correlates with extent of CAD, but the degree of correlation is low.Severity/extent of CAD and CRP are independent and additive predictors of risk. Therapyshould target CRP-associated risk as well as angiographically evident stenosis. (J Am CollCardiol 2002;39:632–7) © 2002 by the American College of Cardiology
TL;DR: In this article, the prognostic value of C-reactive protein (CRP) independent of coronary angiographic findings was determined for predicting risk of cardiovascular events in 2,554 patients with angina but without acute myocardial infarction (MI) were studied angiographically.
TL;DR: The reduction in cytochrome P450 3A function with acute-phase reaction was independent of the tumour type and C-reactive protein elevation was associated with poor performance status, which indicates that the sub-group of cancer patients with significant acute- phase response have compromised drug metabolism, which may have implications for the safety of chemotherapy in this population.
Abstract: Inflammatory disease states (infection, arthritis) are associated with reduced drug oxidation by the cytochrome P450 3A system. Many chemotherapy agents are metabolised through this pathway, and disease may therefore influence inter-individual differences in drug pharmacokinetics. The purpose of this study was to assess cytochrome P450 3A function in patients with advanced cancer, and its relation to the acute-phase response. We evaluated hepatic cytochrome P450 3A function in 40 patients with advanced cancer using the erythromycin breath test. Both the traditional C(20min) measure and the recently proposed 1/T(MAX) values were estimated. The marker of acute-phase response, C-reactive protein and the pro-inflammatory cytokines IL-6, IL-1beta, TNFalpha and IL-8 were measured in serum or plasma at baseline. Cancer patients with an acute phase response (C-reactive protein >10 mg x l(-1), n=26) had reduced metabolism as measured with the erythromycin breath test 1/T(MAX) (Kruskal-Wallis Anova, P=0.0062) as compared to controls (C-reactive protein < or =10 mg x l(-1), n=14) Indeed, metabolism was significantly associated with C-reactive protein over the whole concentration range of this acute-phase marker (r=-0.64, Spearman Rank Correlation, P<0.00001). C-reactive protein serum levels were significantly correlated with those of IL-6 (Spearman coefficient=0.58, P<0.0003). The reduction in cytochrome P450 3A function with acute-phase reaction was independent of the tumour type and C-reactive protein elevation was associated with poor performance status. This indicates that the sub-group of cancer patients with significant acute-phase response have compromised drug metabolism, which may have implications for the safety of chemotherapy in this population.
TL;DR: It is speculated that in patients undergoing weight loss by surgical measures the marked reduction in C-reactive protein might be beneficial in reducing their cardiovascular risk and is not solely mediated by IL-6 and TNF-α.
Abstract: Background: Human adipose tissue expresses and releases proinflammatory cytokines and these measures of chronic inflammation have recently been associated with obesity. Hypothesis: To test whether the proinflammatory state is reversible in subjects undergoing weight loss by surgical measures. Subjects and Methods: Twenty morbidly obese women participated in this prospective study. Subjects were examined for fat mass, high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) before and 1 y after Swedish adjustable gastric banding. Results: Anthropometric measures displayed a significant reduction of the body mass index (BMI) from 41.6±5.4 to 30.8±6.1 kg/m2 and the fat mass from 53.9±10.3 to 29.8±12.1 kg (mean±s.d.). Hs-CRP levels decreased significantly from 1.33±1.21 mg/dl in pre-gastric banding subjects to 0.40±0.61 mg/dl in post-gastric banding subjects, respectively. IL-6 and TNF-α levels did not differ significantly between pre- and post-gastric banding subjects. Conclusions: We speculate that in these patients the marked reduction in C-reactive protein might be beneficial in reducing their cardiovascular risk and is not solely mediated by IL-6 and TNF-α.
TL;DR: Elevated levels of CRP, more than of D-dimer and fibrinogen, are related to the risk of new cardiovascular events after ischemic stroke, and the efficacy of antiplatelet therapy in secondary prevention appears to be directly related to level of inflammatory and thrombotic markers.
Abstract: Background and Purpose— The measurement of markers of inflammation or thrombosis has been proposed as a method to improve the prediction of risk in patients with vascular disease. We evaluated the usefulness of these markers as predictors of cardiovascular events in ischemic stroke patients. Methods— We analyzed levels of C-reactive protein (CRP), fibrinogen, and D-dimer within the first 24 hours after stroke onset in 473 first-ever ischemic stroke patients and determined the cumulative survival curves free of cardiovascular events in relation to the level of each of these markers according to the Kaplan-Meier method. We adjusted for possible confounding variables using a multivariate Cox proportional-hazards model. Results— Patients in the highest tertiles of D-dimer, fibrinogen, and CRP were associated with an excess risk of new cardiovascular events of 36% (P=0.0134), 63% (P<0.0001), and 72% (P<0.0001), respectively, compared with patients in the lowest tertile. The patients in the highest tertile of C...
TL;DR: Findings suggest that in clinically healthy men, atherosclerosis could have origins more closely linked with inflammation than with other processes, and in clinicallyhealthy men, the odds of an MI are higher with increasing levels of CRP.
TL;DR: The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators and changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.
Abstract: Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, α1-acid-glycoprotein (AAG), α1-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.
TL;DR: The hypothesis that subjects with low IL-10 production levels have an increased risk of stroke is supported.
Abstract: Background— Experimental evidence indicates that interleukin-10 (IL-10) deficiency is associated with the development of cardiovascular and cerebrovascular disease. We analyzed the relation between low IL-10 production levels, history of stroke, and incident fatal stroke. Summary of Report— All 85-year-old inhabitants of Leiden, Netherlands (n=599) were visited at their place of residence (response rate, 87%). Production levels of the anti-inflammatory cytokine IL-10 were assessed in a whole blood assay whereby lipopolysaccharide was used as a stimulus. Plasma concentrations of C-reactive protein (CRP) were also used as a marker of inflammation. A history of stroke was obtained at baseline (prevalence, 10%). The number of fatal strokes was prospectively obtained for a median follow-up of 2.6 years (incidence, 1.82 per 100 person-years at risk). Subjects with a history of stroke had significantly lower median IL-10 production levels at baseline than subjects without stroke (558 versus 764 pg/mL; P<0.05). T...