Showing papers on "C-reactive protein published in 2003"
TL;DR: The addition of CRP to standard cholesterol evaluation may provide a simple and inexpensive method to improve global risk prediction and compliance with preventive approaches.
Abstract: In an attempt to improve global cardiovascular risk prediction, considerable interest has focused on C-reactive protein (CRP), a marker of inflammation that has been shown in multiple prospective epidemiological studies to predict incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death. CRP levels have also been shown to predict risk of both recurrent ischemia and death among those with stable and unstable angina, those undergoing percutaneous angioplasty, and those presenting to emergency rooms with acute coronary syndromes. These highly consistent clinical data are supported by abundant laboratory and experimental evidence that demonstrate that atherothrombosis, in addition to being a disease of lipid accumulation, also represents a chronic inflammatory process. In terms of clinical application, CRP seems to be a stronger predictor of cardiovascular events than LDL cholesterol, and it adds prognostic information at all levels of calculated Framingham Risk and at all levels of the metabolic syndrome. Using widely available high-sensitivity assays, CRP levels of 3 mg/L correspond to low-, moderate-, and high-risk groups for future cardiovascular events. Individuals with LDL cholesterol below 130 mg/dL who have CRP levels >3 mg/L represent a high-risk group often missed in clinical practice. The addition of CRP to standard cholesterol evaluation may thus provide a simple and inexpensive method to improve global risk prediction and compliance with preventive approaches.
Composed of five 23 kDa subunits, C-reactive protein (CRP) is an hepatically derived pentraxin that plays a key role in the innate immune response. CRP has a long plasma half-life and is now understood to be a mediator as well as a marker of atherothrombotic disease. To date, over a dozen prospective epidemiological studies carried out among individuals with no prior history of cardiovascular disease demonstrate that a single, non-fasting measure of CRP is a strong predictor …
2,369 citations
TL;DR: Low-grade systemic inflammation was present in participants with moderate to severe airflow obstruction and was associated with increased risk of cardiac injury, which may in part explain the high rates of cardiovascular complications in COPD.
Abstract: Background— Chronic obstructive pulmonary disease (COPD) increases the risk of cardiovascular disease 2- to 3-fold. The factors responsible for this association remain largely unknown. Methods and Results— We analyzed data from participants, ≥50 years of age, of the Third National Health and Nutrition Examination Survey (n=6629) to determine whether C-reactive protein (CRP) and other systemic inflammatory markers are present in participants with chronic airflow obstruction and are associated with cardiac injury. Participants with severe airflow obstruction had circulating leukocyte, platelet, and fibrinogen levels that were 460/μL (95% confidence interval [CI], 30 to 890/μL), 39 510/μL (95% CI, 21 730 to 57 290/μL), and 41.63 mg/dL (95% CI, 19.87 to 63.39 mg/dL) higher, respectively, than in those without airflow obstruction. They were also 2.18 times (95% CI, 1.46 to 3.27) more likely to have an elevated circulating CRP level. Moderate airflow obstruction was associated with smaller but still significant...
995 citations
TL;DR: Levels of CRP andIL-6 and spontaneous production of IL-6 by monocytes are elevated in patients with OSAS but are decreased by nCPAP, therefore, OSAS is associated with increased risks for cardiovascular morbidity and mortality, and n CPAP may be useful for decreasing these risks.
Abstract: Background— C-reactive protein (CRP) and interleukin (IL)-6 are important risk factors for atherosclerosis and coronary heart disease. In the present study, we examined serum levels of CRP and IL-6, IL-6 production by monocytes, and the effect of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS). Methods and Results— After polysomnography, venous blood was collected at 5 am from 30 patients with OSAS and 14 obese control subjects. Serum levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes were investigated. In addition, the effects of 1 month of nCPAP were studied in patients with moderate to severe OSAS. Levels of CRP and IL-6 were significantly higher in patients with OSAS than in obese control subjects (CRP P<0.001, IL-6 P<0.05). IL-6 production by monocytes was also higher in patients with OSAS than in obese control subjects (P<0.01). In patients with OSAS, the primary factors influencing levels of CRP were severity of OSAS and...
919 citations
TL;DR: The reciprocal association of adiponectin and CRP levels in both human plasma and adipose tissue might participate in the development of atherosclerosis.
Abstract: Background— High-sensitive C-reactive protein (hs-CRP) is a well-known risk factor for coronary artery disease (CAD). Recently, we have demonstrated that adiponectin served as an antiatherogenic plasma protein which was secreted specifically from adipocytes. The present study investigated the association between adiponectin and CRP in the blood stream and adipose tissue. Methods and Results— We studied a total of 101 male patients, 71 of whom had angiographically documented coronary atherosclerosis. As a control group, 30 patients with normal coronary angiogram were included. The plasma hs-CRP levels were negatively correlated with the plasma adiponectin levels ( r =−0.29, P r =−0.89, P Conclusions— The reciprocal association of adiponectin and CRP levels in both human plasma and adipose tissue might participate in the development of atherosclerosis.
857 citations
TL;DR: C-reactive protein levels are associated with future development of hypertension, which suggests that hypertension is in part an inflammatory disorder.
Abstract: ContextAlthough it has been hypothesized that hypertension is in part an inflammatory
disorder, clinical data linking inflammation with incident hypertension are
scarce.ObjectiveTo examine whether C-reactive protein levels, a marker of systemic inflammation,
are associated with incident hypertension.Design, Setting, and ParticipantsA prospective cohort study that began in 1992 of 20 525 female
US health professionals aged 45 years or older who provided baseline blood
samples with initially normal levels of blood pressure (BP) (systolic BP <140
mm Hg and diastolic BP <90 mm Hg, and no history of hypertension or antihypertensive
medications) and then followed up for a median of 7.8 years for the development
of incident hypertension. Plasma C-reactive protein levels were measured and
baseline coronary risk factors were collected.Main Outcome MeasureIncident hypertension, defined as either a new physician diagnosis,
the initiation of antihypertensive treatment, or self-reported systolic BP
of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg.ResultsDuring follow-up, 5365 women developed incident hypertension. In crude
models, the relative risks (RRs) and 95% confidence intervals (CIs) of developing
hypertension from the lowest (referent) to the highest levels of baseline
C-reactive protein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68),
1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend P<.001). In fully adjusted models for coronary risk
factors, the RRs and 95% CIs were 1.00, 1.07 (95% CI, 0.95-1.20), 1.17 (95%
CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and 1.52 (95% CI, 1.36-1.69) (linear
trend P<.001). C-reactive protein was significantly
associated with an increased risk of developing hypertension in all prespecified
subgroups evaluated, including those with very low levels of baseline BP,
as well as those with no traditional coronary risk factors. Similar results
were found when treating C-reactive protein as a continuous variable and controlling
for baseline BP.ConclusionC-reactive protein levels are associated with future development of
hypertension, which suggests that hypertension is in part an inflammatory
disorder.
845 citations
TL;DR: Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers and may be important mediators leading to the increased cardiovascular risk of persons with kidney disease.
Abstract: Background— Renal insufficiency has been associated with cardiovascular disease events and mortality in several prospective studies, but the mechanisms for the elevated risk are not clear. Little is known about the association of renal insufficiency with inflammatory and procoagulant markers, which are potential mediators for the cardiovascular risk of kidney disease. Methods and Results— The cross-sectional association of renal insufficiency with 8 inflammatory and procoagulant factors was evaluated using baseline data from the Cardiovascular Health Study, a population-based cohort study of 5888 subjects aged ≥65 years. C-reactive protein, fibrinogen, factor VIIc, and factor VIIIc levels were measured in nearly all participants; interleukin-6, intercellular adhesion molecule-1, plasmin-antiplasmin complex, and D-dimer levels were measured in nearly half of participants. Renal insufficiency was defined as a serum creatinine level ≥1.3 mg/dL in women and ≥1.5 mg/dL in men. Multivariate linear regression wa...
748 citations
TL;DR: It is concluded that CRP predicts future cardiovascular events in women aged 45 and above more reliably than does elevated LDL cholesterol but that screening for both of these markers may be the best policy.
Abstract: A number of prospective case-control studies have found that elevated C-reactive protein (CRP), a marker of systemic inflammation, correlates with an increased risk of myocardial infarction (MI), stroke, and sudden cardiac death. The fact that atherothrombosis frequently is not accompanied by hyperlipidemia prompted a comparison of CRP and low-density lipoprotein (LDL) cholesterol as possible predictors of an initial cardiovascular event. The study population included 27,939 generally healthy American women aged 45 and older who were taking part in the Women's Health Study, an ongoing assessment of aspirin and vitamin E for primary prevention of cardiovascular events. The women, whose mean age at baseline was 55 years, were followed up for a mean period of 8 years, noting the occurrence of MI, ischemic stroke, coronary revascularization, and cardiovascular death. One fourth of women were hypertensive, 12% were smokers, and 44% were currently using hormone replacement therapy (HRT). The relative risk of a first cardiovascular event, adjusted for age and other risk factors, correlated strongly with both CRP and LDL cholesterol. Analyzing individual components of the combined end point, which included stroke, coronary heart disease, and cardiovascular death, indicated that CRP was the better predictor of the two. The two parameters themselves were only minimally correlated with one another. Similar results were found in women currently using HRT and nonusers. More than three fourths (77%) of all events occurred in women whose LDL cholesterol was below 160 mg/dl, and close to half (46%) when the level was less than 130 mg/dl. Screening for both markers was prognostically superior to screening for either one by itself, suggesting that they identify different high-risk groups. CRP remained a strong independent predictor of cardiovascular risk after adjusting for all components of the Framingham risk score. The investigators conclude that CRP predicts future cardiovascular events in women aged 45 and above more reliably than does elevated LDL cholesterol but that screening for both of these markers may be the best policy.
523 citations
TL;DR: Results show that a low GFR per se is associated with an inflammatory state, suggesting impaired renal elimination of proinflammatory cytokines, increased generation of cytokines in uremia, or an adverse effect of inflammation on renal function.
412 citations
TL;DR: Results are in agreement with the hypothesis that the synthesis of adipose tissue TNFalpha and leptin could induce the production of interleukin-6, CRP, and other acute-phase reactants, thus contributing to the maintenance of chronic low-grade inflammation state involved in the progression of obesity and its associated comorbidities.
Abstract: BULLO ´ , MONICA, PILAR GARCIA-LORDA, ISABEL MEGIAS, AND JORDI SALAS-SALVADO ´ . Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obes Res. 2003;11:525-531. Objectives: To explore the links between tumor necrosis factor (TNF) and leptin adipose tissue expression and low-grade systemic inflammation and to determine the re- lationship between inflammation and the degree of adipos- ity, the presence of type 2 diabetes, and other cardiovascular risk factors. Research Methods and Procedures: Ninety-one women (BMI 19 to 65 kg/m 2 ) were divided into tertiles of CRP. Insulin resistance was calculated using the HOMA method. Albumin, fibrinogen, C-reactive protein (CRP), interleu- kin-6, sTNFR1, sTNFR2, and leptin levels were measured in serum and plasma samples. TNF and leptin expression were measured by reverse transcription-polymerase chain reaction in abdominal subcutaneous adipose tissue samples. Results: CRP was positively related to BMI and upper distribution of adiposity. TNF and leptin adipose tissue expression were higher in the upper tertile of CRP. Also, peripheral levels of both soluble TNFRs and leptin were higher in patients with the greatest inflammation degree. Diabetes, dislipidemia, and hypertension were most preva- lent in patients in the upper CRP tertile. Inflammatory markers of diabetic women were significantly different from those of nondiabetic women, even after adjusting for differences in body fat. BMI, type 2 diabetes, and adipose TNF mRNA levels were significant predictors of serum CRP levels (r 2 0.28, p 0.001). Discussion: These results are in agreement with the hypoth- esis that the synthesis of adipose tissue TNF and leptin could induce the production of interleukin-6, CRP, and other acute-phase reactants, thus contributing to the main- tenance of chronic low-grade inflammation state involved in the progression of obesity and its associated comorbidities.
406 citations
TL;DR: High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes and supports the value of early statin therapy in these patients.
Abstract: Background— Inflammation promotes acute coronary syndromes and ensuing clinical complications. Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina, the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown. Methods and Results— We measured C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects with unstable angina or non–Q-wave myocardial infarction were randomized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks. The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome, country, and initial level of marker. All 3 markers were markedly elevated at randomization and declined over the 16 weeks in both treatment groups. Compared with placebo, atorvastatin significantly reduced CRP, −83% (95% CI, −84%, −81%) versus −74% (95% CI, −75%, −71%) ( P P =0.0006) but not IL-6, −55% (95% CI, −57%, −53%) versus −53% (95% CI, −55%, −51%) ( P =0.3). Reductions in CRP and SAA were observed in patients with unstable angina and non–Q-wave myocardial infarction, with initial LDL cholesterol Conclusions— High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes. This supports the value of early statin therapy in these patients.
396 citations
TL;DR: Elevated IL-10 serum levels are associated with a more favorable prognosis in patients with acute coronary syndromes and elevated CRP levels, demonstrating the importance of the balance between proinflammatory and antiinflammatory markers as a major determinant of patients’ outcome in acute coronary Syndromes.
Abstract: Background— Convincing evidence suggests that atherosclerosis is an inflammatory disease. The inflammatory response is an important determinant of atherosclerotic plaque instability. Therefore, we investigated the prognostic impact of key inflammatory players, namely the inflammatory marker C-reactive protein (CRP) and the antiinflammatory cytokine interleukin-10 (IL-10), in patients with acute coronary syndromes. Methods and Results— IL-10, CRP, and troponin T were measured at baseline and before discharge in 547 patients enrolled in the placebo group of the c7E3 Anti Platelet Therapy in Unstable Refractory angina (CAPTURE) trial. Death and nonfatal myocardial infarction were recorded during 6-month follow-up. IL-10 levels did not correlate with troponin T concentrations but were inversely correlated with CRP levels (P 3.5 pg/mL; n=276) were at significantly lower risk compared with patients with elevated IL-10 levels (hazard ratio, 0.33; 95% confidence inter...
TL;DR: Interleukin-6 appeared as a risk marker of MI-coronary death, and it improved the definition of CHD risk beyond LDL cholesterol, which may reflect the underlying inflammatory reaction located in the atherosclerotic plaque.
Abstract: Objective— This study was undertaken to examine the association of plasma inflammatory markers such as C-reactive protein (CRP), interleukin-6, and fibrinogen with the incidence of coronary heart disease within the prospective cohort study on myocardial infarction (PRIME study). Methods and Results— Multiple risk factors were recorded at baseline in 9758 men aged 50 to 59 years who were free of coronary heart disease (CHD) on entry. Nested case-control comparisons were carried out on 317 participants who suffered myocardial infarction (MI)-coronary death (n=163) or angina (n=158) as an initial CHD event during a follow-up for 5 years. After adjustment for traditional risk factors, incident MI-coronary death, but not angina, was significantly associated with CRP, interleukin-6, and fibrinogen, but only interleukin-6 remained significantly associated with MI-coronary death when the 3 inflammatory markers were included in the model. The different interleukin-6 levels in Northern Ireland and France partly exp...
TL;DR: To understand CRP’s transition from an acute phase protein to a most useful inflammatory biomarker for predicting future cardiovascular events, the authors must know more about the role of the immune system in the pathogenesis of atherosclerosis.
Abstract: In a recently published prospective study comprising 28 000 women, Ridker et al1 showed that C-reactive protein (CRP) is a better predictor of the risk of cardiovascular events than low-density lipoprotein (LDL) cholesterol. The implication of this and many other supporting studies is profound and will change the way we screen and manage our patients with atherosclerosis and its associated clinical syndromes. CRP is one of the acute phase proteins that increase during systemic inflammation.2,3 Individuals without inflammation usually have CRP levels below 1 μg/mL; however, patients with bacterial infections, autoimmune diseases, and cancer frequently have CRP level as high as 100 μg/mL or even higher. It is clear that a high CRP level has no specificity in differentiating disease entities from one another. Despite its lack of specificity, CRP has now emerged as one of the most powerful predictors of cardiovascular risk. Even more remarkable, CRP’s predictive power resides in the range between 1 to 5 μg/mL, which was previously regarded to be normal in the era preceding the high-sensitivity CRP test. In fact, tests showing serum CRP levels greater than 10 μg/mL in apparently healthy men or women should be repeated to exclude occult infection or other systemic inflammatory process (see Figure). To understand CRP’s transition from an acute phase protein to a most useful inflammatory biomarker for predicting future cardiovascular events, we must know more about the role of the immune system in the pathogenesis of atherosclerosis.
CRP level and cardiovascular risk. CRP levels are listed on the left and interpretations are on the …
TL;DR: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose, and the role of some traditional risk factors, such as age and hypertension, was confirmed.
Abstract: Objective: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE).
Methods: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-s2-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed.
Results: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT.
Conclusions: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.
TL;DR: It could be shown that the majority of the studies which had investigated the role of markers for systemic inflammation, such as CRP, leukocyte count, serum fibrinogen and different cytokines, found elevated levels in patients with atherosclerosis and especially so in those with an unstable coronary disease.
TL;DR: There is now robust evidence that CRP is a strong predictor of cardiovascular risk among apparently healthy individuals, patients undergoing elective revascularization procedures, and patients presenting with ACS, and even among patients with troponin-negative ACS, elevated levels of CRP are predictive of future risk.
TL;DR: Investigating the relationship between markers of systemic inflammation and carotid atherosclerosis in patients with rheumatoid arthritis and healthy controls found a significant linear trend, consistent with hypotheses that assign a role to systemic inflammation in Atherosclerosis, and may have implications regarding RA and other chronic inflammatory diseases.
Abstract: Objective
To examine the relationship between markers of systemic inflammation and carotid atherosclerosis in patients with rheumatoid arthritis (RA) and healthy controls.
Methods
Carotid artery intima-media thickness (IMT) and carotid plaque were measured using high-resolution B-mode ultrasound in 204 patients with RA, ages 40–85, and 102 age- and sex-matched healthy persons. No subject in either group had ever smoked cigarettes. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to measure systemic inflammation. The relationship of the carotid artery IMT and carotid plaque to inflammation markers was examined, adjusting for age, sex, RA versus control status, and the cardiovascular (CV) risk factors hypercholesterolemia, systolic blood pressure, diabetes mellitus, and body mass index (BMI).
Results
A significant linear trend for increased carotid artery IMT was associated with increasing ESR and CRP categories (r = 0.16, P = 0.004 for ESR, and r = 0.13, P = 0.02 for CRP). These trends did not differ among RA cases and controls, and were independent of age, sex, and CV risk factors. The difference in carotid artery IMT between the lowest and highest categories of ESR was 0.221 mm (95% confidence interval [95% CI] 0.767–1.020, P = 0.02). The difference between extreme CRP categories was 0.275 mm (95% CI 0.039–0.509, P = 0.02). Both remained significant after CV risk factor adjustment. Carotid plaque displayed a similar relationship to markers of inflammation.
Conclusion
Increased carotid artery IMT and the presence of carotid plaque are associated with markers of systemic inflammation in patients with RA and in healthy subjects. This observation is consistent with hypotheses that assign a role to systemic inflammation in atherosclerosis, and may have implications regarding RA and other chronic inflammatory diseases.
TL;DR: Investigation of the association between C-reactive protein (CRP), the classic acute-phase protein, and incident type 2 diabetes mellitus among middle-aged men found low-grade systemic inflammation is associated with an increased risk of type 2abetes mellitus in middle- aged men.
Abstract: Background Previous studies have suggested that low-grade systemic inflammation is involved in the pathogenesis of type 2 diabetes mellitus. Objective To investigate the association between C-reactive protein (CRP), the classic acute-phase protein, and incident type 2 diabetes mellitus among middle-aged men. Methods A total of 2052 initially nondiabetic men aged 45 to 74 years who participated in 1 of the 3 MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg surveys between 1984 and 1995 were followed up for an average of 7.2 years. Incidence of diabetes was assessed by questionnaire mailed to participants in 1998. High-sensitive CRP was measured by an immunoradiometric assay. Results A total of 101 cases of incident diabetes occurred during the follow-up period. The age-standardized incidence rate was 6.9 per 1000 person-years. Men with CRP levels in the highest quartile (CRP ≥2.91 mg/L) had a 2.7 times higher risk of developing diabetes (95% confidence interval, 1.4-5.2) compared with men in the lowest quartile (CRP ≤0.67 mg/L) in a Cox proportional hazards model adjusted for age and survey. After further adjustment for body mass index, smoking, and systolic blood pressure, the observed association was significantly reduced and became nonsignificant. Conclusions Low-grade systemic inflammation is associated with an increased risk of type 2 diabetes mellitus in middle-aged men. Inflammation could be one mechanism by which known risk factors for diabetes mellitus, such as obesity, smoking, and hypertension, promote the development of diabetes mellitus.
TL;DR: CRP and blood pressure are independent determinants of cardiovascular risk, and their predictive value is additive, in prospective analyses.
Abstract: Background— Accumulating data suggest a link between blood pressure and vascular inflammation. Methods and Results— We examined the relationship between blood pressure, C-reactive protein (CRP), and incident first cardiovascular events among 15 215 women followed prospectively over a median of 8.1 years. In cross-sectional analyses at baseline, median levels of CRP for women with blood pressure <120/75, 120 to 129/75 to 84, 130 to 139/85 to 89, 140 to 159/90 to 94, and ≥160/95 mm Hg were 0.96, 1.42, 2.20, 2.82, and 3.34 mg/L, respectively (P for trend <0.0001). Increasing categories of blood pressure were significant predictors of CRP levels at baseline. In prospective analyses, both elevated CRP levels (≥3 mg/L) and increasing categories of blood pressure were independent determinants of future cardiovascular events, and CRP had incremental prognostic value at all levels of blood pressure. The adjusted hazard ratio for women with blood pressure ≥160/95 mm Hg and CRP levels ≥3 mg/L was 8.31 (95% CI, 4.44 ...
TL;DR: The findings suggest an important role for IL-6 and TNF-alpha in clinical as well as subclinical cardiovascular disease, and CRP had a weaker association with cardiovascular disease than the cytokines.
Abstract: This study investigates the association of several inflammatory markers with subclinical and clinical cardiovascular disease in older men and women. Data are from the baseline assessment of 3,045 well-functioning persons aged 70 to 79 years, participating in the Health, Aging and Body Composition study. The study sample was divided into 3 groups: "cardiovascular disease" (diagnosis of congestive heart failure, coronary artery disease, peripheral artery disease, or stroke), "subclinical cardiovascular disease" (positive findings on the Rose questionnaire for angina or claudication, ankle-brachial index <0.9, or electrocardiographic abnormalities), and "no cardiovascular disease." Serum levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, and the soluble receptors IL-6 soluble receptor, IL-2 soluble receptor, TNF soluble receptor I, and TNF soluble receptor II were assessed. Of those with IL-6 levels in the highest compared with the lowest tertile, the odds ratio (OR) for subclinical cardiovascular disease was 1.58 (95% confidence interval [CI] 1.26 to 1.97) and for clinical cardiovascular disease was 2.35 (95% CI 1.79 to 3.09). A similar association was found for TNF-alpha (OR 1.48, 95% CI 1.16 to 1.88 and OR 2.05, 95% CI 1.55 to 2.72, respectively). In adjusted analyses, CRP was not significantly associated with overall subclinical or clinical cardiovascular disease, although additional analyses did find a strong specific association between CRP and congestive heart failure (OR 1.64, 95% CI 1.11 to 2.41). Of the soluble cytokine receptors, only TNF soluble receptor I showed a significant association with clinical cardiovascular disease. Thus, our findings suggest an important role for IL-6 and TNF-alpha in clinical as well as subclinical cardiovascular disease. In this study, CRP had a weaker association with cardiovascular disease than the cytokines.
TL;DR: Increased oxidative stress and decreased antioxidant capacity may contribute to the increased risk of cardiovascular disease in women with PCOS, in addition to known risk factors such as insulin resistance, hypertension, central obesity, and dyslipidemia.
TL;DR: TNF-alpha was an independent prognostic marker for mortality in persons aged 100 years, suggesting that it has specific biological effects and is a marker of frailty in the very elderly.
TL;DR: The very early increase in concentrations of inflammatory markers after stroke may either be induced by stroke itself, or may indicate a preexisting inflammatory condition in stroke patients which may contribute to the development of stroke.
TL;DR: The presence of CRP within most atherosclerotic plaques and all acute myocardial infarction lesions, coupled with binding ofCRP to lipoproteins and its capacity for pro-inflammatory complement activation, suggests that CRP may contribute to the pathogenesis and complications of cardiovascular disease.
Abstract: The classical acute-phase protein, C-reactive protein (CRP), is an exquisitely sensitive systemic marker of disease with broad clinical utility for monitoring and differential diagnosis. Inflammation, the key regulator of CRP synthesis, plays a pivotal role in atherothrombotic cardiovascular disease. There is a powerful predictive association between raised serum CRP values and the outcome of acute coronary syndromes, and, remarkably, between even modestly increased CRP production and future atherothrombotic events in otherwise healthy individuals. Baseline CRP values also reflect metabolic states associated with atherothrombotic events. The presence of CRP within most atherosclerotic plaques and all acute myocardial infarction lesions, coupled with binding of CRP to lipoproteins and its capacity for pro-inflammatory complement activation, suggests that CRP may contribute to the pathogenesis and complications of cardiovascular disease. We review the biological properties of CRP, the association between CRP and cardiovascular disease, and the possibility that CRP may be a novel therapeutic target.
TL;DR: Low-grade inflammatory markers are associated with diabetic nephropathy in Type 1 diabetic patients and the predictive value needs to be assessed.
Abstract: Increased concentrations of C-reactive protein and interleukin-6, a finding suggestive of the presence of inflammation, have been observed in Type 2 diabetes. In such patients, C-reactive protein was predictive of diabetic nephropathy. Studies on low-grade inflammatory markers and nephropathy in Type 1 diabetic patients have shown conflicting results. Therefore we studied whether low-grade inflammation is associated with diabetic nephropathy in Type 1 diabetic patients. We divided 194 Type 1 diabetic patients into three groups from the Finnish Diabetic Nephropathy Study based upon their albumin excretion rate. Patients with normoalbuminuria (n=67) had no antihypertensive medication or signs of cardiovascular disease, while patients with microalbuminuria (n=64) or macroalbuminuria (n=63) were all treated with an angiotensin-converting enzyme inhibitor, a drug that could attenuate low-grade inflammation. As a measure of insulin sensitivity we used estimated glucose disposal rate. C-reactive protein was measured by radioimmunoassay and interleukin-6 by high sensitivity enzyme immunoassay. C-reactive protein was higher in micro- and macroalbuminuric patients compared to normoalbuminuric patients (normoalbuminuria 2.0±1.7, microalbuminuria 2.6±1.7, macroalbuminuria 2.9±2.5 mg/l; p=0.016), while interleukin-6 increased in parallel with the severity of the renal disease (1.9±1.5, 2.9±3.3, 3.6±3.1 ng/l; p<0.0001). In multiple regression analysis albumin excretion rate was the only variable independently associated with C-reactive protein (p=0.03), whereas albumin excretion rate (p=0.0003), HDL-cholesterol (p=0.0135) and duration of diabetes (p=0.0176) were independently associated with interleukin-6. Low-grade inflammatory markers are associated with diabetic nephropathy in Type 1 diabetic patients. The predictive value needs to be assessed.
TL;DR: A JUPITER trial is planned to examine the effects of rosuvastatin treatment in preventing cardiovascular events in 15,000 healthy subjects with elevated hs-CRP levels in the absence of overt hyperlipidemia.
Abstract: Inflammation is a major factor in atherothrombotic disease. Levels of high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation and a mediator of atherothrombotic disease, have been shown to correlate with cardiovascular disease risk. Recent findings in 27,939 healthy women in the Women's Health Study indicate that hs-CRP (1) is a stronger predictor of risk than low-density lipoprotein (LDL) cholesterol, (2) predicts elevated risk in subjects without overt hyperlipidemia, and (3) adds prognostic information to risk scoring and LDL cholesterol categories. Other data from this cohort show that hs-CRP level adds prognostic information to the diagnosis of the metabolic syndrome. Taken together with other data in men on the association of hs-CRP with vascular risk, a strong argument is provided for screening in the primary prevention population. With regard to potential treatment, statins have been found to reduce hs-CRP levels, and data from statin treatment trials raise the possibility that subjects with elevated hs-CRP levels may derive greater benefit from treatment than do patients without elevated hs-CRP. The Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial is planned to examine the effects of rosuvastatin treatment in preventing cardiovascular events in 15,000 healthy subjects with elevated hs-CRP levels in the absence of overt hyperlipidemia.
TL;DR: It is shown that conventional risk factors for vascular disease and endothelial adhesion molecules are important determinants of inflammation in type 1 diabetic individuals, suggesting that strategies to decrease inflammatory activity intype 1 diabetes should focus not only on control of conventional risk Factors, but also on improvement of endothelial function.
Abstract: OBJECTIVE —Inflammatory activity is increased in type 1 diabetes and may predispose to vascular disease. Its origin is not clear. We therefore investigated determinants of inflammation in type 1 diabetes. RESEARCH DESIGN AND METHODS —We performed a nested case-control study from the EURODIAB Prospective Complications Study of 543 European individuals having type 1 diabetes (278 men), diagnosed at n = 348) were those with one or more complications of diabetes; control subjects ( n = 195) were all those with no evidence of any complication. We determined levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α, combined them in a “general score of inflammatory markers,” and investigated their associations with vascular risk factors and markers of endothelial dysfunction by use of multiple linear regression analysis. RESULTS —Measures of inflammation were associated with sex, diabetes duration, glycemic control, the advanced glycation end product pentosidine, BMI, HDL cholesterol, triglycerides, and systolic blood pressure (standardized βs with the general score of inflammatory markers 0.15 [ P = 0.002], 0.15 [ P = 0.006], 0.18 [ P P = 0.005], 0.10 [ P = 0.057], −0.15 [ P = 0.001], 0.16 [ P P = 0.042], respectively). In addition, measures of inflammation were strongly associated with markers of endothelial dysfunction, soluble vascular cell adhesion molecule-1, and soluble E-selectin (standardized βs with the general score of inflammatory markers 0.28 [ P P CONCLUSIONS —We have shown that conventional risk factors for vascular disease and endothelial adhesion molecules are important determinants of inflammation in type 1 diabetic individuals, suggesting that strategies to decrease inflammatory activity in type 1 diabetes should focus not only on control of conventional risk factors, but also on improvement of endothelial function.
TL;DR: It is suggested that variation of circulating hsCRP, even within normal range, is involved in the interrelation of cardiovascular risk factors, such as age, smoking, obesity, high blood pressure and dyslipidemia, which are supposed to promote atherosclerosis and ultimately provoke cardiovascular diseases, suchAs coronary artery disease.
TL;DR: The association between CRP, body weight, and a relatively elevated creatinine clearance is a hypothesis-generating finding, suggesting that early inflammatory processes related to high body fat may predispose the kidney to glomerular hyperfiltration-related renal function loss.
TL;DR: CRP is independently associated with fasting hyperinsulinemia in nondiabetic women, providing additional support for previously reported associations between subclinical inflammation and the risk of type 2 diabetes and cardiovascular disease.
Abstract: Objective— Insulin resistance is associated with chronic subclinical inflammation, and both conditions are linked with increased risk for type 2 diabetes mellitus and atherothrombotic cardiovascular disease. Methods and Results— In a cross-sectional study conducted among participants in the Women’s Health Study, an ongoing US primary prevention trial of cardiovascular disease and cancer, we evaluated the correlates of elevated fasting insulin, a marker of insulin resistance, among 349 healthy, nondiabetic women who remained free from clinically diagnosed type 2 diabetes mellitus during a 4-year period from biomarker assessment. Fasting insulin was strongly associated with body mass index (BMI) ( r =0.53, P r =0.38, P r =0.33, P Conclusions— CRP is independently associated with fasting hyperinsulinemia in nondiabetic women. These data provide additional support for previously reported associations between subclinical inflammation and the risk of type 2 diabetes and cardiovascular disease.