Beta2-microglobulin and cystatin C in type 2 diabetes: assessment of diabetic nephropathy.

BACKGROUND: Changes in glomerular filtration rate (GFR) provide a valuable indicator of the progression of diabetic nephropathy (DN). This study was designed to demonstrate the clinical values of serum cystatin C (Cys C) and beta2-microglobulin in the assessment of renal function in type 2 diabetics by comparing them with the GFR, estimated from the uptake phase of 99 m technetium dimetiltriamino pentaacetic acid renogram (GFR-DTPA) and creatinine clearances. MATERIALS AND METHODS: 68 type 2 diabetic patients with (urinary albumin excretions (UAE) 30 - 300 mg/24 h) (n = 39) and without (UAE < 30 mg/24 h) (n = 29) microalbuminuria and 32 controls were enrolled in the study. Serum Cys C, beta2-microglobulin, creatinine, urinary microalbumin levels, creatinine clearances and GFR-DTPA values were determined in all groups. Non-parametric ROC curves, using a cut-off GFR-DTPA of 60 mL/min/1.73 m (2), were obtained for these markers. RESULTS: Serum Cys C, beta2-microglobulin, glucose and HbA1c concentrations were significantly higher in the group with diabetes compared to controls. In the patients with microalbuminuria, serum Cys C and glucose concentrations increased significantly in comparison to patients with normoalbuminuria, while no differences were observed for beta2-microglobulin levels. Serum creatinine concentrations, GFR-DTPA values and creatinine clearances were not different between both diabetic groups and controls. Cys C was positively correlated with beta2-microglobulin and creatinine and negatively with GFR values; beta2-microglobulin was also positively correlated with serum creatinine in microalbuminurics. A significant inverse correlation was found between beta2-microglobulin and GFR values in both microalbuminurics and normoalbuminurics. CONCLUSIONS: Increased Cys C and beta2-microglobulin in diabetics may be early indicators of incipient DN. The diagnostic accuracies of Cys C and beta2-microglobulin are superior to that of serum creatinine in distinguishing between mild and moderately reduced GFR.     

检测CysC,hs-CRP和前白蛋白对老年AECOPD的临床意义

目的检测AECOPD患者CysC,hs-CRP和前白蛋白(PA)的变化,探讨其相关临床意义。方法选取2013年4月至2014年4月我院呼吸内科的老年AECOPD患者106例为观察组,经规范治疗1周,分别比较治疗前后血气分析,CysC,hs-CRP和前白蛋白水平。并选取同期稳定期COPD患者102例对照组。结果观察组治疗前与治疗后CysC,hs-CRP水平均显著高于对照组,而PA水平显著低于对照组(P0.05);观察组治疗前CysC,hs-CRP水平均显著高于治疗后,而PA水平显著低于治疗后(P0.05)。结论检测CysC,hs-CRP和前白蛋白的指标有利于临床上老年AECOPD的诊断和疗效观察。     

C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men.

BACKGROUND: There is much interest in reported associations between serum C-reactive protein and incident ischaemic heart disease. It is uncertain what this association represents. We aimed to assess the effect of confounding from a number of different sources in the Caerphilly Prospective Heart Disease Study and in particular whether the low grade inflammation indicated by C-reactive protein may be the mechanism whereby non-circulating risk factors may influence pathogenesis of ischaemic heart disease. Methods: Plasma specimens collected during 1979-83 from 1395 men with sufficient sample remaining were assayed for serum C-reactive protein by ELISA. Subsequent mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records and electrocardiographic changes at 5-yearly follow-up examinations. RESULTS: There was a positive association between C-reactive protein and incident ischaemic heart disease (P<0.005) mainly with fatal disease (P<0.002). There was also a positive association with all-cause mortality (P<0.0001). C-reactive protein was significantly associated with a number of non-circulating risk factors including body mass index (P<0.0001), smoking (P<0.0001), low forced expiratory volume in 1 s (P<0.0001), height (P=0.025), low childhood social class (P=0.014) and age (P=0.036). C-reactive protein was also associated positively with circulating risk factors including viscosity, leukocyte count, fibrinogen (all P<0.0001) and insulin (P=0.0058). After adjustment for non-circulating risk factors the association with all-incident ischaemic heart disease and ischaemic heart disease death became non-significant, but the association with all-cause mortality remained (P=0.033). Further adjustment for fibrinogen however removed any hint of an increasing trend in odds for all three outcomes. CONCLUSION: C-reactive protein levels are raised in association with a variety of established cardiovascular risk factors. Neither C-reactive protein nor the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease.     

Comorbidity assessment for mortality risk stratification in elderly patients with acute coronary syndrome

BackgroundThe Charlson's is the most used comorbidity index. It comprises 19 comorbidities, some of which are infrequent in elderly patients with acute coronary syndrome (ACS), while some others are manifestations of cardiac disease rather than comorbidities. Our goal was to simplify comorbidity assessment in elderly non-ST-segment elevation ACS patients.MethodsThe study group consisted of 1 training (n = 920, 76 ± 7 years) and 1 testing (n = 532; 84 ± 4 years) cohorts. The end-point was all-cause mortality at 1-year follow-up. Comorbidities were assessed selecting those medical disorders other than cardiac disease that were independently associated with mortality by multivariable analysis.ResultsA total of 130 (14%) patients died in the training cohort. Six comorbidities were predictive: renal failure, anemia, diabetes, peripheral artery disease, cerebrovascular disease and chronic lung disease. The increase in the number of comorbidities yielded a gradient of risk on top of well-known clinical predictors: ≥3 comorbidities (27% mortality, HR = 1.90, 95% CI 1.20–3.03, p = .006); 2 comorbidities (16% mortality, HR = 1.29, 95% CI 0.81–2.04, p = .30); and 0–1 comorbidities (7.6% mortality, reference category). The discrimination accuracy (C-statistic = 0.80) and calibration (Hosmer-Lemeshow test, p = .20) of the predictive model using the 6 comorbidities was comparable to the predictive model using the Charlson index (C-statistic = 0.80; Hosmer-Lemeshow test, p = .70). Similar results were reproduced in the testing cohort (≥3 comorbidities: 24% mortality, HR = 2.37, 95% CI 1.25–4.49, p = .008; 2 comorbidities: 14% mortality, HR = 1.59, 95% CI 0.82–3.07, p = .20; 0–1 comorbidities: 7.5% reference category).ConclusionA simplified comorbidity assessment comprising 6 comorbidities provides useful risk stratification in elderly patients with ACS.     

Multimarker approach with cystatin C,N-terminal pro-brain natriuretic peptide,C-reactive protein and red blood cell distribution width in risk stratification of patients with acute coronary syndromes

Introduction and aimBiomarkers have emerged as interesting predictors of risk in patients with acute coronary syndromes (ACS). The aim of this study was to determine the utility of the combined measurement of cystatin C (CysC), C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and red blood cell distribution width (RDW) in the risk stratification of patients with ACS.MethodsIn this prospective study including 682 patients consecutively admitted to a coronary care unit for ACS, baseline measurements of CysC, CRP, NT-proBNP and RDW were performed. Patients were categorized on the basis of the number of elevated biomarkers at presentation. The primary outcome was 6-month mortality.ResultsThe number of biomarkers elevated on admission (study score) was an independent predictor of 6-month mortality; patients with four biomarkers elevated on admission had a significantly higher risk of 6-month mortality compared with patients with none or one. In addition, in patients with high risk defined by the GRACE score, our multimarker score was able to further categorize their risk of 6-month mortality.ConclusionsA multimarker approach using CysC, NT-proBNP, CRP and RDW was an independent predictor of 6-month mortality and added prognostic information to the GRACE risk score in patients with ACS and high risk defined by GRACE, with increasing mortality in patients with a higher number of elevated biomarkers on admission.     

C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly

Serum C-reactive protein (CRP) reflects inflammation and predicts cardiovascular disease in middle-aged individuals. We investigated CRP, risk factors, and 10-year mortality in 3 elderly cohorts (aged 75, 80, and 85 years; n=455) of the population-based Helsinki Ageing Study. Clinical and laboratory examinations were performed at baseline, and in 1998, CRP was measured by a sensitive method (sensitivity 0.3 mg/L) from frozen serum samples. Mortality data were retrieved from national registers. Serum CRP ranged from 0.18 to 170.0 mg/L (interquartile range 0.68 to 4.10 mg/L, median 1.60 mg/L). CRP correlated significantly with body mass index and plasma insulin and was associated with smoking at baseline. An inverse correlation was found with albumin and total and HDL cholesterol. CRP was not associated with diabetes or cardiovascular disease but was significantly (P=0.015) higher in persons with (n=70) than without (n=385) dementia. During the 10-year follow-up, 61% (n=278) of the cohort died; half of the deaths were due to cardiovascular diseases. Mean CRP in survivors and nonsurvivors was 3.16 and 5.22 mg/L (P=0.017), respectively. After controlling for age and sex, baseline CRP (per 10 mg/L) significantly predicted the 10-year total mortality (risk ratio 1.20, 95% CI 1.08 to 1.32) and cardiovascular mortality (risk ratio 1.22, 95% CI 1.10 to 1.35). Predictive value was found in the 75-year-old cohort, but it was clearly attenuated in the 80- and 85-year-old cohorts. The results indicate that CRP is associated with several cardiovascular risk factors in the elderly. CRP alone predicts overall and cardiovascular mortality, but the prediction was significant in only the 75-year-old cohort.     

Beta 2-microglobulin levels in drug users: the influence of risk behaviour.

beta 2-microglobulin (beta 2M) levels were measured in 217 Edinburgh drug users to assess their usefulness as a marker for HIV-related disease. Eighty HIV-seronegative drug injectors had significantly higher levels than 100 HIV-seronegative blood-donor controls. Amongst 137 asymptomatic HIV-seropositive drug users, those who were defined as continued drug users had significantly higher beta 2M levels and percentages of CD3+ T lymphocytes with DR Class II expression than non-injecting drug users. beta 2M levels correlated with the percentage of activated DR+ CD3+ T lymphocytes. These findings indicate that changes in beta 2M levels may reflect differences in drug-injecting behaviour and are not influenced solely by HIV status or progression. These changes in beta 2M probably represent differing degrees of immunostimulation resulting from the antigenic challenges afforded by continued or frequent drug injection. It is important to establish normal ranges for beta 2M from HIV-seronegative controls who are matched with respect to risk group and behaviour. All these factors should be taken into account if beta 2M is to be used as a marker of HIV progression.     

C反应蛋白对不稳定型心绞痛危险分层的价值

目的：探讨C反应蛋白（CRP）对不稳定型心绞痛（UA）危险分层的临床价值。方法：对109例UA患者入院时分别测定CRP、心脏肌钙蛋白T（cTNT)、肌酸磷酸激酶同工酶（CK－MB），随访三个月，观察终点为急性心肌梗死（AMI）和心源性猝死。结果：在109例UA患者中，CRP升高37例（34.2%)，正常72例（66.1%)，三个月中发生急性心肌梗死10例，心源性猝死5例，冠状动脉成形术（PTCA）15例，冠脉搭桥术（CABG）6例。其中CRP升高组AMI的发生率明显高于正常组（P＜0.01)，但死亡率无明显差别。CRP的敏感度（83.33%)较TNT、CK－MB增高。多因素Logistic回归分析CRP升高、cTNT升高、陈旧性心梗和胸痛次数是预测近期AMI、心源性猝死的独立危险因素。结论：CRP对UA患者的近期预后和早期治疗有重要的临床价值，是危险分层的良好指标之一。     

C反应蛋白对不稳定型心绞痛危险分层的价值

目的探讨C反应蛋白(CRP)对不稳定型心绞痛(UA)危险分层的临床价值。方法对109例UA患者入院时分别测定CRP、心脏肌钙蛋白T(cTNT)、肌酸磷酸激酶同工酶(CK-MB)，随访三个月，观察终点为急性心肌梗死(AMI)和心源性猝死。结果在109例UA患者中，CRP升高37例(34.2％)，正常72例(66.1％)，三个月中发生急性心肌梗死10例，心源性猝死5例，冠状动脉成形术(PTCA)15例，冠脉搭桥术(CABG)6例。其中CRP升高组AMI的发生率明显高于正常组(P＜0.01)，但死亡率无明显差别。CRP的敏感度(83.33％)较TNT、CK-MB增高。多因素Logistic回归分析CRP升高、cTNT升高、陈旧性心梗和胸痛次数是预测近期AMI、心源性猝死的独立危险因素。结论CRP对UA患者的近期预后和早期治疗有重要的临床价值，是危险分层的良好指标之一。     

Cardiovascular disease risk stratification and comparison in a California population

This study was designed to identify the need for primary prevention of cardiovascular disease in an HMO population and to develop appropriate interventions for individuals in different risk groups, based on risk stratification and comparison. The analysis is based on a cross-sectional survey of the HMO members of a large employer group. Respondents (n=17,878) were stratified based on the Framingham model; 34% of respondents without cardiovascular disease were classified as moderate to high attributable risk for the disease, and 66% were classified as low attributable risk. Results of logistic regression analyses suggest that, compared with respondents with pre-existing cardiovascular disease, moderate- to high-risk respondents are more likely to smoke, have unhealthy diets, and be overweight, hypertensive, and hypercholesterolemic. More low-risk respondents had unhealthy diets than did those with preexisting cardiovascular disease. There were no differences between these groups for physical activity and stress. Respondents had fewer modifiable risk factors and healthier lifestyles than did those who were at risk. These findings suggest that primary prevention should be enhanced, especially among those with significantly increased risk for the disease. Moreover, the approaches of this project—population-based risk assessment, stratification, and comparison—were instrumental in identifying the target population and designing appropriate interventions.     

High-sensitivity C-reactive protein: potential adjunct for risk stratification in patients with stable congestive heart failure.

AIMS: To determine the potential adjunct of high-sensitivity (hs) C-reactive protein for risk stratification in patients with stable congestive heart failure (CHF). METHODS AND RESULTS: We studied 546 consecutive patients clinically stable with an ejection fraction <45% who were referred to our centre for evaluation of left ventricular dysfunction. hs C-reactive protein levels were determined on blood samples obtained on entry into the study. Clinical follow-up (median 972 days) was obtained for 545 patients. Cardiovascular mortality was significantly increased (P=0.001) in patients with hs C-reactive protein >3 mg/L. By multivariable analysis, including clinical, biological, and echocardiographic variables, hs C-reactive protein >3 mg/L was an independent predictor of cardiovascular mortality [HR=1.78 (1.17-2.72); P=0.008]; the strongest predictive parameter in this model was B-type natriuretic peptide (BNP) (P=0.005). When peak VO(2) was included into the model, hs C-reactive protein >3 mg/L remained an independent predictor of cardiovascular mortality [HR=1.55 (1.02-2.38); P=0.04]; the strongest predictive parameter in this model was peak VO(2) (P<0.0001). In patients with ischaemic CHF, cardiovascular mortality was significantly increased in patients with hs C-reactive protein >3 mg/L (P=0.001), whereas in patients with non-ischaemic CHF, hs C-reactive protein >3 mg/L was not associated with cardiovascular mortality (P=0.098). By multivariable analysis, hs C-reactive protein >3 mg/L was an independent predictor of cardiovascular mortality in ischaemic patients [HR=2.16 (1.23-3.78)] but not in non-ischaemic patients [HR=1.05 (0.52-2.11)]. CONCLUSION: Cardiovascular mortality is increased in CHF patients with hs C-reactive protein >3 mg/L. The impact of hs C-reactive protein is independent of usual prognostic parameters, in particular BNP and peak VO(2). The interest of hs C-reactive protein determination appears to be especially marked in patients with ischaemic cardiomyopathy.     

Beta 2-microglobulin and neopterin in patients with giardiasis

The aim of the study was to evaluate serum beta 2-microglobulin (beta-2m) and neopterin (NPT) in in patients with giardiasis. Twenty-two patients with giardiasis were examined and compared with twelve healthy subjects as a control group. Serum beta-2m and NPT concentration were determined twice: at the moment of diagnosis of giardiasis and six months after antiparasitic treatment with metronidazole. It was shown that serum beta-2m concentration in patients with giardiasis was remarkably elevated. It decreased significantly, but six months after treatment it was still higher as compared to the control group. However, serum NPT before anti-parasitic treatment was slightly lower than in the control group, but after elimination of Giardia an increase of NPT concentration above control values was observed. It is concluded that Giardia infection leads to long-lasting disturbances in the immunological status of the host and may influence macrophage function and downregulate their parasiticidal effects.     

Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly.

PURPOSE: To investigate whether interleukin-6 and C-reactive protein levels predict all-cause and cause-specific mortality in a population-based sample of nondisabled older people. SUBJECTS AND METHODS: A sample of 1,293 healthy, nondisabled participants in the Iowa 65+ Rural Health Study was followed prospectively for a mean of 4.6 years. Plasma interleukin-6 and C-reactive protein levels were measured in specimens obtained from 1987 to 1989. RESULTS: Higher interleukin-6 levels were associated with a twofold greater risk of death [relative risk (RR) for the highest quartile (> or = 3.19 pg/mL) compared with the lowest quartile of 1.9 [95% confidence interval, CI, 1.2 to 3.1]). Higher C-reactive protein levels (> or = 2.78 mg/L) were also associated with increased risk (RR = 1.6; CI, 1.0 to 2.6). Subjects with elevation of both interleukin-6 and C-reactive protein levels were 2.6 times more likely (CI, 1.6 to 4.3) to die during follow-up than those with low levels of both measurements. Similar results were found for cardiovascular and noncardiovascular causes of death, as well as when subjects were stratified by sex, smoking status, and prior cardiovascular disease, and for both early (<2.3 years) and later follow-up. Results were independent of age, sex, body mass index, and history of smoking, diabetes, and cardiovascular disease, as well as known indicators of inflammation including fibrinogen and albumin levels and white blood cell count. CONCLUSIONS: Higher circulating levels of interleukin-6 and C-reactive protein were associated with mortality in this population-based sample of healthy older persons. These measures may be useful for identification of high-risk subgroups for anti-inflammatory interventions.     

Estimation of glomerular filtration rate in the elderly: a comparison of creatinine-based formulae with serum cystatin C

OBJECTIVES: To estimate the prevalence of decreased kidney function in an elderly population and to evaluate the impact of using alternative markers of glomerular filtration rate (GFR), focusing on serum cystatin C (Cys C) and the Modification of Diet in Renal Disease (MDRD) Study prediction equation. DESIGN AND METHODS: In a cross-sectional community-based survey renal function was assessed by serum creatinine (SCreat), Cys C and GFR predicted by the Cockcroft-Gault (CG) and the MDRD Study formulae. Associations with age, gender and proteinuria were analysed by linear models. SUBJECTS: A total of 1246 elderly residents in Lieto, Finland, 64-100 years of age. RESULTS: The prevalence of moderately or severely decreased renal function, estimated by the MDRD Study equation, was 35.7%; the CG formula yielded 58.6%. The profile of Cys C performance, including variation across age groups and level of health status, showed greater similarity to GFR estimated using the MDRD Study equation than to SCreat alone, or GFR estimated using the CG formula. Discordance between high Cys C levels and only mildly decreased GFR estimates was observed in subjects with functional limitations. Microalbuminuria was associated with Cys C levels only (P =0.047). CONCLUSION: Prevalence estimates of decreased renal function amongst the elderly vary considerably depending on prediction formula used. Variation in creatinine metabolism amongst elderly comorbid patients and the critical dependence on the SCreat assay and exact calibration, make the use of creatinine-based formulae to predict GFR questionable in geriatric clinical practice. In this setting, Cys C is a promising alternative.     

C-reactive protein distribution and correlation with traditional cardiovascular risk factors in the Italian population

BackgroundC-reactive protein (CRP) increases during an inflammatory response; its plasma levels are believed to be an independent predictor of future atherosclerotic disease. We report the distribution of plasma levels of CRP and its possible relationship with other cardiovascular risk factors in an Italian cohort.MethodsCRP was assessed in frozen plasma samples of 1949 participants in the CHECK study (2001–2005), which collected clinical and biochemical data from randomly selected subjects (40–79 years) in the setting of Italian general practice.ResultsMedian CRP (interquartile range) was higher in women (1.42 [0.58–2.86] vs 1.28 [0.58–2.50]; p = .163), in people aged ≥ 65 years (1.74 [0.89–3.34] vs 1.11 [0.52–2.45]; p < .001), in patients with obesity (2.37 [1.27–4.15] vs 1.16 [0.52–2.41]; p < .001), metabolic syndrome (2.12 [1.16–3.72] vs 1.10 [0.50–2.38]; p < .001), or higher cardiovascular risk (2.03 [1.01–3.42] vs 1.19 [0.53–2.50]; p < .001). Stepwise regression analysis showed significant associations (R² = .264) of circulating log_eCRP with body mass index, fibrinogen, apoB, age, gender, smoking habits, physical inactivity, creatinine levels, and systolic blood pressure.ConclusionThis study provides epidemiological data of CRP in the Italian population and reinforces the existing evidences about the close correlation between CRP and markers of inflammation and adiposity.     

C-reactive protein and the stress tests for the risk stratification of patients recovering from unstable angina pectoris

We assessed the 90-day prognostic value of stress tests and C-reactive protein (CRP) after medical stabilization of unstable angina. We included 139 consecutive patients with unstable angina who were free of complications or did not undergo revascularization during hospitalization. Blinded CRP assays and a stress test (95 exercise electrocardiograms, 44 dobutamine echocardiograms) were performed within the first week after discharge. Of 139 participants, 44 (31.6%) had an ischemic stress test response. CRP was elevated (> 1.5 mg/dl) in 40 patients (28.7%). CRP >1.5 mg/dl was more frequently observed among patients who experienced death or myocardial infarction at 90 days (88.2% vs 20.5%, p <0.0001). Compared with the stress tests, CRP showed greater sensitivity (88% vs 47%) and specificity (81% vs 70%) for increased risk, and higher positive (37.5% vs 18.2%) and negative (98% vs 90%) predictive values. The area under the receiver operating curve of the relation with the 90-day outcome increased from 0.58 +/- 0.07 to 0.83 +/- 0.05 when the CRP data were added to the stress tests results (p <0.001). Elevation of CRP differentiated stress tests negative patients with increased risk of major events during follow-up. In patients who respond to medical treatment for unstable angina, CRP elevation may be a better parameter than the stress test in identifying the presence of persistent plaque instability.