Predictors Of C-reactive Protein Research Articles

A study to assess the predictive value of CRP in detecting type-II diabetes mellitus with nephropathy

To assess C reactive protein (CRP) in detecting type-II diabetes mellitus with nephropathy. Patients with a history of diabetes type 2 with nephropathy and patients with diabetes type 2 without nephropathy were included in the study. A total of 30 cases, both male and female, were recruited and compared with30 normal healthy adults. Each participant (age, gender, BMI, i.e. body mass index and WHR, i.e. waist-hip ratio) were recorded. CRP was measured by immunoturbidimetric method. Total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol were measured by the CHOD-POD method, GPO-PAP method, and CHOD-POD/phosphotungstic method. Low-density lipoprotein (LDL)cholesterol and very low-density cholesterol were measured by Friedewald formula. Lipoprotein ratios ware also calculated. CRP was significantly (p=0.0001) higher among cases (12.60±3.30) compared to controls (5.47±4.29). CRP >9.5 correctly (efficacy) predicted DM2 with DN among 46.7% cases with sensitivity and specificity of 93.3 (95%CI=84.4-102.3) and 76.7 (95%CI=61.5-91.8) respectively. The area under the curve (AUC) was also high (AUC=0.85, 95%CI=0.75-0.95). There was a poor correlation of CRP with lipid profile among DM-2 with DN. Linear regression analysis showed that lipid biomarkers such as HDL, LDL, VLDL & total cholestarol-to-HDL ratio as well as BMI and WHR were positive predictors of CRP after adjusted for age and sex. In turn, HDL, LDL, VLDL and TC to HDL ratio level were a negative predictive factor of CRP levels. The increase of 1 unit on HDL was associated with a reduction of 1.25 in CRP levels. However, all the predictors had no statistical significance (p>0.05). In this study, the level of CRP was higher among cases compared to controls. This study also found that CRP >9.5 had good sensitivity and specificity in predicting DM2 with DN.

Abstract B21: C-reactive protein and ovarian cancer risk in the Ovarian Cancer Cohort Consortium

Abstract Background: C-reactive protein (CRP), a general marker of inflammation, has been consistently associated with increased ovarian cancer risk. However, few studies have had the ability to evaluate differences in association by ovarian tumor subtype. Thus, we leveraged previously measured CRP levels in prediagnostic specimens from 6 studies in the Ovarian Cancer Cohort Consortium (OC3). Methods: We pooled data on CRP and ovarian cancer risk among nested case-control studies conducted in CLUEII, EPIC, NHS, NHSII, NYUWHS, and PLCO; invasive ovarian cancer cases were matched to one or two controls on age, menopausal status, hormone therapy (HT) use, and fasting status. Due to variability in CRP distributions across studies in part due to different assays, we regressed CRP levels on study (with EPIC as the reference), adjusting for predictors of CRP, including age, menopause/HT status, fasting status, BMI, aspirin use, and smoking. Levels for each study (except EPIC) were recalibrated based on the beta coefficient for that study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for natural log-transformed CRP (continuous), quartiles (based on control distributions) and clinical cutpoints (<1, 1-<10, ≥10mg/L) using conditional logistic regression, which implicitly accounts for matching factors. We examined associations for all invasive cancer and by histotype (serous [n=740], endometrioid [n=109], mucinous [n=69], clear cell [n=47]). Primary analyses (model 1) adjusted for reproductive risk factors (oral contraceptive use, number of pregnancies, and tubal ligation); model 2 additionally adjusted for known predictors of CRP, including BMI, smoking, and aspirin use, that also may be related to ovarian cancer risk. Results: There was a marginally significant linear association between CRP and total invasive ovarian cancer risk among 1,135 cases and 2,124 controls (p-trend=0.05), which was slightly attenuated when adjusting for BMI, smoking, and aspirin use (p-trend=0.08). The model 1 OR (95% CI) was 1.24 (0.99-1.54) comparing the top to bottom quartile and 1.90 (1.28-2.81) for ≥10 to <1 mg/L. The corresponding OR (95% CI) for model 2 was 1.21 (0.96-1.53) and 1.86 (1.24-2.79), respectively. Results were generally similar across histotypes with the strongest associations comparing CRP levels ≥10 vs. <1mg/L, although no associations reached statistical significance. Interestingly, the impact of adjusting for BMI, smoking, and aspirin differed across subtypes. For example, the OR (95% CI) comparing the top versus bottom quartile for serous tumors increased from 1.25 (0.95-1.65) in model 1 (reproductive factors) to 1.31 (0.97-1.75) in model 2 (reproductive factors and predictors of CRP). Conversely, the association was largely attenuated for endometrioid tumors when adjusting for predictors of CRP (model 1: OR=1.37 [0.72-2.58]; model 2: OR=1.06 [0.52-2.18]). Conclusion: Our results confirm that CRP, particularly very high levels, is positively associated with risk of ovarian cancer. The association for serous tumors appeared to be independent of reproductive exposures and other factors that are associated with CRP and ovarian cancer; however, the relationship observed for endometrioid tumors was largely explained by BMI. Given that fewer risk factors have been identified for serous tumors, our work supports further exploration of inflammation and immunity in the etiology of this histotype. Further analyses will explore associations by other tumor factors (e.g., grade) and participant characteristics (e.g., menopausal status). Citation Format: Britton Trabert, Renee Fortner, Elizabeth Poole, Nicolas Wentzensen, Shelley Tworoger. C-reactive protein and ovarian cancer risk in the Ovarian Cancer Cohort Consortium. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B21.

Waist-to-Height Ratio as a Predictor of C-Reactive Protein Levels

ABSTRACTBackground: C-reactive protein is an acute-phase protein that has been found in association with adiposity and cardiovascular disease risk. In this paper, the objective was to assess the relationship of C-reactive protein to four anthropometric measurements: body mass index, waist-to-height ratio, C index, and waist circumference. Methods: A cross-sectional random sample of the Study of Cardiovascular Risk in Adolescents (Portuguese acronym “ERICA”) was included in the study. The analysis was adjusted for the complex sampling design. Poisson regression models with robust variance were used to estimate a multivariate-adjusted prevalence rate ratio expressing the relationship of each anthropometric measure to C-reactive protein. We evaluated adolescents aged 12 to 17 years participating in the capital of Porto Alegre, Brazil. Results: In all, 778 adolescents were included (60% female, 58% aged 15–17 years). Waist-to-height ratio was found to be the strongest adiposity marker associated with C-reactive protein even after adjusting for age, sex, smoking, physical activity, and insulin resistance (prevalence rate ratio = 7.09; 95% confidence interval, 5.01–9.18; p < 0.001). Conclusions: Waist-to-height ratio is a strong predictor of C-reactive protein in adolescents in Porto Alegre, Brazil.

Association between life-course socioeconomic position and inflammatory biomarkers in older age: a nationally representative cohort study in Taiwan

BackgroundEvidence of an association between low socioeconomic position (SEP) and inflammatory markers is scant. This study aimed to examine how life-course SEP predicted C-reactive protein (CRP) and interleukin (IL-6) in older age from a national cohort.MethodsWe collected data from 1036 participants in the Social Environment and Biomarkers of Aging Study in Taiwan. Four SEP time points, childhood, young adulthood, active professional life, and older age were measured retrospectively. A group-based trajectory analysis method was used to identify the distinct trajectories of life-course SEP, and trajectory group membership was used as the predictor of CRP and IL-6 levels in older age.ResultsThree trajectories of life-course SEP were identified within the total sample: Low-Low (36.5%), Low-High (26.8%), and High-High (36.7%). Participants in the High-High group had the lowest levels of CRP and IL-6. Compared with those in the Low-Low group, the participants in the Low-High group had a similar adjusted CRP [−0.032 ln mg/L; 95% confidence interval (CI) − 0.193, 0.128] and IL-6 (0.017 ln pg/mL; 95% CI −0.093, 0.128); the participants in the High-High group had a significantly lower level of adjusted CRP concentration (−0.279 ln mg/L; 95% CI: −0.434, −0.125) and similarly lower IL-6 concentration (−0.129 ln pg/mL; 95% CI −0.236, −0.023) .ConclusionsLife-course SEP is related to the level of CRP and IL-6 in older age. Our data support the notion that life-course SEP predicts inflammatory markers in older age. Low SEP in childhood is related to elevated inflammatory markers in older age. Even after the transition from low SEP in childhood to high SEP in older age, the risk remains. Further study on SEP and inflammation-related disease is warranted.

Long-term effects of birth weight and breastfeeding duration on inflammation in early adulthood.

Chronic inflammation is a potentially important physiological mechanism linking early life environments and health in adulthood. Elevated concentrations of C-reactive protein (CRP)--a key biomarker of inflammation--predict increased cardiovascular and metabolic disease risk in adulthood, but the developmental factors that shape the regulation of inflammation are not known. We investigated birth weight and breastfeeding duration in infancy as predictors of CRP in young adulthood in a large representative cohort study (n = 6951). Birth weight was significantly associated with CRP in young adulthood, with a negative association for birth weights 2.8 kg and higher. Compared with individuals not breastfed, CRP concentrations were 20.1%, 26.7%, 29.6% and 29.8% lower among individuals breastfed for less than three months, three to six months, 6-12 months and greater than 12 months, respectively. In sibling comparison models, higher birth weight was associated with lower CRP for birth weights above 2.5 kg, and breastfeeding greater than or equal to three months was significantly associated with lower CRP. Efforts to promote breastfeeding and improve birth outcomes may have clinically relevant effects on reducing chronic inflammation and lowering risk for cardiovascular and metabolic diseases in adulthood.

The lost correlation between leptin and CRP in type 2 diabetes

C reactive protein (CRP) is an inflammatory marker believed to be of value in the early prediction of type 2 diabetes (T2DM). Recent studies have shown a positive correlation between leptin and CRP levels. Here, we aimed to study the correlation between leptin and CRP in patients with T2DM. We also studied the effect of metformin therapy on the CRP-leptin correlation in patients with newly diagnosed diabetes. We performed a follow-up study on three groups of participants defined as 1: patients with newly diagnosed T2DM, 2: patients with long-standing T2DM, and 3: healthy controls. Patients with newly diagnosed diabetes were followed for three months after the initiation of metformin therapy. The homeostatic model assessment of insulin resistance (HOMA-IR) decreased, while leptin levels (15.9±1.6 versus 21.4±2.5, p<0.01) increased after metformin therapy. Leptin levels correlated significantly with CRP in healthy controls (r=0.48; p<0.01); patients with newly diagnosed diabetes before (r=0.35; p<0.05), and after (r=0.55, p<0.001) metformin therapy, while there was no significant correlation between leptin and CRP in patients with long-standing diabetes (r=0.15; p=0.55). After multiple adjustments for potential confounders, leptin was the best predictor of CRP in controls (β coefficient=0.433, p<0.01), and patients with newly diagnosed T2DM who received metformin (β coefficient=0.584, p<0.01). Statin treatment did not have any significant effect on the results. This is the first report demonstrating the restorative role of metformin on the leptin-CRP correlation in patients with newly diagnosed diabetes.

Air Pollution and Markers of Coagulation, Inflammation, and Endothelial Function

Previous studies suggest that air pollution is related to thrombosis, inflammation, and endothelial dysfunction. Mechanisms and sources of susceptibility are still unclear. One possibility is that these associations can be modified by DNA methylation states. We conducted a cohort study with repeated measurements of fibrinogen, C-reactive protein, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in 704 elderly men participating in the Veterans Administration Normative Aging Study (2000-2009). We investigated short- and intermediate-term air pollution effects on these blood markers, and epigene-environment interactions by DNA methylation of Alu, LINE-1, tissue factor (F3), Toll-like receptor 2 (TLR-2), and ICAM-1. We found effects of particle number, black carbon, nitrogen dioxide (NO(2)), and carbon monoxide (CO) on fibrinogen. Ozone was a predictor of C-reactive protein and ICAM-1. Particle number, black carbon, NO(2), CO, PM(2.5), and sulfates were associated with ICAM-1 and VCAM-1. An interquartile range increase in 24-hour exposure for NO(2) was associated with a 1.7% (95% confidence interval = 0.2%-3.3%) increase in fibrinogen for ozone; a 10.8% (2.2%-20.0%) increase in C-reactive protein for particle number; a 5.9% (3.6%-8.3%) increase in ICAM-1; and for PM(2.5), a 3.7% (1.7%-5.8%) increase in VCAM-1. The air pollution effect was stronger among subjects having higher Alu, lower LINE-1, tissue factor, or TLR-2 methylation status. We observed associations of traffic-related pollutants on fibrinogen, and both traffic and secondary particles on C-reactive protein, ICAM-1, and VCAM-1. There was effect modification by DNA methylation status, indicating that epigenetic states can convey susceptibility to air pollution.

The Association Between Self-Reported Symptoms of Recent Airway Infection and CRP Values in a General Population

C-reactive protein (CRP) is a much used biomarker for respiratory tract infection; however, the influence of airway infection on the CRP level in the general population has not been well described. The study aimed to evaluate the impact of recent symptoms of airway infection on the CRP level and how the predictive power of other known CRP predictors is influenced by taking respiratory symptoms into account. A total of 6,325 participants, aged 38–87 years, in the Tromsø Study, a repeated population-based survey, were examined with questionnaires, measurements of height and weight, spirometry, and high-sensitivity CRP analyses. The mean CRP value was 2.86 mg/L, and the geometric mean was 1.51 mg/L. Geometric means above 2.0 mg/L were found in the subgroups with the following characteristics: self-reported COPD, diabetes, recent symptoms of airway infection, forced expiratory volume in 1 s (FEV1) <80% predicted, body mass index (BMI) ≥30, and subjects treated with inhaled or oral corticosteroids. Among the subjects who reported recent airway infection, 10.5% had a CRP value of ≥10 mg/L, compared to 3.3% among the remaining participants. By multivariate analysis, BMI was the strongest independent predictor of the CRP level, followed by recent airway infection, FEV1% predicted, age, and current smoking. The study clearly demonstrates that a report of recent symptoms of airway infection strongly predicts the CRP level in the population. Such symptoms were shared rather equally between subgroups with increased CRP level, and the risk of being an important confounder in epidemiological studies is probably low. In the clinical setting, care should be taken when using the CRP level as a guide for medical prevention of chronic diseases.

Physical Activity and C-reactive Protein Levels: The Confounding Role of Body Fat

This study investigated the relationship between objectively-measured total physical activity (PA), and intensity of PA and high-sensitivity C-reactive protein (CRP) in 211 healthy, middle-age women (43.1±3.0 y). In addition, this study examined the extent to which age, BMI, abdominal circumference, and body fat percentage operated as confounders in these associations. PA was objectively measured for 7 continuous days using accelerometry. Fasting blood samples were taken, from which CRP was measured using a solid phase ELISA. Body mass index (BMI) (kg/m2), abdominal circumference measured at the umbilicus, and body fat percentage using air displacement plethysmography, were assessed. Total PA (activity counts) was significantly and inversely related to CRP concentrations (F=7.76, P=.006) as was vigorous-intensity PA. After adjusting for differences in body fat percentage, total PA and vigorous-intensity PA were no longer significant predictors of CRP. Abdominal circumference and BMI also tended to weaken the relationship between total or vigorous-intensity PA and CRP but not to the same extent as body fat percentage. These findings suggest that higher total and vigorous-intensity PA levels are significantly related to lower CRP levels in healthy, middle-age women; however, this relationship is largely a function of differences in body fat percentage.

Associations of Depressive Symptoms, Trait Hostility, and Gender With C-Reactive Protein and Interleukin-6 Response After Emotion Recall

To examine the effects of depressive symptoms and hostility on changes in C-reactive protein (CRP) and interleukin (IL)-6 in response to an acute laboratory stressor. Depressive symptoms moderate the effect of trait hostility on circulating levels of CRP and IL-6. The study included 307 men and 218 women, affording the opportunity to examine moderation by gender. Regression analyses were performed to examine depressive symptoms, hostility ratings, gender, and their interactions as predictors of CRP and IL-6 response to an emotion recall task. Analyses were adjusted for age, race, body mass index, and prerecall task levels of either CRP or IL-6. The product term for Depressive Symptoms x Hostility x Gender was not significantly related to CRP nor IL-6 response. However, Depressive Symptoms x Hostility did interact to predict CRP response (p = .002); those with the combination of high symptoms of depression and hostility had the largest CRP response. The Depressive Symptoms x Gender interaction was also a predictor of both CRP (p = .001) and IL-6 (p = .04) response; for each inflammatory marker, depressive symptoms were significantly associated with higher CRP response in women, as compared with men. Hostility did not moderate depressive symptoms, nor gender for IL-6. Our findings extend prior research by suggesting that, broadly speaking, depression is related to inflammatory markers; however, this relationship seems complex. Depression seems to be related to inflammation more strongly among hostile individuals and more strongly among women than among men.

Predictors of C-reactive protein in the national social life, health, and aging project.

Inflammation plays an important role in many chronic degenerative diseases associated with aging, and social, economic, and behavioral factors that contribute to inflammation may lead to differential burdens of morbidity and mortality in later life. This study examines socioeconomic status and race/ethnicity as predictors of C-reactive protein (CRP) among older adults in the United States and considers the degree to which health behaviors, medical conditions and medication use, and psychosocial factors account for these associations. Multiple linear regression analysis of survey data for 1,580 participants, 57-85 years of age, in a population-based nationally representative sample of community-residing older adults in the United States. Educational attainment, household wealth, and race/ethnicity were independently associated with CRP, with limited evidence for interactions with age. Health-related behaviors and usage of medications related to inflammation accounted for substantial proportions of these associations. These results highlight the fundamental causes of inflammation among older adults and suggest pathways through which social disparities in inflammation may be reduced.

Residential Traffic Exposure, Pulse Pressure, and C-reactive Protein: Consistency and Contrast among Exposure Characterization Methods

BackgroundTraffic exposure may increase cardiovascular disease (CVD) risk via systemic inflammation and elevated blood pressure, two important clinical markers for managing disease progression.ObjectivesWe assessed degree and consistency of association between traffic exposure indicators as predictors of C-reactive protein (CRP) and pulse pressure (PP) in an adult U.S. Puerto Rican population (n = 1,017).MethodsCross-sectional information on health and demographics and blood data was collected. Using multiple linear regression, we tested for associations between CRP, PP, and six traffic exposure indicators including residential proximity to roads with > 20,000 vehicles/day and traffic density [vehicle miles traveled per square mile (VMT/mi2)]. Diabetes and obesity [body mass index (BMI) ≥ 30 kg/m2] were tested as effect modifiers.ResultsCRP was positively associated with traffic density in the total population [36% CRP difference with 95% confidence interval (CI) 2.5–81%] for residence within the highest versus lowest VMT/mi2 level. With BMI ≥ 30, CRP showed significant positive associations with five of six traffic indices including residence ≤ 200 m versus > 200 m of a roadway [22.7% CRP difference (95% CI, 3.15–46.1)] and traffic density in the third highest versus lowest VMT/mi2 level [28.1% difference (95% CI, 1.0–62.6)]. PP was positively associated with residence within ≤ 100 m of a roadway for the total population [2.2 mmHg (95% CI, 0.13–4.3 mmHg)] and persons with BMI ≥ 30 [3.8 mmHg (95% CI, 0.88–6.8)]. Effect estimates approximately doubled for residence within ≤ 200 m of two or more roadways, particularly in persons with diabetes [8.1 mmHg (95% CI, 2.2–14.1)].ConclusionsTraffic exposure at roadway volumes as low as 20,000–40,000 vehicles/day may increase CVD risk through adverse effects on blood pressure and inflammation. Individuals with elevated inflammation profiles, that is, BMI ≥ 30, may be more susceptible to the effects of traffic exposure.

Determinantes do valor da proteína C-reativa em indivíduos de nível sócio-econômico muito baixo

FUNDAMENTO: Inflamação sistêmica exacerbada tem sido descrita em indivíduos de baixo nível sócio-econômico, porém estudos sobre determinantes dos valores de proteína C-reativa foram realizados apenas em países desenvolvidos. OBJETIVO: Identificar preditores de PCR em indivíduos de baixo nível SE em um país em desenvolvimento e avaliar se a PCR está relacionada ao nível SE nesse cenário. MÉTODOS: Oitenta e oito indivíduos de nível SE muito baixo foram recrutados de uma comunidade pobre, semi-rural no Brasil; 32 indivíduos de nível SE alto foram utilizados como amostra de comparação. A PCR de alta sensibilidade foi medida por nefelometria. RESULTADOS: Entre os indivíduos de baixo nível SE, os preditores independentes de PCR foram índice de massa corporal > 25 kg/m² (P<0,001), hábito de fumar (P=0,005) e condições infecciosas agudas (P=0,049). O grupo com baixo nível SE (mediana=2,02 mg/l; variação interquartil: 0,92 - 4,95 mg/dl) apresentou níveis mais altos de PCR quando comparado com o grupo de alto nível SE (1,16 mg/l, variação interquartil: 0,55 - 2,50 mg/dl, P=0,03). O índice de massa corporal foi mais alto (27 ± 4,9 kg/m² vs 25,5 ± 3,2 kg/m²; P=0,07) e a prevalência de infecção aguda foi maior (32% vs 3%, P=0,002) no grupo com baixo nível SE. Após exclusão de indivíduos com sobrepeso ou condições infecciosas, os valores de PCR foram similares entre os grupos com baixo e alto nível SE (0,93 mg/l vs 1,08 mg/l, P=0,28). CONCLUSÃO: Adiposidade, condições infecciosas e fumo são preditores de PCR em indivíduos com nível SE muito baixo. Os primeiros dois fatores são os determinantes da exacerbação da inflamação em indivíduos de muito baixo nível SE.

Severity of Mastitis Symptoms as a Predictor of C-Reactive Protein in Milk and Blood During Lactation

To investigate the presence of C-reactive protein (CRP) in breast milk and any relationship between changes in CRP in breast milk and blood, and the severity of systemic and breast symptoms experienced during mastitis. Mothers (n = 26) were followed prospectively from day 5 postpartum to the end of their lactation. Milk from each breast, blood, 24-hour urine samples and data on breast and systemic pathologies were collected at reference intervals during the first 3 months postpartum, daily during the occurrence of any breast inflammation and at 7 days after resolution of symptoms. CRP in blood was significantly increased during mastitis (p < 0.001, df:1,81; F = 31) and severity of systemic symptoms was a significant predictor for changes of CRP in blood (p < 0.01; df:3,42; F = 9.6). During mastitis both the symptomatic breast (p < 0.001; df:1,79; F = 19) and the contralateral asymptomatic breast (p < 0.004; df:1,75; F = 8.7) had a significantly higher milk CRP when compared with women with no mastitis. Although an increasing severity of breast and systemic symptoms in mastitis was predictive of an increasing CRP in milk and blood, respectively, the presence of CRP in similar concentrations in the mastitis and asymptomatic breast suggests it is of little use in making a differential diagnosis between infective verses noninfective forms of mastitis.

Fitness and Parasympathetic Tone Associated with Lower CRP in Older Adults

Exercise lowers C-reactive protein (CRP) levels, but the mechanism(s) of this effect is unknown. Exercise can reduce body fat and increase parasympathetic tone (PST), both of which may reduce CRP. The purpose of this study was to determine the potential role of fitness, fatness and HRR on hs-CRP (mg/L) levels in 85 sedentary, independently living older adults (70.4 ± 0.56 [sem] years) using baseline data from the Immune Function Intervention Trial. Exclusion criteria included: corticosteroid use, inflammatory disease, recent illness or vaccination, and smoking. Fitness was assessed using VO2 max testing, body fat using Dual-Energy X-Ray Absorptiometry (DXA), PST by the difference between maximal heart rate and 1 min heart rate recovery (HRR), and hs-CRP via ELISA. Predictors of CRP were determined using linear regression analyses. Results: Mean hs-CRP levels were 3.47 ± 0.31mg/L placing this group in a high-risk category. After adjusting for the effects of body fat, ?-blocker use, statin use, and aspirin use, fitness (beta=-.287;p=0.027) and HRR (beta=-.183; p=0.075) were independent predictors of hs-CRP. Conclusion: In this population of older adults, fitness and HRR were associated with lower levels of circulating CRP. These results suggest that exercise training may be an effective means of lowering the systemic inflammation that accompanies normal aging. The mechanism appears to be independent of fat loss. This work was supported by NIH AG-18861 to J.A. Woods.

Cystatin-C and inflammatory markers in the ambulatory elderly

Purpose Inflammatory factors are elevated in persons with severe renal dysfunction, but their association across all levels of renal function is unclear. We compared cystatin-C, a novel marker of renal function, with creatinine and estimated glomerular filtration rate (eGFR) as predictors of C-reactive protein and fibrinogen levels. Methods This study is a cross-sectional analysis to evaluate cystatin-C, creatinine, and eGFR as predictors of the inflammatory markers C-reactive protein and fibrinogen. Participants included 4637 ambulatory elderly patients from the Cardiovascular Health Study. Multivariate linear regression was used to determine the independent associations of each renal function measurement with the inflammatory marker outcomes. Results After adjustment for confounding factors, cystatin-C was correlated with both C-reactive protein (coefficient = 0.13; 95% confidence interval: 0.10-1.16, P <.0001) and fibrinogen levels (0.15; 0.13-0.18, P <.0001). Associations were larger than those for creatinine and C-reactive protein (0.05; 0.02-0.07, P = .003) or fibrinogen (0.07; 0.04-0.10, P <.0001). Adjusted levels of C-reactive protein increased incrementally across quintiles of cystatin-C, from a median of 2.2 mg/L in quintile 1 to 3.7 mg/L in quintile 5. In contrast, both C-reactive protein and fibrinogen had U-shaped associations with quintiles of creatinine and eGFR, because the inflammatory markers were equivalently elevated in quintiles 1 and 5. Conclusions The finding of a significant linear association of cystatin-C and inflammation markers suggests that even small reductions in renal function may be associated with adverse pathophysiologic consequences.

Predictors of C‐reactive protein in Tsimane' 2 to 15 year‐olds in lowland Bolivia

Infectious disease is a major global determinant of child morbidity and mortality, and energetic investment in immune defenses (even in the absence of overt disease) is an important life-history variable, with implications for human growth and development. This study uses a biomarker of immune activation (C-reactive protein) to investigate an important aspect of child health among the Tsimane', a relatively isolated Amerindian population in lowland Bolivia. Our objectives are twofold: 1) to describe the distribution of CRP by age and gender in a cross-sectional sample of 536 2-15-year-olds; and 2) to explore multiple measures of pathogen exposure, economic resources, and acculturation as predictors of increased CRP. The median blood-spot CRP concentration was 0.73 mg/l, with 12.9% of the sample having concentrations greater than 5 mg/L, indicating a relatively high degree of immune activation in this population. Age was the strongest predictor of CRP, with the highest concentrations found among younger individuals. Increased CRP was also associated with higher pathogen exposure, lower household economic resources, and increased maternal education and literacy. The measurement of CRP offers a direct, objective indicator of immune activation, and provides insights into a potentially important pathway through which environmental quality may shape child growth and health.

Lack of concordance between plasma markers of cardiovascular risk and intima-media thickness in patients with type 2 diabetes.

Endothelial dysfunction, oxidative stress and systemic inflammation play an important role in the enhanced cardiovascular risk in diabetes. Carotid intima-media thickness (IMT), a widely accepted marker of subclinical atherosclerosis, is known to be increased in patients with type 2 diabetes. The relationships between plasma markers of cardiac risk and carotid IMT are not well known. We therefore studied a group of patients with type 2 diabetes to evaluate the relationships between plasma markers of cardiac risk and carotid IMT. We measured carotid IMT and the levels of soluble endothelial adhesion molecules [sE-selectin, intercellular cell adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1)], C-reactive protein (CRP) and 8-isoprostane in 40 patients with type 2 diabetes without clinical macrovascular complications (HbA1c<10%, duration of diabetes<12 years) and 25 healthy subjects. We then examined the correlations between these plasma markers, carotid IMT and various clinical and biochemical parameters. Diabetic patients had higher plasma sE-selectin (p=0.03), sICAM-1 (p=0.05), CRP (p=0.047) and 8-isoprostane (p=0.001) concentrations than control subjects. Mean IMT values were identical (0.63 +/- 0.02 mm) in diabetic (range, 0.40-0.92 mm) and healthy subjects (range, 0.45-0.85 mm). In diabetic patients, stepwise multivariate analysis showed that HbA1c and plasma glucose were independent predictors of sE-selectin (r2=0.19 and r2=0.17, p<0.01, respectively), whereas waist circumference and body mass index (BMI) were predictors of sICAM-1 (r2=0.27, p=0.001 and r2=0.22, p=0.002, respectively). Waist circumference was the only predictor of CRP (r2=0.2, p<0.01), and systolic blood pressure was the only predictor of 8-isoprostane (r2=0.19, p=0.006). In control subjects, similar analysis showed that plasma glucose and waist circumference were predictors of sE-selectin and sICAM-1, respectively (r2=0.2, p<0.05). These results indicate that some well-controlled type 2 diabetic patients free of clinical macrovascular complications have elevated plasma markers of cardiovascular risk without having increased IMT. The elevation of plasma markers of endothelial cell activation (sE-selectin and s-ICAM-1) or inflammation (CRP) and oxidative stress (8-isoprostane) in diabetics vs. controls is distinct from and cannot be explained simply by differences in the burden of atherosclerosis as assessed by carotid IMT.

The relationship between simple anthropometric indices and c-reactive protein: ethnic and gender differences

C-reactive protein (CRP) is an independent risk factor for cardiovascular disease (CVD) that is strongly associated with indicators of body fat, yet the effect of potential confounders, such as ethnic background and gender has not been characterized. Our purpose was to determine the effect ethnicity and gender has on the relationship between CRP, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) in men and women of Chinese and European descent. BMI, WC, WHR, and CRP were measured in European (n = 91) and Chinese (n = 91) men and women recruited from local hospital staff. Pearson correlation coefficients were determined between CRP, age, and anthropometric measures for the entire cohort and stratified by ethnicity and gender. Multiple regression analyses were performed using interactions between BMI, WC, and WHR for each ethnicity and gender with CRP as the outcome. CRP levels were significantly lower in Chinese compared with Europeans, but this difference disappeared after correction for either BMI or WC. In women, BMI ( r = .55, P < .01) and WC ( r = .59, P < .01) correlated with CRP. Gender significantly interacted with WC to predict CRP after adjusting for age, smoking status, alcohol, and BMI ( P < .05). There was a nonsignificant interaction between gender and BMI as a predictor of CRP. Differences in CRP remained significant after adjusting for WHR. The relationship between CRP levels and BMI or WC was similar between men and women of Chinese and European descent. Gender significantly modified the relationship between CRP and WC. At a WC beyond 70 cm, CRP levels increased at a greater rate in women than men.

Relationship of total and abdominal adiposity with CRP and IL-6 in women.

To examine the relationship between different measures of adiposity as predictors of C-reactive protein (CRP) and interleukin-6 (IL-6) levels. A cross-sectional study of 733 women free from preexisting cardiovascular disease or cancer at baseline. Total adiposity, as measured by body mass index (BMI). Abdominal adiposity, as measured by waist circumference (WC) and waist/hip ratio (WHR). High sensitivity CRP levels and IL-6 levels. BMI, WHR, and WC were all significantly correlated with CRP and IL-6, throughout the anthropometric spectrum. After adjustment for risk factors, the odds ratios (ORs) were 12.2 (95% CI, 6.44-23.0) for elevated CRP (>/=75th percentile) and 4.13 (95% CI, 2.37-7.18) for elevated IL-6 (>/=75th percentile) in comparisons of extreme BMI quartiles. Among women in the highest WC quartile, the OR for elevated CRP and IL-6 were 8.57 (95% CI, 4.59-16.0) and 4.40 (95%CI, 2.46-7.89), while ORs for the highest WHR quartile were 2.88 (95% CI, 1.60-5.19) and 1.76 (95% CI, 1.03-3.01), respectively. Compared with lean nonusers, women in the highest BMI quartile who did not use hormone therapy (HT) had an OR for elevated CRP of 7.79 (95% CI, 2.08-29.2) vs. 31.6 (95% CI, 7.97-125.6) for current hormone users. Indices of both total and abdominal adiposity were strongly associated with significant increased levels of CRP and IL-6. This association was evident across the entire spectrum of BMI.