Log C-reactive Protein Research Articles

P5505Inflammation implicated in the aetiology of major vascular and non-vascular diseases in East Asians

Abstract Background Mendelian randomisation (MR) studies using genetic variants in the IL6R gene encoding the interleukin-6 (IL-6) receptor have demonstrated that IL-6 plays a causal role in the aetiology of coronary heart disease (CHD) in European populations, with implications for the development of drugs targeting inflammation-related pathways. It is less clear whether IL-6 signalling plays a causal role in vascular disease or major non-vascular diseases in East Asians. Purpose Using an MR approach, we investigated associations of altered IL-6 signalling with subtypes of CHD, stroke, cancer and respiratory disease in a large East Asian cohort. Methods In approximately 150,000 Chinese adults from the China Kadoorie Biobank, we investigated associations of rs7529229 (in strong linkage disequilibrium, r2=0.99, with the IL6R Asp358Ala variant rs2228145) with blood biomarkers and selected disease events in which inflammation has previously been implicated. First, we used linear regression to quantify the per-allele association of rs7529229 with levels in plasma of log-transformed C-reactive protein (CRP) (n=17,866), fibrinogen (n=9,255), and IL-6 protein (n=633). Second, we used logistic regression to evaluate the association of rs7529229 with incidence of CHD, stroke, cancer, and respiratory disease events. All models were adjusted for age, age-squared, sex (except breast cancer), and case ascertainment (for CRP and fibrinogen), and stratified by recruitment region. We assessed significance at a 5% false discovery rate. Results IL6R rs7529229 C-allele was associated with lower log CRP (–0.11 SDs per C-allele; p=4.9x10–25) and log fibrinogen (–0.07 SDs; p=2.2x10–7), and higher log IL-6 (0.15 SDs; p=0.011) (Figure 1), mimicking therapeutic blockade of IL6R. IL6R rs7529229 was associated with a lower risk of acute myocardial infarction (n=4,047 cases; OR: 0.92 [95% CI 0.88–0.96] per C-allele; p=2.8x10–4), with the association similar for fatal and non-fatal cases (Figure 2). There was no evidence of association with ischaemic stroke (n=18,315; OR: 1.00 [0.98–1.03]; p=0.90) or intracerebral haemorrhage (n=7,372; OR: 1.03 [0.99–1.07]; p=0.10). For non-cardiovascular diseases, the IL6R rs7529229 was associated with a lower risk of oesophageal (n=824; OR: 0.88 [0.79–0.97] per C-allele; p=0.013) and colorectal (n=1,151; OR: 0.89 [0.82–0.97]; p=8.3x10–3) cancers, but a higher risk of tuberculosis (n=1,017; OR: 1.15 [1.05–1.26]; p=2.4x10–3). Conclusion The results of the present study are consistent with a causal role for the IL-6 signalling pathway in the aetiology of myocardial infarction and some cancers, but not of stroke. These findings provide further genetic support for drug development targeting inflammation in the prevention and treatment of coronary and selected cancer outcomes. Acknowledgement/Funding Kadoorie Charitable Foundation, UK Wellcome Trust, Chinese Ministry of Science and Technology, BHF, CRUK, NIHR

Neural network and logistic regression diagnostic prediction models for giant cell arteritis: development and validation.

PurposeTo develop and validate neural network (NN) vs logistic regression (LR) diagnostic prediction models in patients with suspected giant cell arteritis (GCA). Design: Multicenter retrospective chart review.MethodsAn audit of consecutive patients undergoing temporal artery biopsy (TABx) for suspected GCA was conducted at 14 international medical centers. The outcome variable was biopsy-proven GCA. The predictor variables were age, gender, headache, clinical temporal artery abnormality, jaw claudication, vision loss, diplopia, erythrocyte sedimentation rate, C-reactive protein, and platelet level. The data were divided into three groups to train, validate, and test the models. The NN model with the lowest false-negative rate was chosen. Internal and external validations were performed.ResultsOf 1,833 patients who underwent TABx, there was complete information on 1,201 patients, 300 (25%) of whom had a positive TABx. On multivariable LR age, platelets, jaw claudication, vision loss, log C-reactive protein, log erythrocyte sedimentation rate, headache, and clinical temporal artery abnormality were statistically significant predictors of a positive TABx (P≤0.05). The area under the receiver operating characteristic curve/Hosmer–Lemeshow P for LR was 0.867 (95% CI, 0.794, 0.917)/0.119 vs NN 0.860 (95% CI, 0.786, 0.911)/0.805, with no statistically significant difference of the area under the curves (P=0.316). The misclassification rate/false-negative rate of LR was 20.6%/47.5% vs 18.1%/30.5% for NN. Missing data analysis did not change the results.ConclusionStatistical models can aid in the triage of patients with suspected GCA. Misclassification remains a concern, but cutoff values for 95% and 99% sensitivities are provided (https://goo.gl/THCnuU).

Geriatric nutritional risk index predicts all-cause deaths in heart failure with preserved ejection fraction.

AimsThe objective of the study was to evaluate whether the geriatric nutritional risk index (GNRI) at discharge may be helpful in predicting the long‐term prognosis of patients hospitalized with heart failure (HF) with preserved ejection fraction (HFpEF, left ventricular ejection fraction ≥50%), a common HF phenotype in the elderly.Methods and resultsOverall, 110 elderly HFpEF patients (≥65 years) from the Ibaraki Cardiovascular Assessment Study‐HF (n = 838) were enrolled. The mean age was 78.5 ± 7.2 years, and male patients accounted for 53.6% (n = 59). All‐cause mortality was compared between the low GNRI (<92) with moderate or severe nutritional risk group and the high GNRI (≥92) with no or low nutritional risk group. Cox proportional hazard regression models were constructed to evaluate the influence of the GNRI on all‐cause death with the following covariates using forward stepwise selection: age, sex, nutritional status based on the GNRI as a categorical variable, history of HF hospitalization, haemoglobin level, estimated glomerular filtration rate, log brain natriuretic peptide levels (logBNP), history of hypertension, log C‐reactive protein levels, left ventricular ejection fraction, left ventricular mass index, and the New York Heart Association functional classification (I/II or III class). The prognostic value of the GNRI was compared with that of serum albumin using C‐statistics. The GNRI was added to the logBNP, serum albumin or the body mass index was added to the logBNP, and the C‐statistic was compared using DeLong's test. Cox regression analysis revealed that age and a low GNRI were independent predictors of all‐cause death (P < 0.05, n = 103; hazard ratio = 1.095, 95% confidence interval = 1.031–1.163, for age, and hazard ratio = 3.075, 95% confidence interval = 1.244–7.600, for the GNRI). DeLong's test for the two correlated receiver operating characteristic curves [area under the receiver operating characteristic curve (AUROC) of serum albumin, 0.71; AUROC of the GNRI, 0.75] demonstrated significant differences between the groups (P = 0.038). Adding the GNRI to the logBNP increased the AUROC for all‐cause death significantly (0.71 and 0.80, respectively; P = 0.040, n = 105). The addition of serum albumin or the body mass index to the logBNP did not significantly increase the AUROC for all‐cause death (P = 0.082 and P = 0.29, respectively).ConclusionsNutritional screening using the GNRI at discharge is helpful to predict the long‐term prognosis of elderly HFpEF patients.

Low serum albumin as a risk factor for infection-related in-hospital death among hemodialysis patients hospitalized on suspicion of infectious disease: a Japanese multicenter retrospective cohort study

BackgroundSerum albumin is a marker of nourishment and inflammation. Although hypoalbuminemia in hemodialysis patients is reported as a risk factor for poor prognosis, few studies describe its effects on infectious diseases specifically. This study aimed to examine the relationship between the serum albumin level on admission and infection-related in-hospital death among hemodialysis patients.MethodsThis was a multicenter retrospective observational study that was undertaken in Japan. We reviewed the medical records of 507 hemodialysis patients aged > 18 years, whose blood cultures were obtained based on suspicion of infectious disease, and who were managed at seven Japanese tertiary dialysis units from August 2011 to July 2013. The outcome measure was infection-related in-hospital death. Multivariate logistic regression models adjusted for age, sex, the dialysis vintage, diabetes mellitus, bacteremia, and log C-reactive protein levels were used for the statistical analysis.ResultsFour hundred patients were analyzed and allocated to three groups based on their serum albumin levels: marked hypoalbuminemia (< 2.5 mg/dL), mild hypoalbuminemia (≤ 2.5–< 3.5 mg/dL), and normal albumin levels (≤ 3.5 mg/dL). The infection-related in-hospital death rates were 22.9% (n = 11), 12.5% (n = 25), and 4.6% (n = 7), respectively. The multivariate logistic regression models determined that a low serum albumin level was an independent risk factor for infection-related in-hospital death (odds ratio 0.35, 95% confidence interval 0.18–0.66).ConclusionsA low serum albumin level strongly predicts infection-related in-hospital death in hemodialysis patients hospitalized on suspicion of infection. Like those with bacteremia or diabetes mellitus, hemodialysis patients with hypoalbuminemia require careful management of their infections.

Use of Proteomic and Hematology Biomarkers for Prediction of Hematopoietic Acute Radiation Syndrome Severity in Baboon Radiation Models.

Use of plasma proteomic and hematological biomarkers represents a promising approach to provide useful diagnostic information for assessment of the severity of hematopoietic acute radiation syndrome. Eighteen baboons were evaluated in a radiation model that underwent total-body and partial-body irradiations at doses of Co gamma rays from 2.5 to 15 Gy at dose rates of 6.25 cGy min and 32 cGy min. Hematopoietic acute radiation syndrome severity levels determined by an analysis of blood count changes measured up to 60 d after irradiation were used to gauge overall hematopoietic acute radiation syndrome severity classifications. A panel of protein biomarkers was measured on plasma samples collected at 0 to 28 d after exposure using electrochemiluminescence-detection technology. The database was split into two distinct groups (i.e., "calibration," n = 11; "validation," n = 7). The calibration database was used in an initial stepwise regression multivariate model-fitting approach followed by down selection of biomarkers for identification of subpanels of hematopoietic acute radiation syndrome-responsive biomarkers for three time windows (i.e., 0-2 d, 2-7 d, 7-28 d). Model 1 (0-2 d) includes log C-reactive protein (p < 0.0001), log interleukin-13 (p < 0.0054), and procalcitonin (p < 0.0316) biomarkers; model 2 (2-7 d) includes log CD27 (p < 0.0001), log FMS-related tyrosine kinase 3 ligand (p < 0.0001), log serum amyloid A (p < 0.0007), and log interleukin-6 (p < 0.0002); and model 3 (7-28 d) includes log CD27 (p < 0.0012), log serum amyloid A (p < 0.0002), log erythropoietin (p < 0.0001), and log CD177 (p < 0.0001). The predicted risk of radiation injury categorization values, representing the hematopoietic acute radiation syndrome severity outcome for the three models, produced least squares multiple regression fit confidences of R = 0.73, 0.82, and 0.75, respectively. The resultant algorithms support the proof of concept that plasma proteomic biomarkers can supplement clinical signs and symptoms to assess hematopoietic acute radiation syndrome risk severity.

C-reactive protein as a predictor of posttraumatic stress induced by acute myocardial infarction.

Acute coronary syndrome (ACS) may cause clinically relevant posttraumatic stress disorder symptoms (PTSS). An inflammatory state might be one mechanism linking PTSS with poor prognosis after ACS. We tested the hypothesis that a change in C-reactive protein (CRP) between hospital admission and 3-month follow-up is an independent predictor of ACS-triggered PTSS. We assessed 183 patients (median age 59 years; 84% men) with verified myocardial infarction (MI) within 48 h of an acute coronary intervention and three months post-MI for self-rated PTSS. 14 (7.7%) patients fulfilled definition criteria for PTSS caseness. CRP values were categorized according to the predicted risk of cardiovascular disease (CVD) at hospital admission (acute inflammatory response): 0 to <5 mg/L, 5 to <10 mg/L, 10 to <20 mg/L, and ≥ 20 mg/L; and at 3-month follow-up (low-grade inflammation): 0 to <1 mg/L, 1 to <3 mg/L, and ≥ 3 mg/L. Additionally, in a subsample of 84 patients with CRP levels below 20 mg/L at admission, CRP values were log-transformed. After adjustment for covariates, less of a reduction or an increase of log CRP values between admission and 3-month follow-up predicted PTSS caseness (OR 6.25, 95% CI 1.25, 31.38), and continuous PTSS (unstandardized B = 0.21, 95% CI 0.07, 4.19; p = 0.043). Less reduction in CRP risk categories predicted both PTSS caseness (OR 4.14, 95% CI 1.89, 9.06) and continuous PTSS (B = 1.80, 95% CI 1.09, 2.51; p < 0.001). Persistently heightened inflammation seems to be predictive for the development of PTSS three months after ACS, so interventions to lower inflammation might be warranted.

Central Blood Pressure Parameters Correlate with Cardiac Structure and Function in Healthy Chinese Individuals without Cardiovascular Disease

Purpose: To explore the relationship between central blood pressure (BP) parameters and cardiac structure and function parameters in healthy individuals. Methods: Four hundred Chinese participants with no overt cardiovascular disease participated in this study. One hundred and seventy-one participants (42.8%) were male and the mean age was 60 years. Central BP was measured with the SphygmoCor system. Cardiac structure and function were assessed by echocardiography. Results: We showed a significant association of left atrial volume and left ventricular mass index (LVMI) with brachial and central systolic BP (SBP) and pulse pressure (PP; r = 0.189–0.0.39, p < 0.001). Left ventricular diastolic function and the E/A ratio were significantly associated with brachial and central BP (r = 0.228–0.469, p < 0.001). Multivariate regression analysis revealed that central SBP and PP were independently correlated with LVMI after normalization for age and other confounding variables (sex, body mass index, smoking, and alcohol intake, and the levels of triglycerides, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid, fasting blood glucose, log C-reactive protein, and fibrinogen. However, only central SBP was found to be independently correlated with the E/A ratio. Conclusions: Cardiac structure and diastolic function were associated with brachial and central BP. However, after normalization, cardiac structure parameters were independently correlated with central SBP and PP. Diastolic function was the only cardiac function parameter that correlated with central SBP.

Increased prevalence of peripheral arterial disease in patients with obese sarcopenia undergoing hemodialysis.

Background peripheral arterial disease (PAD) is a common complication in patients undergoing dialysis, which reduces the quality of life and increases the risk of mortality. Recent literature has documented an association between increased visceral fat (VF) content and a proatherogenic factors in end-stage renal disease. The present study investigated the prevalence of PAD in patients undergoing hemodialysis. PAD was determined as an ankle-brachial index <0.9. Additionally, VF content was determined using multiple frequency bioelectrical impendence analysis. The nutritional status of the patients was evaluated by subjective global assessment and endothelial function was measured by ultrasonographic brachial artery flow-mediated dilatation. Patients divided into two groups (malnourished and non-malnourished) with two further subgroups in each (high VF and low VF content). The prevalence of PAD was identified to be significantly higher in patients with a high VF mass compared with a low VF mass in non-malnourished patients. PAD was significantly more common in malnourished patients compared with non-malnourished patients (P<0.01). The presence of PAD in patients undergoing hemodialysis was identified to be significantly correlated with age, diabetes mellitus (DM) status VF content, malnutrition, serum albumin level, diastolic blood pressure and log C-reactive protein levels. Furthermore, logistic regression analysis determined that age, DM, VF content and malnutrition were significant independent risk factors for PAD in patients undergoing hemodialysis. In conclusion, the results of the present study indicated that obesity and malnutrition act synergistically to increase the risk of PAD in patients undergoing dialysis.

Lower ocular pulse amplitude with dynamic contour tonometry is associated with biopsy-proven giant cell arteritis

ObjectivesTo determine the role of the ocular pulse amplitude (OPA) from Pascal dynamic contour tonometry in predicting the temporal artery biopsy (TABx) result in patients with suspected giant cell arteritis (GCA). DesignProspective validation study. ParticipantsAdults aged 50 years or older who underwent TABx from March 2015 to April 2017. MethodsSubjects on high-dose glucocorticoids more than 14 days or without serology before glucocorticoid initiation were excluded. The OPA from both eyes was obtained and averaged just before TABx of the predominantly symptomatic side. The variables chosen for the a priori prediction model were age, average OPA, and C-reactive protein (CRP). Erythrocyte sedimentation rate (ESR), platelets, jaw claudication, and eye findings were also recorded. In this study, subjects with a negative biopsy were considered not to have GCA, and contralateral biopsy was performed if the clinical suspicion for GCA remained high. An external validation set (XVAL) was obtained. ResultsOf 109 TABx, 19 were positive and 90 were negative. On univariate logistic regression, the average OPA had 0.60 odds for positive TABx (p = 0.03), with no statistically significant difference in age, sex, CRP, ESR, or jaw claudication. In suspected GCA, an OPA of 1 mm Hg had positive likelihood ratio 4.74 and negative likelihood ratio 0.87 for positive TABx. Multivariate regression of the prediction model using optimal mathematical transforms (inverse OPA, log CRP, age >65 years) had area under the receiver operating characteristic curve (AUROC) = 0.85 and AUROCXVAL = 0.81. ConclusionsOPA is lower in subjects with biopsy-proven GCA and is a statistically significant predictor of GCA.

Is serum bilirubin associated with the severity of Guillain–Barré syndrome?

ABSTRACTObjective: Our aim was to assess the correlation between serum bilirubin levels and Guillain–Barré syndrome (GBS).Patients and methods: One hundred and one newly diagnosed patients with Guillain–Barré syndrome and 111 healthy age- and sex-matched individuals in the First Affiliated Hospital of Guangxi Medical University (Guangxi, China) from June 2012 to May 2017 were included in this study. Clinical characteristics and laboratory parameters of Guillain–Barré syndrome patients and healthy controls were retrospectively analysed.Results: Serum bilirubin levels in Guillain–Barré syndrome patients were significantly lower as compared with those in healthy controls (p < 0.001); besides, log C-reactive protein and erythrocyte sedimentation rate were significantly higher. We found that there was a negative correlation between GBS disability scale scores and total bilirubin, direct bilirubin, indirect bilirubin (r = −0.541, P < 0.001; r = −0.403, P < 0.001; r = −0.526, P < 0.001), respectively. Among patients with GBS, serum total bilirubin, direct bilirubin, and indirect bilirubin levels were independently associated with Guillain–Barré syndrome disability scale scores in multiple linear regression analysis, respectively.Conclusions: We observed that serum bilirubin levels were lower in patients with Guillain–Barré syndrome, and suggested total bilirubin, direct bilirubin, and indirect bilirubin were independently and inversely associated with Guillain–Barré syndrome severity.

Immediate and late outcomes of endovascular therapy for lower extremity arteries in Buerger disease

ObjectiveBuerger disease is a rare inflammatory vasculopathy presenting with severe claudication or critical limb ischemia. In this study, we sought to evaluate the feasibility and clinical outcomes of endovascular therapy for Buerger disease involving arteries in the lower extremities. MethodsBetween January 2006 and May 2016, there were 44 Buerger disease patients (43 men; mean age, 40.4 ± 9.6 years) with 50 target limbs treated by endovascular therapy at the Severance Cardiovascular Hospital. Baseline characteristics as well as both immediate and late clinical outcomes were retrospectively analyzed. ResultsThe majority (86.4%) of patients presented with critical limb ischemia. A total of 88 target lesions in 50 limbs were treated with endovascular procedures. All limbs showed infrapopliteal artery occlusions, and multilevel diseases involving the iliac or femoropopliteal artery were found in 31 patients (62%). Technical success was achieved in 80% of subjects. We found that a lower serum level of C-reactive protein, specifically the log C-reactive protein value (odds ratio, 0.03; 95% confidence interval [CI], 0.00-0.71; P = .030), was an independent predictor of technical failure. The median follow-up duration was 29 months. Major adverse limb event-free survival and reintervention- and amputation-free survival were 83.3% and 67.9% at 3 years, respectively. In a multivariate Cox proportional hazards analysis, previous endovascular treatment (hazard ratio, 3.70; 95% CI, 1.20-11.31; P = .022) and previous amputation (hazard ratio, 4.68; 95% CI, 1.37-15.96; P = .014) were identified as independent risk factors for reintervention- and amputation-free survival. ConclusionsIn patients with Buerger disease, endovascular treatment achieved technical success in the majority of the cases and was associated with favorable immediate and late clinical outcomes. These findings indicate that endovascular therapy may be considered a first-line treatment option for severe symptomatic patients with Buerger disease.

Multivariable prediction model for suspected giant cell arteritis: development and validation.

PurposeTo develop and validate a diagnostic prediction model for patients with suspected giant cell arteritis (GCA).MethodsA retrospective review of records of consecutive adult patients undergoing temporal artery biopsy (TABx) for suspected GCA was conducted at seven university centers. The pathologic diagnosis was considered the final diagnosis. The predictor variables were age, gender, new onset headache, clinical temporal artery abnormality, jaw claudication, ischemic vision loss (VL), diplopia, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet level. Multiple imputation was performed for missing data. Logistic regression was used to compare our models with the non-histologic American College of Rheumatology (ACR) GCA classification criteria. Internal validation was performed with 10-fold cross validation and bootstrap techniques. External validation was performed by geographic site.ResultsThere were 530 complete TABx records: 397 were negative and 133 positive for GCA. Age, jaw claudication, VL, platelets, and log CRP were statistically significant predictors of positive TABx, whereas ESR, gender, headache, and temporal artery abnormality were not. The parsimonious model had a cross-validated bootstrap area under the receiver operating characteristic curve (AUROC) of 0.810 (95% CI =0.766–0.854), geographic external validation AUROC’s in the range of 0.75–0.85, calibration pH–L of 0.812, sensitivity of 43.6%, and specificity of 95.2%, which outperformed the ACR criteria.ConclusionOur prediction rule with calculator and nomogram aids in the triage of patients with suspected GCA and may decrease the need for TABx in select low-score at-risk subjects. However, misclassification remains a concern.

Body Composition and Inflammation in Hemodialysis Patients.

The volume state of dialysis patients is important in guiding the dialysis process. Volume overload in these patients is associated with inflammation. The objectives of the present study were to assess the body composition of patients on hemodialysis; to determine the concentrations of B-type natriuretic peptide (BNP) in plasma and evaluate the association of BNP concentrations with volume overload; to determine the concentrations of C-reactive protein (CRP), albumin and superoxide dismutase (SOD) activities as indicators of inflammatory or antioxidant processes. The study included 79 maintenance hemodialysis patients. Assessment of body compartments was carried out using a body composition monitor (BCM). After BCM measurements, blood samples were taken from the patients for laboratory tests. There were 40 (50.6%) volume-overloaded patients (relative overhydration >15%). These patients had a higher prevalence of arterial hypertension (P < 0.05), significantly higher concentrations of BNP (P = 0.01), lower body mass index (P < 0.05) and lower fat tissue index (P < 0.05). There was a positive correlation between plasma BNP and CRP concentrations (ρ = 0.231; P < 0.05), and a negative correlation between (log) BNP and albumin (r = -0.021; P < 0.05), as well as (log) CRP and albumin concentrations (r = -3; P < 0.01). SOD activity was positively correlated with albumin concentrations (r = 0.254; P < 0.05). The concentrations of BNP in this study were associated with volume overload and inflammatory markers. Patients with a higher albumin concentration had higher SOD activity.

Sedentary Behaviors and Biomarkers Among Breast Cancer Survivors.

Sedentary behavior is associated with increased risk of poor outcomes in breast cancer survivors, but underlying mechanisms are not well understood. This pilot study explored associations between different aspects of sedentary behaviors (sitting, prolonged sitting, sit-to-stand transitions, and standing) and breast cancer risk-related biomarkers in breast cancer survivors (n = 30). Sedentary behavior variables were objectively measured with thigh-worn activPALs. Breast cancer risk-related biomarkers assessed were C-reactive protein (CRP), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) and were measured in fasting plasma samples. Linear regression models were used to investigate associations between sedentary behavior variables and biomarkers (log CRP, insulin, and HOMA-IR). Sit-to-stand transitions were significantly associated with insulin resistance biomarkers (P < .05). Specifically, each 10 additional sit-to-stand transitions per day was associated with a lower fasting insulin concentration (β = -5.52; 95% CI, -9.79 to -1.24) and a lower HOMA-IR value (β = -0.22; 95% CI, -0.42 to -0.03). Sit-to-stand transitions were not significantly associated with CRP concentration (P = .08). Total sitting time, long sitting bouts, and standing time were not significantly associated with CRP, insulin, or HOMA-IR (P > .05). Sit-to-stand transitions may be an intervention target for reducing insulin resistance in breast cancer survivors, which may have favorable downstream effects on cancer prognosis.

Genetic and environmental influences on stability and change in baseline levels of C-reactive protein: A longitudinal twin study

Background and aimsCross-sectional twin and family studies report a moderate heritability of baseline levels of C-reactive protein (CRP), ranging from 0.10 to 0.65 for different age ranges. Here, we investigated the stability and relative impact of genetic and environmental factors underlying serum levels of CRP, using a longitudinal classical twin design. MethodsA maximum of 6201 female twins from the TwinsUK registry with up to three CRP measurements (i.e. visit 1 [V1], visit 2 [V2] and visit 3 [V3]) over a 10-year follow-up period were included in this study. Structural equation modeling was applied to dissect the observed phenotypic variance into its genetic and environmental components. To estimate the heritability of CRP as well as its genetic and environmental correlations across different time points, a trivariate model was used. ResultsNatural log (ln) CRP levels significantly increased from V1 to V2 (p=4.4 × 10−25) and between V1 and V3 (p=1.2 × 10−15), but not between V2 and V3. The median (IQR) follow-up time between V1 and V3 was 9.58 (8.00–10.46) years. Heritability estimates for CRP were around 50% and constant over time (0.46–0.52). Additionally, adjustment for BMI did not meaningfully change the heritability estimates (0.49–0.51). The genetic correlations between visits were significantly smaller than one, ranging from 0.66 to 0.85. ConclusionsThe present study provides evidence for stable heritability estimates of CRP of around 50% with advancing age. However, between-visit genetic correlations are significantly lower than 1, indicating emergence of new genetic effects on CRP levels with age.

Re-employment, job quality, health and allostatic load biomarkers: prospective evidence from the UK Household Longitudinal Study.

BackgroundThere is little evidence on whether becoming re-employed in poor quality work is better for health and well-being than remaining unemployed. We examined associations of job transition with health and chronic stress-related biomarkers among a population-representative cohort of unemployed British adults.MethodsA prospective cohort of 1116 eligible participants aged 35 to 75 years, who were unemployed at wave 1 (2009/10) of the UK Household Longitudinal Study, were followed up at waves 2 (2010/11) and 3 (2011/12) for allostatic load biomarkers and self-reported health. Negative binomial and multiple regression models estimated the association between job adversity and these outcomes.ResultsCompared with adults who remained unemployed, formerly unemployed adults who transitioned into poor quality jobs had higher levels of overall allostatic load (0.51, 0.32–0.71), log HbA1c (0.06, <0.001–0.12), log triglycerides (0.39, 0.22–0.56), log C-reactive protein (0.45, 0.16–0.75), log fibrinogen (0.09, 0.01–0.17) and total cholesterol to high-density lipoprotein (HDL) ratio (1.38, 0.88–1.88). Moreover, physically healthier respondents at wave 1 were more likely to transition into good quality and poor quality jobs after 1 year than those who remained unemployed.ConclusionsFormerly unemployed adults who transitioned into poor quality work had greater adverse levels of biomarkers compared with their peers who remained unemployed. The selection of healthier unemployed adults into these poor quality or stressful jobs was unlikely to explain their elevated levels of chronic stress-related biomarkers. Job quality cannot be disregarded from the employment success of the unemployed, and may have important implications for their health and well-being.

The Contribution of Inflammation to the Development of Hypertension Mediated by Increased Arterial Stiffness.

BackgroundThe mechanisms underlying the possible contribution of chronic inflammation to the development of hypertension remain unclear. We examined the longitudinal association of inflammation with the progression of vascular and/or renal abnormalities in the development of hypertension.Methods and ResultsIn 3274 middle‐aged Japanese men without hypertension at the study baseline, brachial‐ankle pulse wave velocity, blood pressure, estimated glomerular filtration rate, and serum CRP (C reactive protein) levels were measured annually during a 9‐year period. During this study period, 474 participants (14.5%) developed hypertension. Analysis of the repeated‐measures data revealed that sustained elevation of serum CRP levels was associated with a longitudinal increase of the brachial‐ankle pulse wave velocity. A linear mixed model analysis revealed that higher log‐transformed serum CRP values (log CRP) at each measurement were associated with a higher annual increase of the brachial‐ankle pulse wave velocity (estimate=32.553±11.635 cm/s per log CRP, P=0.018), and that higher values of the brachial‐ankle pulse wave velocity at each measurement were associated with a higher annual elevation of blood pressure (estimate=0.025±0.002 mm Hg per log CRP, P<0.001).ConclusionsIn middle‐aged Japanese men without hypertension at study baseline, long‐term active inflammation appears to be associated with a longitudinal increase of arterial stiffness. In turn, this longitudinal increase of arterial stiffness appears to be associated with longitudinal elevation of blood pressure to the hypertensive range. Thus, systemic inflammation may play a role in the pathogenesis of hypertension by the progression of arterial stiffness.

The role of laser Doppler flowmetry tests, serum angiopoietin-2, asymmetric and symmetric dimethylarginine to predict outcome in chronic kidney disease.

The role of biochemical and functional markers of microvascular dysfunction to predict cardiovascular outcomes in nondialyzed chronic kidney disease (CKD) remains unclear. In this prospective cohort study, we assessed whether biochemical [serum level of angiopoietin-2 (Ang-2), asymmetric and symmetric dimethylarginin] and functional (laser Doppler flowmetry) measures of microvascular function predicted cardiovascular events, cardiovascular and all-cause mortality in CKD patients. Postocclusive reactive hyperemia area (PORHHA), acetylcholine and sodium nitroprusside-mediated flow changes were estimated by laser Doppler flowmetry, and Ang-2, asymmetric and symmetric dimethylarginin were assessed in 105 CKD patients at baseline. Multiple failure time Cox-regression analyses with backward elimination were performed to determine the predictors of the combined endpoint of cardiovascular mortality and cardiovascular events or all-cause mortality and cardiovascular events during a median of 66.6 (interquartile range 39.8-80.4) months of follow-up. In univariate models lnAng-2 and lnPORHHA both predicted the cardiovascular outcome besides age, diabetes, baseline cardiovascular disease, brachial pulse pressure and log C-reactive protein. In multivariate analysis lnPORHHA [hazard ratio: 0.66 (95% confidence interval: 0.49-0.89) per ln(mU s)], age [1.03 (1.01-1.06) per year], log C-reactive protein [1.31 (1.06-1.64) per ln(mg/l)] and diabetes [3.33 (1.70-6.53)] remained significant predictors of the cardiovascular outcome, whereas lnAng-2 did not enter the model. Neither of the microvascular variables were an independent predictor of all-cause mortality and cardiovascular events. Among the functional and biochemical microvascular parameters PORHHA seems to improve cardiovascular risk assessment in CKD. Nevertheless the robustness of traditional risk factors seems to outweigh the role of microvascular biomarkers on all-cause mortality and cardiovascular events at this time.

The Mediterranean Diet Score Is More Strongly Associated with Favorable Cardiometabolic Risk Factors over 2 Years Than Other Diet Quality Indexes in Puerto Rican Adults

BackgroundMultiple diet quality scores have been used to evaluate adherence to specific dietary recommendations or to consumption of healthful foods and nutrients. It remains unknown which score can more strongly predict longitudinal changes in cardiometabolic risk factors. ObjectiveWe aimed to determine associations of 5 diet quality scores [AHA diet score (AHA-DS), Dietary Approaches to Stop Hypertension (DASH), Healthy Eating Index (HEI)-2005, Mediterranean diet score (MeDS), and Alternative Healthy Eating Index (AHEI)] with 2-y changes in cardiometabolic risk factors in adults 45–75 y old. MethodsData from the Boston Puerto Rican Health Study were analyzed (n = 1194). Diet quality scores were calculated from a baseline-validated food-frequency questionnaire. Multivariable-adjusted, repeated-subjects, mixed-effects models, adjusted for baseline measures, estimated associations between each z score and 14 individual cardiometabolic factors measured at 2 y. ResultsMeDS was significantly associated with lower 2-y waist circumference (β coefficient ± SE: −0.52 ± 0.26, P = 0.048); body mass index (BMI; −0.23 ± 0.08, P = 0.005); log-insulin (−0.06 ± 0.02, P = 0.005); log–homeostasis model assessment of insulin resistance (HOMA-IR; −0.05 ± 0.02, P = 0.030), and log–C-reactive protein (−0.13 ± 0.03, P = 0.0002). Similar but weaker associations were observed for the AHEI with BMI, insulin, and HOMA-IR. The AHA-DS was inversely associated with BMI (−0.17 ± 0.08, P = 0.033). Neither the HEI-2005 nor DASH was significantly associated with any variable. Traditional Puerto Rican foods consumed by individuals with high MeDSs included vegetables and meats in homemade soups, orange juice, oatmeal, beans and legumes, fish, whole milk, corn oil, and beer. ConclusionsThe MeDS comprises food components and scores associated with a favorable cardiometabolic profile over 2 y in Puerto Rican adults. An overall healthy diet may be particularly beneficial for maintaining a lower BMI. These results can help identify suitable measures of diet quality in epidemiologic studies and craft meaningful nutritional messages and dietary recommendations for the intended population. This study was registered at clinicaltrials.gov as NCT01231958.

SEVERE CHRONIC PERIODONTITIS AND C-REACTIVE PROTEIN LEVELS

This study aims to analyze the relationship between chronic periodontitis and C-reactive protein (CRP), taking certain associated factors into consideration. A cross-sectional study was conducted on a sample of 75 adults of both sexes. After the participants had been interviewed, they underwent physical and dental examinations and blood collection. CRP levels were evaluated by means of nephelometry. A periodontal clinical examination was conducted by trained examiners and the diagnosis of chronic periodontitis was established when at least 30% of the individual’s teeth presented clinical attachment loss ≥ 5 mm. The analysis procedures consisted of descriptive analysis and linear regression. The results showed that there was no statistically significant difference in CRP levels between the groups with and without periodontitis. The median CRP level in the group with periodontitis was 2.3 mg/l (25-75% interquartile range, IQR = 0.74-5.4) and in the group without periodontitis, 1.8 mg/l (25-75% IQR = 0.79-4.54) (p = 0.417). Log CRP was significantly correlated only with the individual’s body mass index (BMI). The main findings from this study indicate that there is no association between severe chronic periodontitis and CRP, and factors like BMI need to be analyzed carefully in studies on this topic.