Measurements Of High-sensitivity C-reactive Protein Research Articles

Lack of Immune Resilience Negatively Affects Physical Resilience: Results From the InCHIANTI Follow-Up Study.

There is consistent evidence that immune response declines with aging, with wide interindividual variability and a still unclear relationship with the development of frailty. To address this question, we assessed the role of immune resilience (capacity to restore immune functions), operationalized as the neutrophil-to-lymphocytes ratio (NL-ratio) and monocytes-to-lymphocytes ratio (ML-ratio), in the pathway that from robust status shifts to pre-frailty and frailty, and finally to death. The InCHIANTI study enrolled representative samples from the registry lists of 2 towns in Tuscany, Italy. Baseline data were collected in 1998, with follow-up visits every 3 years. The 1453 participants enrolled were assessed and followed for lifestyle, clinical condition, physical performance, clinical, and physiological measures. For the purpose of this analysis, we used only 1022 subjects aged 65 or older at baseline. Participants in the 3 highest deciles of distribution for NL-ratio (>2.44) were more likely to experience a transition from robust to pre-frail, and to overt frailty status. Moreover, NL-ratio (tenth decile > 3.53) and ML-ratio (tenth decile > 2.02) were both predictors of mortality. These results were independent of chronological age, sex, comorbidities, and chronic low-grade inflammation assessed by high sensitivity C-reactive protein measurement. The 2 leucocytes-derived ratios, NL-ratio and ML-ratio, represent markers of immune resilience and predict changes in physical resilience and mortality. These biomarkers are inexpensive because they are based on data routinely collected in clinical practice and can be used to assess the risk of frailty progression and mortality. Clinical Trials Registration Number: NCT01331512.

Retinal changes and cardiac biomarker assessment in relation to chronic kidney disease: a single centre study

BackgroundThe prevalence of chronic kidney disease (CKD) is rising in Malaysia. Early detection is necessary to prevent disease progression, especially in terms of cardiovascular (CV) risk, the main cause of death in end-stage renal disease (ESRD). Retinal changes have proven to be a good predictor of CKD whereas cardiac biomarkers are useful in cardiovascular risk stratification. We aimed to demonstrate the correlation between retinal changes and cardiac biomarkers with CKD.MethodsThis single-centre cross-sectional study was conducted among patients with CKD stages 3, 4, and 5 (not on dialysis) from the Nephrology Clinic, Universiti Kebangsaan Malaysia Medical Centre. A total of 84 patients were recruited with an even distribution across all three stages. They underwent fundus photography where images were analysed for vessel calibre (central retinal venular equivalent (CRVE), central retinal arterial equivalent (CRAE), and tortuosity indices. Optical coherence tomography was used to measure macular volume. Blood samples were sent for laboratory measurement of high-sensitivity C-reactive protein (hs-CRP) and asymmetric dimethylarginine (ADMA). These parameters were analysed in relation to CKD.ResultsThe mean age was 58.8 ± 11.7 years, with 52.4% male and 47.6% female patients. Among them, 64.3% were diabetics. Retinal vessel tortuosity (r = -0.220, p-value = 0.044) had a negative correlation with the estimated glomerular filtration rate (eGFR). CRVE showed a positive correlation with proteinuria (r = 0.342, p = 0.001) but negative correlation with eGFR (r = -0.236, p = 0.031). Hs-CRP positively correlated with proteinuria (r = 0.313, p = 0.04) and negatively correlated with eGFR (r = -0.370, p = 0.001). Diabetic patients had a higher CRVE compared to non-diabetic patients (p = 0.02). History of ischaemic heart disease was associated with a smaller macula volume (p = 0.038). Male gender (r2 = 0.066, p = 0.031) and HbA1c had a positive influence (r2 = 0.066, p = 0.047) on retinal vessel tortuosity. There was a positive influence of age (r2 = 0.183, p = 0.012) and hs-CRP (r2 = 0.183, p = 0.045) on CRVE. As for macula volume, it negatively correlated with diabetes (r2 = 0.015, p = 0.040) and positively correlated with smoking (r2 = 0.015, p = 0.012).ConclusionOur study showed that eGFR value affects retinal vessel tortuosity, CRVE and hs-CRP. These parameters bear potential to be used as non-invasive tools in assessing CKD. However, only macula volume may be associated with CVD risk among the CKD population.

Medium term moderate to low-level air pollution exposure is associated with higher C-reactive protein among healthy Danish blood donors

Air pollution is a significant contributor to the global burden of disease with a plethora of associated health effects such as pulmonary and systemic inflammation. C-reactive protein (CRP) is associated with a wide range of diseases and is associated with several exposures. Studies on the effect of air pollution exposure on CRP levels in low to moderate pollution settings have shown inconsistent results.In this cross-sectional study high sensitivity CRP measurements on 18,463 Danish blood donors were linked to modelled air pollution data for NOx, NO2, O3, CO, SO2, NH3, mineral dust, black carbon, organic carbon, sea salt, secondary inorganic aerosols and its components, primary PM2.5, secondary organic aerosols, total PM2.5, and total PM10 at their residential address over the previous month. Associations were analysed using ordered logistic regression with CRP quartile as individuals outcome and air pollution exposure as scaled deciles. Analyses were adjusted for health related and socioeconomic covariates using health questionnaires and Danish register data.Exposure to different air pollution components was generally associated with higher CRP (odds ratio estimates ranging from 1.11 to 1.67), while exposure to a few air pollution components was associated with lower CRP. For example, exposure to NO2 increased the odds of high CRP 1.32-fold (95%CI 1.16–1.49), while exposure to NH3 decreased the odds of high CRP 0.81-fold (95%CI 0.73–0.89).This large study among healthy individuals found air pollution exposure to be associated with increased levels of CRP even in a setting with low to moderate air pollution levels.

Jia-Wei-Si-Miao-Yong-An decoction modulates intestinal flora and metabolites in acute coronary syndrome model.

We assessed the efficacy of the traditional Chinese medicine formulation Jia-Wei-Si-Miao-Yong-An decoction (HJ11) in the treatment of acute coronary syndrome and evaluated its impact on the intestinal microbiota and their metabolites. An acute coronary syndrome model was established in rats, which were randomly assigned to the model, HJ11 treatment, and atorvastatin treatment groups. Rats were then administered saline solution (model and sham operation control groups) or drugs by oral gavage for 28 d. Echocardiography was performed and serum creatine kinase-MB and cardiac troponin I levels were monitored to examine the cardiac function. Inflammation was evaluated using hematoxylin and eosin staining of heart tissue, and serum interleukin-2, interleukin-6, tumor necrosis factor alpha, and high-sensitivity C-reactive protein measurements. Gut microbiota composition was analyzed via 16S rRNA gene sequencing. Metabolomics was used to determine fecal metabolites and elucidate the modes of action of HJ11 in acute coronary syndrome treatment. HJ11 improved cardiac function and attenuated inflammation in rats with acute coronary syndrome. Relative to the untreated model group, the HJ11-treated group presented normalized Firmicutes/Bacteroidetes ratio and reduced abundances of the bacterial genera norank_f__Ruminococcaceae, Desulfovibrio, Clostridium_sensu_stricto_1, Adlercreutzia, Staphylococcus, Bacteroides, Prevotella, Rikenellaceae_RC9_gut_group, unclassified_o__Bacteroidales, and Ruminococcus_gauvreauii_group. We found 23 differentially expressed intestinal metabolites, and the enriched metabolic pathways were mainly related to amino acid metabolism. We also discovered that asymmetric dimethylarginine levels were strongly associated with cardiovascular disease. Correlation analyses revealed strong associations among intestinal microflora, their metabolites, proinflammatory factors, and cardiac function. Hence, the therapeutic effects of HJ11 on acute coronary syndrome are related to specific alterations in gut microbiota and their metabolites. This work demonstrated that HJ11 effectively treats acute coronary syndrome. HJ11 seems to increase the abundance of beneficial bacterial taxa (Bacteroides and Rikenellaceae_RC9_gut_group), mitigate the risk factors associated with cardiovascular disease, alter bacterial metabolites, lower asymmetric dimethylarginine levels, and effectively treat acute coronary syndrome.

Хроническая сердечная недостаточность с сохраненной фракцией выброса на фоне предиабета и абдоминального ожирения: компартменты жировых депо и кардиометаболические маркеры

Aim: to assess the fat depot compartments and some cardiometabolic risk markers in patients with chronic heart failure with preserved ejection fraction (CHFpEF), prediabetes and abdominal obesity. Patients and Methods: this randomized open single-center study was carried out in the Research Institute for Therapy and Preventive Medicine — Branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the RAS and included 64 subjects (32 of them were males) with CHFpEF, prediabetes and abdominal obesity. The standard general clinical examination and laboratory tests, measurements of NT-proBNP and high-sensitivity C-reactive protein (CRP) in blood plasma, as well as ultrasonography for imaging epicardial and preperitoneal fat depots (lipometry) were used to evaluate patients. Results: median age of the studied male patients was 58.00 [54.25; 60.00] years, female patients — 58.00 [56.00; 59.00] years. Males had a higher body weight as compared to females (р=0.036). The level of NT-proBNP in women was lower than in men (p=0.036), just as the glomerular filtration rate (р=0.034). The thickness of the epicardial and preperitoneal fat layers were similar in men and women, while the subcutaneous fat layer was thicker in women (р=0.001). Male patients with grade 3 obesity had the lowest NT-proBNP concentration in blood plasma. In women with grade 2 and 3 obesity the concentration of high-sensitivity C-reactive protein (CRP) in blood plasma was higher than in women with overweight and grade 1 obesity (р=0.047). A moderate linear relationship between NT-proBNP and high-sensitivity CRP levels was found in female patients (r=0.375, p=0.034). Conclusion: body weight measurements, glomerular filtration rates and NT-proBNP concentrations in blood plasma were higher in the studied sample of men as compared to those in women. Male patients with grade 3 obesity had the minimal NT-proBNP level (just slightly above the diagnostic limit). The highest high-sensitivity CRP measurements were reported in women with grade 2 and 3 obesity which underscores their proinflammatory status. No significant differences in the visceral epicardial and preperitoneal fat compartments were found between male and female patients. KEYWORDS: chronic heart failure with preserved ejection fraction, prediabetes, obesity, NT-proBNP, C-reactive protein, epicardial fat, premesenteric fat, subcutaneous fat, males, females. FOR CITATION: Tsygankova O.V., Evdokimova N.E., Latyntseva L.D. Chronic heart failure with preserved ejection fraction amid prediabetes and abdominal obesity: fat depot compartments and cardiometabolic risk markers. Russian Medical Inquiry. 2023;7(1):22–29 (in Russ.). DOI: 10.32364/2587-6821-2023-7-1-22-29.

Association of leukocyte mitochondrial DNA copy number with longitudinal C-reactive protein levels and survival in older adults: a cohort study.

Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk. This prospective cohort study included 3928 adults aged ≥ 55years without systemic inflammation in the baseline examination of the Healthy Aging Longitudinal Study in Taiwan, which started in 2009. Each participant received leukocyte mitochondrial DNA copy number measurement using a fluorescence-based quantitative polymerase chain reaction at baseline, serum high-sensitivity C-reactive protein measurements at baseline and the follow-up examination five years later, and the ascertainment of all-cause death (until November 30, 2021). The relationships among the leukocyte mitochondrial DNA copy number, longitudinal serum high-sensitivity C-reactive protein levels, and time to all-cause mortality were examined using the joint longitudinal and survival modeling analysis. Of the 3928 participants (mean age: 69years; 2060 [52%] were women), 837 (21%) died during follow-up. In the adjusted analysis, one standard deviation lower natural log-transformed baseline leukocyte mitochondrial DNA copy number was associated with an increase of 0.05 (95% confidence interval [CI], 0.02 to 0.08) standard deviation in serum high-sensitivity C-reactive protein in subsequent years. An increase of 1 standard deviation in instantaneous high-sensitivity C-reactive protein levels was associated with a hazard ratio (HR) for all-cause mortality of 1.22 (95% CI, 1.14 to 1.30). Similar results were obtained after further adjusting for baseline high-sensitivity C-reactive protein levels (HR [95% CI], 1.27 [1.16 to 1.38]) and after excluding those with serum high-sensitivity C-reactive protein above 10mg/L (HR [95% CI], 1.21[1.11 to 1.31]) or 3mg/L (HR [95% CI], 1.19 [1.06 to 1.31]) during follow-up. A lower leukocyte mitochondrial DNA copy number was associated with persistently higher high-sensitivity C-reactive protein levels. Moreover, these higher time-varying high-sensitivity C-reactive protein levels were instantaneously associated with a higher risk of death.

Effect of BNT162b2 mRNA booster vaccination on VO2 max in recreational athletes: A prospective cohort study.

The goal of the present study was to systematically evaluate the effect of a booster vaccination with the BNT162b2 messenger RNA (mRNA;Pfizer-BioNTech®) vaccine on maximum oxygen uptake (VO2 max), potential signs of (peri)myocarditis, and sports participation. Recreational athletes who were scheduled to undergo booster vaccination were evaluated with transthoracic echocardiography, serum measurements of high-sensitivity C-reactive protein(hsCRP) and high-sensitivity troponin I, and a bicycle cardiopulmonary exercise test (CPET) with serum lactate evaluation before the booster vaccine administration. Sevendays postvaccination the test battery was repeated. Additionally, the subjects were asked to fill in a questionnaire on side effects and a subjective evaluation of their relative training volume and intensity as compared to the weeks before vaccination. A group of 42 analysed athletes showed a statistically significant 2.7% decrease in VO2 max after vaccination (mean standard error of mean pre: 48.6 (1.4) ml/kg/min; post: 47.3 (1.4) ml/kg/min; p = 0.004). A potentially clinically relevant decrease of 8.6% or more occurred in 8 (19%) athletes. Other CPET parameters and lactate curves were comparable. We found no serological or echocardiographic evidence of (peri)myocarditis. A slight but significant increase in hsCRP was noted 1 week after vaccination. Side effects were mild and sports participation was generally unchanged or mildly decreased after vaccination. In our population of recreational endurance athletes, booster vaccination with the BNT162b2 mRNA vaccine resulted in a statistically significant decrease in VO2max 7 days after vaccination. The clinical impact hereof needs to be further determined. No major adverse events were observed.

Prognostic implication of residual inflammatory risk according to disease status in patients treated with percutaneous coronary intervention

Abstract Background Compared with stable angina, acute myocardial infarction (AMI) phenotype is related with the elevated inflammatory activity. However, time-dependent change of inflammatory level and its prognostic implication has not been fully understood according to the disease entity. Methods We enrolled total 4,263 patients who underwent percutaneous coronary intervention (PCI) with serial measurement of high-sensitivity C-reactive protein (hsCRP) at on-admission and 1-month post-PCI. The risks of MACE (a composite of death, MI or stroke), and major bleeding were evaluated up to 4 years after procedure. Results Compared with the non-AMI group (n=1,887), the AMI group (n=2,376) showed the significant decrease of hs-CRP during 1 month (∇0.5 vs. ∇0.1 mg/L; P<0.001). However, 1-month hs-CRP value still was higher in the AMI group than in the non-AMI group (median: 1.0 vs. 0.9 mg/L; P=0.001). During 1-month follow-up, high vs. low inflammatory risk (upper vs. lower tertile of hs-CRP) was significantly associated with increased rate of MACE in the AMI group (HR: 7.66; 95% CI: 2.29–25.59; P<0.001), but not in the non-AMI group (HR: 0.74; 95% CI: 0.12–4.40; P=0.736). From 1-month to 4-years, patients with high inflammatory risk showed the greater rate of MACE compared to those with low inflammatory risk, in both the AMI (HR: 2.40; 95% CI: 1.73–3.45; P<0.001) and non-AMI (HR: 2.67; 95% CI: 1.80–3.94; P<0.001) groups. Conclusion In PCI-treated patients, patients presented with AMI showed the greater values of inflammatory activity and its prognostic implication during the early phase, but combined inflammatory risk appeared similar across the disease entity during the late phase. This result may support that clinical benefit of post-PCI anti-inflammatory treatment would be constant regardless of the disease entity during the stabilized phase. Funding Acknowledgement Type of funding sources: None.

Combined impact of residual inflammatory risk and chronic kidney disease on long-term clinical outcomes in patients undergoing percutaneous coronary intervention

BackgroundInflammatory status is associated with cardiovascular events in patients with coronary artery disease (CAD) and renal function impairment. Chronic kidney disease (CKD) increases the incidence of cardiovascular events. However, whether the presence of residual inflammatory risk (RIR) and CKD together has a synergistic effect on the long-term clinical outcomes of patients with stable CAD undergoing percutaneous coronary intervention (PCI) remains unclear. MethodsWe assessed 2,948 consecutive patients with stable CAD who underwent the first PCI from 2000 to 2016. Of these, we analyzed the data of patients (2,087) with measurements of high-sensitivity C-reactive protein (hs-CRP) available at follow-up (6–9 months later). High RIR was defined as hs-CRP of >0.6 mg/L according to the median value at follow-up. Patients were classified into four groups: Group 1 (low RIR, non-CKD), Group 2 (high RIR, non-CKD), Group 3 (low RIR, CKD), and Group 4 (high RIR, CKD). We evaluated all-cause mortality and major adverse cardiac events (MACE). The median follow-up period was 5.2 (interquartile range, 1.9–9.9) years. ResultsIn total, 189 (16.1%) and 128 (11.2%) cases of all-cause mortality and MACE, respectively, were identified during follow-up. The rates of all-cause mortality and MACE were significantly higher in Group 4 than those in the other groups (p<0.001). There was a stepwise increase in the incidence of all-cause mortality and MACE. Upon adjustment for important covariates, the presence of high RIR and/or CKD showed an independent association with a high incidence of MACE and all-cause mortality. ConclusionsThe presence of high RIR and CKD conferred a synergistic adverse effect on the long-term clinical outcomes of patients undergoing PCI.

Effect of continuous positive airway pressure therapy on exhaled nitric oxide and C-reactive protein as markers of inflammation in Egyptian patients with obstructive sleep apnea

Background Obstructive sleep apnea syndrome (OSAS) is associated with the respiratory tract inflammation. Fractional exhaled nitric oxide (FeNO) and high-sensitivity C-reactive protein (Hs-CRP) are indicators of airway and systemic inflammation. Few revisions have explored the effect of continuous positive airway pressure (CPAP) on both indicators in OSAS. Purpose To study the influence of CPAP therapy on exhaled NO and Hs-CRP in OSAS. Patients and methods This is a case–control study that included 27 participants with OSAS and 10 controls enlisted from a sleep outpatient clinic. Full-night polysomnography was performed, and the next morning, FeNO and Hs-CRP were evaluated. CPAP for patients with moderate to severe OSA was advised with measurement of FeNO and Hs-CRP after 3 months of CPAP. Results Both FeNO and Hs-CRP in patients with OSA were statistically significantly increased against the control group. However, after 3 months of CPAP therapy, there was a statistically significant decrease in both FeNO and Hs-CRP. Conclusion Upper airway and systemic inflammation are extant in OSAS, reinforced by increases in both FeNO and CRP, and CPAP therapy diminishes FeNO levels in patients with OSA.

Combined non-invasive scan and biomarkers to identify independent risk factors in patients with mild coronary stenosis

BackgroundIndependent risk factors for major adverse cardiovascular events (MACEs) in patients with mild coronary stenosis are uncertain. This study aims to investigate predictive biomarkers for MACEs in patients with mild coronary stenosis.MethodsTotally 381 patients with mild coronary stenosis were included and MACE incidences were recorded through a 24-month follow-up and 91 patients with unfavorable plaques characteristic are detected by CCTA. One unfavorable characteristic was recorded for 1 point and they were divided into three groups: high-risk group (HR, score =0), intermediate-risk group (IR, score =1) and low-risk group (LR, score/2). Specific blood biomarker measurements of high-sensitivity C-reactive protein (hs-CRP), matrix metallopeptidase 9 (MMP-9), and myeloperoxidase (MPO) were taken simultaneously.ResultsThe mean age, hs-CRP and MPO levels in the HR and IR group were significantly higher than that in the LR group. A considerably higher level of MMP-9 showed in the HR group compared to the LR group. The incidence rates of MACE were remarkably higher in HR group than LR group and IR group. Kaplan-Meier survival analysis demonstrated that the cumulative event—free survival rate of HR was significantly higher than that in LR and IR group and there was no significant difference between LR and IR group. The univariate COX regression analysis indicated that the age, hs-CRP, MPO, and unfavorable plaque scores ≥2 were independent risk factors for MACEs.ConclusionsHigh MPO levels were strongly correlated with MACEs in patients with mild coronary stenosis. Although confirmation is needed from larger trials, MPO could be a promising clinical tool to improve the risk stratification in patients with mild coronary stenosis and suggest strategies for the individualized prevention programs.

Impact of adenotonsillectomy on the evolution of inflammatory markers.

Tonsils are first-line host defence organs against pathogenic agents and participate in local and systemic immunity. Persistent increases in systemic inflammatory responses may contribute to associated morbidity. The aim of this study was to verify the short- and long-term impact of adenotonsillectomy on the evolution of inflammatory markers in 3- to 9-year-old children. A prospective and longitudinal study was conducted over 1year in 29 children who underwent tonsillectomy due to either chronic tonsillitis or adenotonsillar hypertrophy. Measurements of high-sensitivity C-reactive protein (hs-CRP) levels were taken. Levels of Th1-type cytokines [interleukin-1, interferon-γ, and tumor necrosis factor-α (TNF-α)] and anti-inflammatory Th2-type cytokines [interleukin-4, -5, -6, -10 and -13] were measured. Levels of transforming growth factor-beta (TGF-β) and intercellular adhesion molecule-1 (ICAM-1) were also determined. The results were compared to those of 29 control children. At baseline, children with surgery indications presented with higher levels of hs-CRP, interleukin-1 and -10, interferon-γ, TNF-αand ICAM-1, whereas values of interleukin-4 were significantly lower than in control children. Children with severe tonsillar obstruction had higher values of interleukin-1, -4, and -5 and lower values of interleukin-10 compared with children with recurrent tonsillitis. One year after surgery, the levels except IL-4 did not show a significant difference from those obtained in the control group. The levels of hs-CRP and TNF-αdecreased significantly in the first month. Children with chronic tonsillitis and/or adenotonsillar hypertrophy have significantly elevated levels of proinflammatory cytokines. Adenotonsillectomy restores the normal values of these parameters 1year after surgery.

Association of circulating proinflammatory marker, leucine‐rich‐α2‐glycoprotein (LRG1), following metabolic/bariatric surgery

Obesity confers substantial excess risk for morbidity and mortality, especially for type 2 diabetes (T2D). Leucine-rich-α2-glycoprotein 1 (LRG1), a novel proinflammatory factor, was recently reported to be higher in patients with T2D with complications of peripheral arterial disease. Association of LRG1, obesity, and weight loss is unknown. We examined whether plasma LRG1 is associated with obesity in health screening participants and if it predicts future weight loss in morbidly obese patients after metabolic/bariatric surgery. Cohort 1 was a cross-sectional study from a Health Screening program (n=616) in a tertiary hospital. Cohort 2 was a prospective study of morbidly obese patients (n=231) who underwent metabolic/bariatric surgery with follow-up weight measurements. Anthropometric data, baseline fasting glucose, plasma adiponectin, high sensitivity C-reactive protein (HsCRP), and LRG1 were measured. Postsurgery blood, after metabolic/bariatric surgery, were available for LRG1and HsCRP measurements in 57 patients. In the group with highest tertile of LRG1, body mass index (BMI), waist circumference, and HsCRP were significantly higher, while total cholesterol, high-density lipoprotein, low-density lipoprotein, and adiponectin were lower than tertiles 1 and 2. Generalized linear model analysis showed that female gender (P<.0001), non-Chinese ethnicity (P<.019), and higher HsCRP (P<.0001) levels were independent and significant determinants of higher plasma LRG1 levels. After adjustment for age, gender, ethnicity, and baseline BMI, female gender (P=.020), higher presurgery BMI (P=.001), and lower presurgery LRG1 (P=.002) remained statistically significant predictors for greater weight loss. Plasma LRG1 increased significantly [from 28.2 (21.9-36.8) to 34.9 (22.6-49.5)] μg/mL (P=.003) within 1.5months, after metabolic/bariatric surgery. Our study demonstrates that LRG1 level is positively associated with obesity and a lower level of plasma LRG1 predicts weight loss in metabolic/bariatric surgery. Our novel findings suggest LRG1, itself or in combination with other known factors, is a potential biomarker of inflammation and obesity.

Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study.

C-reactive protein (CRP) is a circulating biomarker indicative of systemic inflammation. We aimed to evaluate genetic associations with CRP levels among non-European-ancestry populations through discovery, fine-mapping and conditional analyses. A total of 30503 non-European-ancestry participants from 6 studies participating in the Population Architecture using Genomics and Epidemiology study had serum high-sensitivity CRP measurements and ∼200000 single nucleotide polymorphisms (SNPs) genotyped on the Metabochip. We evaluated the association between each SNP and log-transformed CRP levels using multivariate linear regression, with additive genetic models adjusted for age, sex, the first four principal components of genetic ancestry, and study-specific factors. Differential linkage disequilibrium patterns between race/ethnicity groups were used to fine-map regions associated with CRP levels. Conditional analyses evaluated for multiple independent signals within genetic regions. One hundred and sixty-three unique variants in 12 loci in overall or race/ethnicity-stratified Metabochip-wide scans reached a Bonferroni-corrected P-value <2.5E-7. Three loci have no (HACL1, OLFML2B) or only limited (PLA2G6) previous associations with CRP levels. Six loci had different top hits in race/ethnicity-specific versus overall analyses. Fine-mapping refined the signal in six loci, particularly in HNF1A. Conditional analyses provided evidence for secondary signals in LEPR, IL1RN and HNF1A, and for multiple independent signals in CRP and APOE. We identified novel variants and loci associated with CRP levels, generalized known CRP associations to a multiethnic study population, refined association signals at several loci and found evidence for multiple independent signals at several well-known loci. This study demonstrates the benefit of conducting inclusive genetic association studies in large multiethnic populations.

Impact of combined non-surgical and surgical periodontal treatment in patients with type 2 diabetes mellitus-a preliminary report randomized clinical study

Background/objectives: Scientific evidence regarding the effects of chronic periodontitis on Type 2 Diabetes Mellitus (T2M) is fragmentary and not definitive. This intervention study was designed to evaluate the effects of a Non-Surgical Procedure (NSP) in addition to a surgical procedure on systemic inflammation and glycaemic control in patients with T2M and periodontitis and Non-Diabetic (ND) patients with periodontitis. Material and Methods: A total of 100 patients with diabetes were randomly allocated to a treatment group and a control group. At least one tooth was extracted from each patient. After extraction, the control group (n=50) did not receive any other treatment until the 3-month follow-up. Patients in the treatment group (n=50) received Full-Mouth Scaling and Root Planing (FM-SRP).The Mean Probing Depth (MPD), Mean Attachment Level (MAL), Plaque Index (PI), Bleeding on Probing (BOP), fasting blood samples for the measurement of high-sensitivity C-Reactive Protein (hs-CRP), and glycated hemoglobin (HbA1c) were measured or taken at baseline and 3 months after treatment. To investigate the effect of diabetes on the therapeutic procedure’s outcome, ND patients with periodontitis (n=60) were divided into two equal groups and subjected to the same procedures and analysis. Results: HbA1c and hs-CRP decreased significantly in the diabetic groups and decreased more markedly when FM-SRP was added to tooth extraction (P<0.001). For ND patients, all of the examined periodontal parameters were in favor of the combination therapy (P<0.001). Conclusion: Non-surgical periodontal treatment can help improve the outcome of surgical periodontal procedures by reducing systemic inflammatory status and improve glucose metabolism.

Multimarker Assessment of Diastolic Dysfunction in Metabolic Syndrome Patients.

Metabolic syndrome (MetS) has been associated with left ventricular diastolic dysfunction (LVDD) with preserved systolic function. This study aims at identifying the predictive factors for LVDD in MetS patients. The studied group comprised 72 consecutive hospitalized patients (2010-2011) diagnosed with MetS based on AHA/NHLBI/IDF 2009 definition, free of cardiovascular disease (36.11% males, age 59.19 ± 5.26 years), who underwent echocardiographic examination. Laboratory measurements of high-sensitivity C-reactive protein (hs-CRP), fibrinogen (Fbg) and interleukin-6 (IL-6), 8-isoprostaglandin-F2alpa (8-isoPGF2α), uric acid, glutathione peroxidases, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured. LVDD was identified in 47 (65.27%) of the MetS patients. The diastolic blood pressure (DBP) was the strongest prediction factor for LVDD (areas under the receiver operating curve [AUC]: 0.73, odds ratios [OR]: 1.065). The number of MetS criteria was also significantly predictive for LVDD (AUC: 0.65, OR: 2.029, P < 0.04). IL-6, hs-CRP, Fbg, and NT-proBNP were predictive for LVDD when receiver operating curve (ROC) analyses were used. The multimarker model comprising age, sex, SBP and DBP, waist, circumference, triglycerides along with hs-CRP, IL-6, and NT-proBNP had the best predictive capacity (AUC: 0.88, P = 0.0001). In multivariate analysis, IL-6 remained an independent predictive biomarker for LVDD (OR: 2.045). Both MetS components and biomarkers of inflammation (IF) are predictive factors for LVDD. The best predictive multimarker model for LVDD in MetS patients is composed of waist, triglycerides (TGL), SBP, DBP, fasting glucose, IL-6, hs-CRP, and NT-proBNP. IL-6 remains an independent predictive biomarker for LVDD in MetS patients, underlining the importance of IF in the evolution of MetS to subclinical cardiac damage.

Satellite-based estimates of long-term exposure to fine particulate matter are associated with C-reactive protein in 30 034 Taiwanese adults.

BackgroundParticulate matter (PM) air pollution is associated with the risk of cardiovascular morbidity and mortality. However, the biological mechanism underlying the associations remains unclear. Atherosclerosis, the underlying pathology of cardiovascular disease, is a chronic inflammatory process. We therefore investigated the association of long-term exposure to fine PM (PM2.5) with C-reactive protein (CRP), a sensitive marker of systemic inflammation, in a large Taiwanese population.MethodsParticipants were from a large cohort who participated in a standard medical examination programme with measurements of high-sensitivity CRP between 2007 and 2014. We used a spatiotemporal model to estimate 2-year average PM2.5 exposure at each participant’s address, based on satellite-derived aerosol optical depth data. General regression models were used for baseline data analysis and mixed-effects linear regression models were used for repeated data analysis to investigate the associations between PM2.5 exposure and CRP, adjusting for a wide range of potential confounders.ResultsIn this population of 30 034 participants with 39 096 measurements, every 5 μg/m3 PM2.5 increment was associated with a 1.31% increase in CRP [95% confidence interval (CI): 1.00%, 1.63%) after adjusting for confounders. For those participants with repeated CRP measurements, no significant changes were observed between the first and last measurements (0.88 mg/l vs 0.89 mg/l, P = 0.337). The PM2.5 concentrations remained stable over time between 2007 and 2014.ConclusionsLong-term exposure to PM2.5 is associated with increased level of systemic inflammation, supporting the biological link between PM2.5 air pollution and deteriorating cardiovascular health. Air pollution reduction should be an important strategy to prevent cardiovascular disease.

PCV33 - High-Sensitivity C-Reactive Protein Measurements in Patients with a History of Myocardial Infarction: A Targeted Literature Review

PCV33 - High-Sensitivity C-Reactive Protein Measurements in Patients with a History of Myocardial Infarction: A Targeted Literature Review

Self-reported Mobility in Older Patients Predicts Early Postoperative Outcomes after Elective Noncardiac Surgery

Specific geriatric assessment tools may complement traditional perioperative risk stratification. The aim of this study was to evaluate whether self-reported mobility is predictive of postoperative outcomes in older patients undergoing elective noncardiac surgery. Patients aged 69 yr or older (n = 197) underwent (1) traditional risk assessments (American Society of Anesthesiologists physical status classification and Revised Cardiac Risk Index), (2) five-point frailty evaluation, (3) self-reported mobility assessment using the Mobility Assessment Tool-short form (range, 30.21 [poor] to 69.76 [excellent]), and (4) measurements of high-sensitivity C-reactive protein. Outcomes were postoperative complications, time to discharge, and nursing home placement (NHP). In the sample of this study (mean age, 75 ± 5 yr; 51% women), 72% had intermediate- or high-risk surgery. Median time to discharge was 3 days (interquartile range, 1 to 4 days). Thirty patients (15%) developed postoperative complications, and 27 (13%) required NHP. After controlling for age, sex, body mass index, pain score, Revised Cardiac Risk Index, American Society of Anesthesiologist physical status, surgical risk, and high-sensitivity C-reactive protein, worse self-reported mobility (per 10-point decrease in Mobility Assessment Tool, which is equivalent to 1 SD) was associated with more postoperative complications (odds ratio [OR], 1.69; 95% CI, 1.05 to 2.73), later time to discharge (hazards ratio, 0.81; 95% CI, 0.68 to 0.96), and increased NHP (OR, 2.01; 95% CI, 1.13 to 3.56). By using the same model, intermediate frailty or frailty increased NHP (OR, 3.11; 95% CI, 1.02 to 9.54) but was not related to either postoperative complications or time to discharge. Preoperative self-reported mobility using a novel and brief assessment may help identify elderly patients at risk for adverse postoperative events.

Circulating MicroRNA223 is a New Biomarker for Inflammatory Bowel Disease.

Endoscopy is an important tool in screening and monitoring inflammatory bowel disease (IBD); however, it is invasive, costly, and associated with risks to the patients. Recently, circulating microRNAs (miRNAs) have emerged as promising noninvasive biomarkers. We proposed that the expression of serum microRNA223 (miR-223) could be a biomarker for IBD.Studies were conducted using serum samples from 100 patients with IBD (50 with Crohn's disease [CD] and 50 with ulcerative colitis [UC]) and 50 healthy controls. The expression of serum miR-223 was measured by quantitative reverse transcription-polymerase chain reaction. The clinical disease activity was assessed by measurement of the Crohn's disease activity index for CD and the Mayo score for UC. Endoscopies were performed and graded according to the simple endoscopic score for CD and the ulcerative colitis endoscopic index of severity scores for UC. Blood samples for the measurement of high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were taken within 1 week before or after endoscopy.Serum miR-223 expression increased 2.2 times in patients with CD and 2.8 times in patients with UC compared with the control group. Most importantly, the level of serum miR-223 was correlated with several indicators of disease activity both in CD and UC. Serum miR-223 demonstrated a higher Spearman r value than ESR and hs-CRP in detecting the disease activity of patients with IBD.Serum miR-223 might be a promising biomarker for monitoring disease activity in IBD patients.