scholarly journals DNA Methylation and Protein Markers of Chronic Inflammation and Their Associations With Brain and Cognitive Aging

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012997
Author(s):  
Eleanor L.S. Conole ◽  
Anna J. Stevenson ◽  
Susana Muñoz Maniega ◽  
Sarah E. Harris ◽  
Claire Green ◽  
...  

Objective:To investigate chronic inflammation in relation cognitive ageing by comparison of an epigenetic and serum biomarker of C-Reactive Protein and their associations with neuroimaging and cognitive outcomes.Methods:At baseline, participants (N = 521) were cognitively normal, around 73 years of age (M = 72.4, SD = 0.716), and had inflammation, vascular risk (cardiovascular disease history, hypertension, diabetes, smoking, alcohol consumption and BMI) and neuroimaging (structural and diffusion MRI) data available. Baseline inflammatory status was quantified by a traditional measure of peripheral inflammation – serum C-Reactive Protein (serum CRP) – and an epigenetic measure (DNA methylation signature of CRP; DNAm CRP). Linear models were used to examine the inflammation-brain health associations; mediation analyses were performed to interrogate the relationship between chronic inflammation, brain structure and cognitive functioning.Results:We demonstrate that DNAm CRP shows significantly (on average 6.4-fold) stronger associations with brain health outcomes than serum CRP. DNAm CRP is associated with total brain volume (β = -0.197, 95% CI [-0.28, -0.12], pFDR = 8.42 x 10-6), grey matter volume (β = -0.200, 95% CI [-0.28, -0.12], pFDR = 1.66 x 10-5) and white matter volume (β = -0.150, 95% CI [-0.23, -0.07], pFDR = 0.001) and regional brain atrophy. We additionally find that DNAm CRP has an inverse association with global and domain-specific (speed, visuospatial and memory) cognitive functioning, and that brain structure partially mediates this CRP-cognitive association (up to 29.7%), dependent on lifestyle and health factors.Conclusions:These results support the hypothesis that chronic inflammation may contribute to neurodegenerative brain changes which underlie differences in cognitive ability in later life and highlight the potential of DNA methylation proxies for indexing chronic inflammatory status.Classification of Evidence:This study provides Class II evidence that a DNA methylation signature of CRP levels is more strongly associated with brain health outcomes than serum CRP levels.

2020 ◽  
Author(s):  
Eleanor L.S. Conole ◽  
Anna J. Stevenson ◽  
Claire Green ◽  
Sarah E. Harris ◽  
Susana Muñoz Maniega ◽  
...  

AbstractLow-level chronic inflammation increases with age and is associated with cognitive decline. DNA methylation (DNAm) levels may provide more stable reflections of cumulative inflammatory burden than traditional serum approaches. Using structural and diffusion MRI data from 521 individuals aged 73, we demonstrate that a DNAm proxy of C-Reactive Protein (CRP) shows significantly (on average 6.4-fold) stronger associations with brain structural outcomes than serum CRP. We additionally find that DNAm CRP has an inverse association with global and domain-specific (speed, visuospatial and memory) cognitive functioning, and that brain structure partially mediates this CRP-cognitive association (up to 29.4%), dependent on lifestyle and health factors. These data support the hypothesis that chronic systemic inflammation may contribute to neurodegenerative brain changes which underlie differences in cognitive ability in later life. DNA methylation-based predictors could be used as proxies for chronic inflammatory status.


Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1042
Author(s):  
Yoo-Ra Cho ◽  
Ye-In Oh ◽  
Gun-Ho Song ◽  
Young Jun Kim ◽  
Kyoung-Won Seo

We performed this study to characterize the difference between the inflammatory and non-inflammatory status in diseased dogs by measuring salivary C-reactive protein (CRP) levels. In addition, we assessed whether a correlation exists between CRP levels in saliva and those in serum. CRP levels were measured in 32 client-owned dogs, which were then divided into inflammation and non-inflammation groups based on the serum CRP level. The salivary CRP level was higher in the inflammation group than in the non-inflammation group (p < 0.05). Furthermore, there was a positive correlation between the salivary and serum CRP levels (R = 0.866, p < 0.001). These data suggest that canine salivary CRP measurements can effectively and non-invasively detect an inflammatory state in dogs.


2011 ◽  
Vol 90 (12) ◽  
pp. 1411-1415 ◽  
Author(s):  
E. Ioannidou ◽  
H. Swede ◽  
A. Dongari-Bagtzoglou

Based on the existing evidence supporting a state of chronic inflammation in chronic kidney disease (CKD), we hypothesized that periodontal infection may affect the systemic inflammatory status of a nationally representative CKD population as measured by serum C-reactive protein (CRP). We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) dataset including 2303 individuals. We followed the American Academy of Periodontology (AAP)/Centers for Disease Control and Prevention (CDC) case definition for periodontitis. We used a cutoff point of 30% sites with (PD) ≥ 5 mm and (CAL) ≥ 4 mm to define generalized periodontitis cases. We estimated glomerular filtration rate based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on eGFR < 60 mL/min/1.73m2 and albuminuria ≥ 30 mg/g. Periodontitis was found in 427 (12.3%) individuals. Of individuals with periodontitis, 41.8% had serum CRP higher than 0.3 mg/dL compared with 27.1% of non-periodontitis and 53.1% of edentulous individuals (p = 0.001 for all comparisons). When the extent of periodontitis was used as one of the independent variables, the parsimonious model showed a strong independent association between extent of periodontitis and serum CRP levels (OR = 2.0, CI95% = 1.2-3.6).


2008 ◽  
Vol 27 (1) ◽  
pp. 35-39
Author(s):  
Olivera Dimitrijević ◽  
Blagica Đorić-Stojčevski ◽  
Svetlana Ignjatović ◽  
Nada Majkić-Singh

C-Reactive Protein in Estimating Inflammatory Status in Patients with Acute Coronary Syndrome Chronic inflammation plays a key role in the pathogenesis of atherosclerosis, and is considered as a risk factor for the occurrence of acute coronary events, together with traditional risk factors such as age, smoking, hypercholesterolemia, diabetes mellitus and genetic predisposition. In this study, inflammatory status was estimated in patients with acute coronary syndrome. C-reactive protein, erythrocyte sedimentation rate and white blood cell count were measured at admission to the hospital in 25 patients with unstable angina pectoris and 31 patients with acute myocardial infarction, and compared with healthy control group (n = 59). C-reactive protein was the only parameter that differed significantly between all three groups (p < 0.0001), and patients with unstable angina had higher levels (median 7.28 mg/L) than patients with myocardial infarction (4.10 mg/L) and control group (1.07 mg/L). The obtained results show that levels of chronic inflammation in patients with acute coronary syndrome are significantly higher than baseline inflammation levels in a healthy population.


i-Perception ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 204166952110099
Author(s):  
Ingrid Ekström ◽  
Davide Liborio Vetrano ◽  
Goran Papenberg ◽  
Erika J. Laukka

Importance Olfactory deficits are common in aging and associated with several conditions linked to inflammation. A few studies suggest that increased concentration of pro-inflammatory biomarkers may be related to olfactory deficits, but these associations are understudied in population-based samples. Objective To investigate the association between serum concentrations of C-reactive protein (CRP) and olfactory identification level as well as rate of change in aging. Methods We included 1,721 participants (mean age 70.5 years; 61.9% female) with at least two olfactory assessments across the 12-year follow-up. Baseline level and change in odor identification were estimated with linear mixed models as a function of CRP levels, derived from blood plasma at baseline. Results Results indicated a negative dose–response association between CRP level and odor identification scores at baseline, after adjustment for demographic, cognitive, health, and lifestyle factors. CRP levels ranging between 11 and 20 mg/L were significantly related to lower olfactory ability (β = −0.811, 95% confidence interval [CI] [−1.503 to −0.118]; p = .022). Likewise, CRP values above 20 mg/L were related to lower olfactory scores, an association that approached statistical significance (β = −0.996, 95% CI [−2.045 to 0.054]; p = .063). We found no associations between CRP and olfactory change ( ps > .368). Sensitivity analyses showed that associations between CRP and olfaction were confined to younger participants (age ≤72 years) and men ( ps < .034). Conclusions Our findings suggest a negative association between serum CRP levels and olfactory identification ability in aging that may be dependent on age and sex.


Author(s):  
Doruk Akgün ◽  
Mats Wiethölter ◽  
Paul Siegert ◽  
Victor Danzinger ◽  
Marvin Minkus ◽  
...  

Abstract Introduction There is a paucity of literature regarding serum C-reactive protein (CRP) in the evaluation of a shoulder periprosthetic joint infection (PJI). The purpose of the current study was to establish cutoff values for diagnosing shoulder PJI and evaluate the influence of the type of infecting microorganism and the classification subgroups according to last proposed International Consensus Meeting (ICM) criteria on the CRP level. Materials and methods A retrospective analysis of all 136 patients, who underwent septic or aseptic revision shoulder arthroplasty in our institution between January 2010 and December 2019, was performed. Shoulder PJI was defined according to the last proposed definition criteria of the ICM. Serum CRP levels were compared between infected and non-infected cases, between infection subgroups, as well as between different species of infecting microorganisms. A receiver-operating characteristic (ROC) analysis was performed to display sensitivity and specificity of serum CRP level for shoulder PJI. Results A total of 52 patients (38%) were classified as infected, 18 meeting the criteria for definitive infection, 26 for probable infection and 8 for possible infection. According to the ROC curve, an optimized serum CRP threshold of 7.2 mg/l had a sensitivity of 69% and specificity of 74% (area under curve = 0.72). Patients with definitive infection group demonstrated significantly higher median serum CRP levels (24.3 mg/l), when compared to probable, possible infection groups and PJI unlikely group (8 mg/l, 8.3 mg/l, 3.6 mg/l, respectively, p < 0.05). The most common isolated microorganism was Cutibacterium acnes in 25 patients (48%) followed by coagulase-negative staphylococci (CNS) in 20 patients (39%). Patients with a PJI caused by high-virulent microorganisms had a significantly higher median serum CRP level compared to patients with PJI caused by low-virulent microorganisms (48 mg/l vs. 11.3 mg/l, p = 0.04). Conclusions Serum CRP showed a low sensitivity and specificity for the diagnosis of shoulder PJI, even applying cutoffs optimized by receiver-operating curve analysis. Low-virulent microorganisms and patients with probable and possible infections are associated with lower CRP levels compared to patients with definitive infection and infections caused by high-virulent microorganisms. Level of evidence Diagnostic Level III.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Makrouhi Sonikian ◽  
Aggeliki Barbatsi ◽  
Eugenia Karakou ◽  
Theodoros Chiras ◽  
Jacob Skarakis ◽  
...  

Abstract Introduction C-reactive protein (CRP) and procalcitonin (PCT) are widely used as markers of inflammation and infection in general population and in chronic hemodialysis (HD) as well. However, in dialysis (D) patients, serum CRP and PCT levels may be elevated even in the absence of inflammatory or infectious disease and diagnostic process is a challenge in such cases. We studied HD patients' laboratory profile concerning CRP and PCT. Subjects and Methods We studied 25 stable HD patients, M/F=22/3, aged 68(44-89) years, dialyzed thrice weekly for 55(6-274) months with a dialysate flow rate of 700 ml/min, with a residual daily diuresis less than 200 ml, Kt/V values of 1,44±0,3 and no signs of infection. Patients were classified in two groups. Group A included 10 patients on pre-dilution online hemodiafiltration (HDF). Group B consisted of 15 patients on conventional HD with low-flux polysulfone membrane. Twenty healthy subjects formed a control group C. Serum CRP and PCT levels were measured in duplicate in A and B groups before and at the end of mid-week dialysis sessions and also in C group. Results Pre-D serum CRP values in the total of patients were higher than those in healthy controls (10,89±19,29 vs 2,54±1,28 mg/L-p=0,004). Compared with group C, pre-D CRP values were higher only in B group (15,98±24,54 mg/L-p=0,001) but not in A group (4,09±3,33 mg/L-p=NS). There was a significant difference in pre-D serum CRP values between A and B groups (p=0,028). At the end of D session serum CRP values showed a tendency to increase in both groups A (5,16±4,81 mg/L) and B (17,00±27,00 mg/L) but differences were not significant. Pre-D serum PCT values in the total of patients were higher than those in healthy controls (0,82±0,9 vs 0,29±0,55 ng/ml-p&lt;0,001). Compared with group C, pre-D PCT values were higher in both A group (0,52±0,15 ng/ml-p&lt;0,001) and B group (1,01±1,13 ng/ml-p=0,006). There was no significant difference in pre-D serum PCT values between A and B groups (p=0,261). At the end of D session serum PCT values decreased in A group (0,32±0,11 ng/ml-p&lt;0,001) and increased in B group (1,12±1,21 ng/ml-p=0,014). Conclusions In patients on both conventional low-flux HD and online HDF pre-D serum CRP and PCT levels were higher than those in healthy subjects. Dialysis modality and membrane flux did not affect post-D serum CRP values, but post-PCT values decreased in online HDF. PCT usefulness might be limited in dialysis with high-flux membranes. Cut-off values have to be established for both markers to eliminate confusion in diagnosis of inflammatory and infectious diseases in hemodialyzed patients.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Bonny Rockette-Wagner ◽  
Claudia Holzman ◽  
Bertha L Bullen ◽  
Andrew D Althouse ◽  
Janet M Catov

Introduction: Elevated serum C-reactive protein (CRP) can be a marker of disease activity involving inflammation, such as pregnancy complications and cardiovascular disease (CVD). Systemically high levels of CRP in women, including during pregnancy, may indicate higher risk for CVD. It is unknown if CRP measured during the pro-inflammatory state of pregnancy correlates with concentrations assessed 7-13 years after delivery. Hypothesis: Concentrations of CRP assessed during pregnancy will be related to CRP measured several years after pregnancy, independent of weight gain. Methods: We studied the first 252 women enrolled in the follow-up of the Pregnancy Outcomes and Community Health Study (POUCHmoms 2011-2013) with complete CRP data for the pregnancy (mean gestational age: 22.36 [2.22] weeks) and POUCHmoms visits (mean follow-up: 10.76 [1.38] years). The relative risk for high hsCRP (≥ 3.39 μg/ml) at the follow-up visit, related to quartiles of CRP during pregnancy, was examined using stepwise regression models. Results: Median (IQR) levels of pregnancy CRP and hsCRP at the follow-up visit were 5.68 [3.08, 9.76] and 3.39 [0.69, 9.73] μg/ml, respectively. Although absolute values of hsCRP at follow-up were generally lower than pregnancy CRP, 56% of women in the top and bottom quartiles of pregnancy CRP (71 of 126) were in the same quartile for hsCRP at follow-up (figure). The relative risk of having high hsCRP (≥ 3.39 μg/ml) at follow-up ranged from 2.7-5.2 for the 2 nd - 4 th quartiles of pregnancy CRP (vs. the 1st quartile). Controlling for pre-pregnancy BMI and follow-up weight change, the relative risk of having high hsCRP at follow-up was significantly higher for the 2 nd (1.15 [1.02-1.30]),3 rd (1.19 [1.05-1.35), and 4 th (1.22 [1.05-1.41]) quartiles of pregnancy CRP. Conclusions: Pregnancy CRP levels are related to hsCRP levels several years later in this cohort of women, even after adjusting for pre-pregnancy BMI and follow-up weight change. CRP assessed in pregnancy may reflect inflammatory status later in life.


2018 ◽  
Vol 100-B (11) ◽  
pp. 1482-1486 ◽  
Author(s):  
D. Akgün ◽  
M. Müller ◽  
C. Perka ◽  
T. Winkler

Aims The aim of this study was to determine the prevalence and characteristics of C-reactive protein (CRP)-negative prosthetic joint infection (PJI) and evaluate the influence of the type of infecting organism on the CRP level. Patients and Methods A retrospective analysis of all PJIs affecting the hip or knee that were diagnosed in our institution between March 2013 and December 2016 was performed. A total of 215 patients were included. Their mean age was 71 years (sd 11) and there were 118 women (55%). The median serum CRP levels were calculated for various species of organism and for patients with acute postoperative, acute haematogenous, and chronic infections. These were compared using the Kruskal–Wallis test, adjusting for multiple comparisons with Dunn’s test. The correlation between the number of positive cultures and serum CRP levels was estimated using Spearman correlation coefficient. Results Preoperative CRP levels were normal (< 10 mg/l) in 77 patients (35.8%) with positive cultures. Low-virulent organisms were isolated in 66 PJIs (85.7%) with normal CRP levels. When grouping organisms by species, patients with an infection caused by Propionibacterium spp., coagulase-negative staphylococci (CNS), and Enterococcus faecalis had significantly lower median serum CRP levels (5.4 mg/l, 12.2 mg/l, and 23.7 mg/l, respectively), compared with those with infections caused by Staphylococcus aureus and Streptococcus spp. (194 mg/l and 89.3 mg/l, respectively; p < 0.001). Those with a chronic PJI had statistically lower median serum CRP levels (10.6 mg/l) than those with acute postoperative and acute haematogenous infections (83.7 mg/l and 149.4 mg/l, respectively; p < 0.001). There was a significant correlation between the number of positive cultures and serum CRP levels (Spearman correlation coefficient, 0.456; p < 0.001). Conclusion The CRP level alone is not accurate as a screening tool for PJI and may yield high false-negative rates, especially if the causative organism has low virulence. Aspiration of the joint should be used for the diagnosis of PJI in patients with a chronic painful arthroplasty, irrespective of CRP level. Cite this article: Bone Joint J 2018;100-B:1482–86.


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