Relation of inflammatory marker trajectories with frailty and aging in a 20-year longitudinal study

AbstractLittle is known about the development of low-grade inflammation with age and its relationship with the onset of frailty. In this exploratory study, we investigated 18 inflammatory markers measured in blood of 148 individuals aged 65-75 years at study endpoint, collected over 20 years at five-year intervals. IFNγ- and platelet activation markers changed in synchrony over time. Chronically elevated levels of IL-6-related markers, such as CRP and sIL-6R, were associated with frailty and becoming frail over time,, poorer lung function or less physical strength. Overweight was a possible driver of these associations. More and stronger associations were detected in women, such as between increasing sCD14 levels and frailty, indicating possible monocyte overactivation. Multivariate prediction of frailty showed low accuracy but confirmed the main results. In summary, we documented 20-year temporal changes in and between inflammatory markers in an aging population, and related these to clinically relevant health outcomes.

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Abstract 5083: Body Composition, Cardiorespiratory Fitness and Low-Grade Inflammation in Middle-Aged Men and Women

Circulation ◽

10.1161/circ.118.suppl_18.s_1142-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Benoit J Arsenault ◽

Amelie Cartier ◽

Melanie Cote ◽

Isabelle Lemieux ◽

Angelo Tremblay ◽

...

Keyword(s):

Cardiorespiratory Fitness ◽

Inflammatory Markers ◽

Inflammatory Marker ◽

Fat Distribution ◽

Low Grade ◽

Middle Aged ◽

Men And Women ◽

Wide Range ◽

Low Grade Inflammation ◽

Inflammation Score

Background: Although low levels of cardiorespiratory fitness (CRF) and obesity are often associated with a deteriorated cardiometabolic risk profile including low-grade inflammation, the respective contributions of specific indices of body fat distribution and CRF to variation of inflammatory markers remains uncertain. We therefore sought to determine the respective contributions of visceral adipose tissue (VAT) accumulation and CRF to variation of inflammatory markers in middle-aged men and women. Methods and Results: A complete lipoprotein-lipid profile and circulating levels of inflammatory markers such as C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and adiponectin were obtained and in a sample of healthy men (n=120) and women (n=152) covering a wide range of obesity values. VAT accumulation was measured by computed tomography and CRF levels were measured by a progressive submaximal physical working capacity test. In both men and women, VAT was positively associated with CRP and IL-6 levels (r≥0.35, p<0.0001), negatively associated with adiponectin (r≤ −0.29, p≤0.0003), after adjusting for CRF. After adjusting for VAT, CRF was not associated with variation in inflammatory markers in women and only with adiponectin in men (r= −0.20, p=0.03). An inflammation score was developed based on the sex-specific 50 th percentile values of each inflammatory marker (0 or 1) which yielded a score ranging from 0 (low) to 4 (high). Participants who scored 0, 1 or 2 were considered as having a low score and participants who scored 3 or 4 had an elevated inflammation score. In participants with low VAT (<130cm 2 for men and <100cm 2 for women), the prevalence of participants with an elevated inflammation score was of 23.9% and of 28.0%, respectively for participants with high and low CRF, whereas in participants with an elevated VAT accumulation, the prevalence of an elevated inflammation score was of 60.0% and of 61.7%, respectively for high and low CRF. Conclusions: These results suggest that the inflammatory state associated with low CRF is largely attributable to the increased VAT accumulation often observed in poorly fit individuals.

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The Inflammation Network in the Pathogenesis of Erectile Dysfunction: Attractive Potential Therapeutic Targets

Current Pharmaceutical Design ◽

10.2174/1381612826666200424161018 ◽

2020 ◽

Vol 26 (32) ◽

pp. 3955-3972

Author(s):

Ecem Kaya-Sezginer ◽

Serap Gur

Keyword(s):

Erectile Dysfunction ◽

Endothelial Dysfunction ◽

Metabolic Diseases ◽

Inflammatory Marker ◽

Attractive Potential ◽

Common Denominator ◽

Low Grade ◽

Antiinflammatory Drugs ◽

Male Population ◽

Low Grade Inflammation

Background: Erectile dysfunction (ED) is an evolving health problem in the aging male population. Chronic low-grade inflammation is a critical component of ED pathogenesis and a probable intermediate stage of endothelial dysfunction, especially in metabolic diseases, with the inclusion of obesity, metabolic syndrome, and diabetes. Objective: This review will present an overview of preclinical and clinical data regarding common inflammatory mechanisms involved in the pathogenesis of ED associated with metabolic diseases and the effect of antiinflammatory drugs on ED. Methods: A literature search of existing pre-clinical and clinical studies was performed on databases [Pubmed (MEDLINE), Scopus, and Embase] from January 2000 to October 2019. Results: Low-grade inflammation is a possible pathological role in endothelial dysfunction as a consequence of ED and other related metabolic diseases. Increased inflammation and endothelial/prothrombotic markers can be associated with the presence and degree of ED. Pharmacological therapy and modification of lifestyle and risk factors may have a significant role in the recovery of erectile response through reduction of inflammatory marker levels. Conclusion: Inflammation is the least common denominator in the pathology of ED and metabolic disorders. The inflammatory process of ED includes a shift in the complex interactions of cytokines, chemokines, and adhesion molecules. These data have established that anti-inflammatory agents could be used as a therapeutic opportunity in the prevention and treatment of ED. Further research on inflammation-related mechanisms underlying ED and the effect of therapeutic strategies aimed at reducing inflammation is required for a better understanding of the pathogenesis and successful management of ED.

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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial

Gut ◽

10.1136/gutjnl-2017-314786 ◽

2017 ◽

Vol 68 (1) ◽

pp. 83-93 ◽

Cited By ~ 84

Author(s):

Henrik Munch Roager ◽

Josef K Vogt ◽

Mette Kristensen ◽

Lea Benedicte S Hansen ◽

Sabine Ibrügger ◽

...

Keyword(s):

Body Weight ◽

Insulin Sensitivity ◽

Gut Microbiome ◽

Inflammatory Markers ◽

Dietary Intervention ◽

Short Chain Fatty Acids ◽

Low Grade ◽

Whole Grain ◽

Intestinal Transit Time ◽

Low Grade Inflammation

ObjectiveTo investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality.Design60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed.Results50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye.ConclusionCompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation.Trial registration numberNCT01731366; Results.

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Lifestyle-related determinants of inflammation in adolescence

British Journal Of Nutrition ◽

10.1017/s0007114507839614 ◽

2007 ◽

Vol 98 (S1) ◽

pp. S116-S120 ◽

Cited By ~ 39

Author(s):

Julia Wärnberg ◽

Esther Nova ◽

Javier Romeo ◽

Luís A. Moreno ◽

Michael Sjöström ◽

...

Keyword(s):

Physical Activity ◽

Inflammatory Markers ◽

Large Scale ◽

Dietary Habits ◽

Epidemiological Studies ◽

Low Grade ◽

Inflammatory Processes ◽

Young Subjects ◽

Low Grade Inflammation ◽

Apparently Healthy

Inflammatory processes are involved in the pathogenesis of the most common chronic non-communicable diseases and may also play an important initiating role in their development. Only recently have inflammatory markers been included in epidemiological studies focusing on nutritional status, body composition and physical activity. We are just starting to understand how different lifestyles can determine basal levels of inflammatory biomarkers in early ages. This review aims to summarise what is known about the relationships between lifestyle-related determinants (focusing on overweight, physical activity and dietary habits) and inflammatory markers in apparently healthy young populations. Obesity is the most widely studied determinant. Several large-scale studies have now demonstrated that healthy young subjects with more body fat or higher BMI have moderately higher concentrations of inflammatory markers than their leaner peers, supporting the idea that obesity should be considered as a state of chronic low-grade inflammation. Less data is available to allow us to elucidate how physical activity/fitness or dietary patterns may have a direct effect on inflammation in apparently healthy, disease-free young populations.

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Betaine reduces the expression of inflammatory adipokines caused by hypoxia in human adipocytes

British Journal Of Nutrition ◽

10.1017/s0007114512000888 ◽

2012 ◽

Vol 109 (1) ◽

pp. 43-49 ◽

Cited By ~ 18

Author(s):

K. Olli ◽

S. Lahtinen ◽

N. Rautonen ◽

K. Tiihonen

Keyword(s):

Adipose Tissue ◽

Inflammatory Markers ◽

Mrna Level ◽

Low Grade ◽

Human Adipocytes ◽

Low Oxygen ◽

Hypoxic Conditions ◽

Tnf Α ◽

Oxygen Conditions ◽

Low Grade Inflammation

Obesity is characterised by a state of chronic low-grade inflammation and the elevated circulating and tissue levels of inflammatory markers, including inflammation-related adipokines, released from white adipose tissue. The expression and release of these adipokines generally rises as the adipose tissue expands and hypoxic conditions start to develop within the tissue. Here, the effect of betaine, a trimethylglycine having a biological role as an osmolyte and a methyl donor, on the expression of inflammation-related markers was tested in human adipocytes under hypoxia. Differentiated adipocytes were cultivated under low (1 %) oxygen tension for 8–20 h. The expression of different adipokines, including IL-6, leptin, PPARγ, TNF-α and adiponectin, was measured by quantitative PCR by determining the relative mRNA level from the adipocytes. Hypoxia, in general, led to a decrease in the expression of PPARγ mRNA in human adipocytes, whereas the expression levels of leptin and IL-6 mRNA were substantially increased by hypoxia. The cultivation of adipocytes under hypoxia also led to a reduction in the expression of TNF-α mRNA. The results showed that hypoxia increased the relative quantification of leptin gene transcription, and that betaine (250 μmol/l) reduced this effect, caused by low oxygen conditions. Under hypoxia, betaine also reduced the mRNA level of the pro-inflammatory markers IL-6 and TNF-α. These results demonstrate that the extensive changes in the expression of inflammation-related adipokines in human adipocytes caused by hypoxia can be diminished by the presence of physiologically relevant concentrations of betaine.

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A Consideration of Biomarkers to be Used for Evaluation of Inflammation in Human Nutritional Studies

British Journal Of Nutrition ◽

10.1017/s0007114512005119 ◽

2013 ◽

Vol 109 (S1) ◽

pp. S1-S34 ◽

Cited By ~ 154

Author(s):

P.C. Calder ◽

N. Ahluwalia ◽

R. Albers ◽

N. Bosco ◽

R. Bourdet-Sicard ◽

...

Keyword(s):

Inflammatory Markers ◽

Inflammatory Process ◽

Inflammatory Responses ◽

Task Force ◽

Inflammatory Marker ◽

Low Grade ◽

Future Health ◽

Modifying Factors ◽

Markers Of Inflammation ◽

Nutritional Studies

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.

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POST-COVID-19 SYNDROME, INFLAMMATORY MARKERS AND SEX DIFFERENCES

10.1101/2021.07.07.21260092 ◽

2021 ◽

Author(s):

MERYAM MAAMAR ◽

ARANCHA ARTIME ◽

EMILIO PARIENTE RODRIGO ◽

PATRICIA FIERRO ◽

YOLANDA RUIZ ◽

...

Keyword(s):

Neutrophil Count ◽

Inflammatory Markers ◽

Care Center ◽

Clinical Manifestations ◽

Low Grade ◽

Common Symptom ◽

Primary Care Center ◽

Neutrophil Lymphocyte Ratio ◽

Serum Crp ◽

Low Grade Inflammation

INTRODUCTION AND OBJECTIVE Post-COVID syndrome (PCS) is a poorly-known entity. Underlying low-grade inflammation (LGI) has been theorized as one of its pathophysiological mechanisms. We aimed to investigate a possible relationship between PCS and an increase in inflammation markers, in a sex-stratified analysis. PARTICIPANTS AND METHODS Mild cases of COVID-19 according to the WHO classification followed-up in a Primary Care Center, were included. We collected epidemiological data (age, sex, body mass index -BMI-, smoking, and comorbidities -Charlson index-), variables of the acute COVID-19 episode, and data at 3 months of follow-up (clinical manifestations and inflammatory markers). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase (LDH), ferritin, fibrinogen, and D-dimer levels were analyzed. Low-grade inflammation (LGI) was defined as serum CRP between >0.3 and <1.0 mg/dL. Five composite indices were built combining the upper ranges of 4 markers. Bivariate and multivariate analyses (logistic regression and general linear models) were performed, stratified by sex. RESULTS We analyzed 121 subjects with mild COVID-19 (56.2% women; mean age 46 years). The most common symptom in the acute episode was fever (60.3%), while it was fatigue in PCS (42.8%). Prevalence of PCS was 35.8% in women and 20.8% in men (p = 0.07). In women, after controlling for age, BMI, smoking, and comorbidities, the D1, D3, and D4 indices were consistently associated with PCS, with ORs of 5.14 (95% CI, 1.6-16.4), 4.20 (95% CI, 1.3- 13.3), and 4.12 (95% CI, 1.3-13.1), respectively; in patients with post-COVID anosmia and ageusia, neutrophils were significantly elevated (3.43 ± 0.3 vs 2.58 ± 0.1; p = 0.014, and 3.89 ±0.3 vs 2.59 ± 0.1; p = 0.002, respectively), after adjusting for confounders. In men, the D2 and D5 indices were associated with PCS, with adjusted ORs of 10.1 (95% CI, 1.2- 85) and 17.5 (95% CI, 2-153), respectively; furthermore, serum CRP in the LGI range was associated with PCS [adjusted OR=12.9 (95% CI, 1.3-121)], and in post-COVID persistent fatigue, the neutrophil count was significantly elevated (4.68 ± 0.6 vs 3.37 ± 0.1; p = 0.041), after controlling for confounders. CONCLUSIONS Consistent associations among PCS, anosmia, ageusia, and fatigue, with slight -but significant- elevated levels of inflammatory markers, have been observed. The neutrophil count was the most frequently involved marker. Sex-stratified analyses showed relevant differences between women and men concerning PCS and serum inflammatory markers.

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Lifestyle Measures to Reduce Inflammation

American Journal of Lifestyle Medicine ◽

10.1177/1559827611411646 ◽

2011 ◽

Vol 6 (1) ◽

pp. 4-13 ◽

Cited By ~ 6

Author(s):

Glenn A. Gaesser ◽

Siddhartha S. Angadi ◽

Dana M. Ryan ◽

Carol S. Johnston

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Aerobic Exercise ◽

Inflammatory Markers ◽

Dietary Factors ◽

Low Grade ◽

Inflammatory Status ◽

Anti Inflammatory ◽

Low Grade Inflammation

Chronic low-grade inflammation associated with cardiovascular disease and type 2 diabetes (T2D) may be ameliorated with exercise and/or diet. High levels of physical activity and/or cardiorespiratory fitness are associated with reduced risk of low-grade inflammation. Both aerobic and resistance exercise have been found to improve inflammatory status, with the majority of evidence suggesting that aerobic exercise may have broader anti-inflammatory effects. In particular, aerobic exercise appears to improve the balance between pro- and anti-inflammatory markers. Improvement in inflammatory status is most likely to occur in persons with elevated levels of pro-inflammatory markers prior to intervention. A number of dietary factors, including fiber-rich foods, whole grains, fruits (especially berries), omega-3 fatty acids, antioxidant vitamins (eg, C and E), and certain trace minerals (eg, zinc) have been documented to reduce blood concentrations of inflammatory markers. Anti-inflammatory foods may also help mitigate the pro-inflammatory postprandial state that is particularly evident after ingestion of meals high in saturated fat. Intensive lifestyle interventions involving both exercise and diet appear to be most effective. For the most part, anti-inflammatory effects of exercise and diet are independent of weight loss. Thus overweight and obese men and women, who are most likely to have a pro-inflammatory profile, do not necessarily have to normalize body mass index to improve inflammatory status and reduce risk of type 2 diabetes and cardiovascular disease.

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Biochemical Markers with Low-grade Inflammation as Predictors of Thrombotic Events in Antiphospholipid Syndrome

Revista de Chimie ◽

10.37358/rc.17.7.5722 ◽

2017 ◽

Vol 68 (7) ◽

pp. 1586-1590

Author(s):

Claudia Gavris ◽

Vladimir Poroch ◽

Laurentiu Simion ◽

Adrian Baracan ◽

Elena Toader ◽

...

Keyword(s):

Platelet Activation ◽

Antiphospholipid Syndrome ◽

Biochemical Markers ◽

Cumulative Risk ◽

Low Grade ◽

Activation Markers ◽

Acute Thrombosis ◽

Markers Of Inflammation ◽

Hs Crp ◽

Low Grade Inflammation

The study aimed to test the inflammation hypothesis in antiphospholipid syndrome (APS) by assessing biochemical markers of inflammation and platelet activation. Forty one patients with APS were compared to 40 controls. High-sensitivity C-reactive protein (hs-CRP) (as inflammatory biomarker), P-selectin and soluble CD40L (sCD40L) (as platelet activation markers) were measured by ELISA at enrolment and after 12 months follow-up. Serum hs-CRP, P-selectin and sCD40L levels were significantly higher in patients with APS compared to controls. P-selectin was significantly higher in APS patients with recurrent or acute thrombosis compared to APS patients with no recurrent thrombotic events. Serum hs-CRP and anticardiolipin antibodies (aCL) and were independent predictors of thrombosis in APS. In conclusion, persistent increased hs-CRP titres demonstrated low-grade inflammation in APS. Serum biomarkers as aCL and hs-CRP were independent thrombotic cumulative risk predictors in patients with APS.

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Dietary patterns and associations with biomarkers of inflammation in adults: a systematic review of observational studies

Nutrition Journal ◽

10.1186/s12937-021-00674-9 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Michael J. Hart ◽

Susan J. Torres ◽

Sarah A. McNaughton ◽

Catherine M. Milte

Keyword(s):

Systematic Review ◽

Dietary Patterns ◽

Inflammatory Markers ◽

Observational Studies ◽

Data Driven ◽

Low Grade ◽

Cross Sectional ◽

Inflammatory Status ◽

Anti Inflammatory ◽

Low Grade Inflammation

Abstract Background Evidence indicates that low-grade inflammation is involved in manychronic diseases of ageing. Modifiable lifestyle factors including dietcan affect low-grade inflammation. Dietary patterns allow assessment of the complex interactions of food nutrients and health and may be associated with inflammatory status. This systematic review aimed to summarises current evidence from observational studies for associations between dietary patterns and inflammatory biomarkers in the general adult population. This review followed the PRISMA guidelines. Methods We conducted a systematic search in Embase, CINAHL Complete, Global Health and MEDLINE complete databases. Search terms included terms for diet (“dietary patterns”, “diet scores”) and inflammation (“inflammation“, “c-reactive protein“, “interleukin“). Results The search produced 7161 records. Duplicates were removed leaving 3164 for screening. There were 69 studies included (60 cross-sectional, 9 longitudinal). Papers included studies that were: 1) observational studies; 2) conducted in community-dwelling adults over 18 years of age; 3) assessed dietary patterns; 4) measured specified biomarkers of inflammation and 5) published in English. Dietary patterns were assessed using diet scores (n = 45), data-driven approaches (n = 22), both a data-driven approach and diet score (n = 2). The most frequently assessed biomarkers were CRP (n = 64) and/or IL-6 (n = 22). Cross-sectionally the majority of analyses reported an association between higher diet scores (mostly Mediterranean and anti-inflammatory diet scores) and lower inflammatory markers with 82 significant associations from 133 analyses. Only 22 of 145 cross-sectional analyses using data-driven approaches reported an association between a dietary patterns and lower inflammatory markers; the majority reported no association. Evidence of an association between dietary patterns and inflammatory markers longitudinally is limited, with the majority reporting no association. Conclusions Adherence to healthy, Mediterranean and anti-inflammatory dietary scores, appear to be associated with lower inflammatory status cross-sectionally. Future research could focus on longitudinal studies using a potential outcomes approach in the data analysis. Trial registration PROSPERO Registration Number CRD42019114501.

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