A cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of Creactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but... Show moreA cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of Creactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but the potential longitudinal relationship has been less well studied. We aimed to examine whether basal and lipopolysaccharide (LPS-)induced levels of inflammatory markers are associated with anxiety symptom severity over the course of nine years. We tested the association between basal and LPS-induced inflammatory markers with anxiety symptoms (measured with the Beck's Anxiety Inventory; BAI, Fear Questionnaire; FQ and Penn's State Worry Questionnaire; PSWQ) at 5 assessment waves over a period up nine years. We used multivariate-adjusted mixed models in up to 2867 participants of the Netherlands Study of Depression and Anxiety (NESDA). At baseline, 43.6% of the participants had a current anxiety disorder, of which social phobia (18.5%) was most prevalent. Our results demonstrated that baseline inflammatory markers were significantly associated with several outcomes of anxiety at baseline over nine subsequent years. BAI subscale of somatic (arousal) symptoms of anxiety, and FQ subscale of agoraphobia demonstrated the strongest effects with standardized betacoefficients of up to 0.14. The associations were attenuated by 25%-30% after adjusting for the presence of (comorbid) major depressive disorder (MDD), but remained statistically significant. In conclusion, we found that participants with high levels of inflammatory markers have on average high levels of anxiety consisting of physical arousal and agoraphobia, which tended to persist over a period of nine years, albeit with small effect sizes. These associations were partly driven by co-morbid depression. Show less
Agrawal, R.; Testi, I.; Lee, C.S.; Tsui, E.; Blazes, M.; Thorne, J.E.; ... ; COVID-19 Imt Study Grp 2021
Background Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the... Show moreBackground Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the concerns related to IMT and the increased risk of infections, an urgent need for guidance on the management of IMT in patients with uveitis has emerged. Methods A cross-sectional survey of international uveitis experts was conducted. An expert steering committee identified clinical questions on the use of IMT in patients with NIU during the COVID-19 pandemic. Using an interactive online questionnaire, guided by background experience and knowledge, 139 global uveitis experts generated consensus statements for IMT. In total, 216 statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents and biologics in patients with NIU. Thirty-one additional questions were added, related to general recommendations, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine. Results Highest consensus was achieved for not initiating IMT in patients who have suspected or confirmed COVID-19, and for using local over systemic corticosteroid therapy in patients who are at high-risk and very high-risk for severe or fatal COVID-19. While there was a consensus in starting or initiating NSAIDs for the treatment of scleritis in healthy patients, there was no consensus in starting hydroxychloroquine in any risk groups. Conclusion Consensus guidelines were proposed based on global expert opinion and practical experience to bridge the gap between clinical needs and the absence of medical evidence, to guide the treatment of patients with NIU during the COVID-19 pandemic. Show less
The aim of this thesis was to unravel a selection of a multitude of potential causal pathways that may underlie the association between excess body fat and cardiovascular disease, such as... Show moreThe aim of this thesis was to unravel a selection of a multitude of potential causal pathways that may underlie the association between excess body fat and cardiovascular disease, such as adipokines, inflammation, HDL-cholesterol and postprandial triglyceride response, and cholesteryl ester transfer protein (CETP). We showed that hs-CRP and GlycA as measures of inflammation, adiponectin, and leptin are not associated with clinical and subclinical cardiovascular disease in the general population. However, all may be relevant markers of disease risk. Also, postprandial triglyceride excursions, genetically-determined CETP and HDL-cholesterol, while not related with subclinical atherosclerosis in the general population, may be interesting targets to pursue in women and men separately, and in subgroups of individuals at high-cardiovascular risk. Show less
Noordam, R.; Boersma, V.; Verkouter, I.; Cessie, S. le; Christen, T.; Lamb, H.J.; ... ; Mutsert, R. de 2020
Background and aims: In the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin... Show moreBackground and aims: In the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin resistance.Methods and results: In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, total body fat (TBF) was measured in all (n = 5772) participants who did not have missing data and neither used glucose-lowering medication, and abdominal subcutaneous adipose tissue (aSAT) and visceral adipose tissue (VAT) were assessed by MRI in a random subgroup (n = 2448). C-reactive protein (CRP), adiponectin, and leptin were considered as potential mediators, and insulin resistance was assessed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Mediation by CRP, adiponectin, and leptin was studied by including the mediators to the fully adjusted linear regression model. Participants had a mean (SD) age of 56 (6) years, TBF of 36 (9) %, VAT of 119 (61) cm2 and aSAT of 300 (111) cm2. Per SD of TBF, VAT and aSAT, HOMA-IR was 64% (95% confidence interval [CI]: 59-70), 33% (95% CI: 28-42) and 20% (95%CI: 14-26) higher, respectively. The association between aSAT and HOMA-IR fully disappeared after adjustment for leptin; the association between VAT and HOMA-IR attenuated after adjustment for leptin (22%) and adiponectin (15%). No mediation was observed by CRP, and mediation estimates were similar in men and women.Conclusion: Where leptin fully explained the aSAT-HOMA-IR association, the VAT-HOMA-IR association was only partly explained by leptin and adiponectin similarly in men and women. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. Show less
Minten, M.J.M.; Leseman-Hoogenboom, M.M.; Kloppenburg, M.; Kortekaas, M.C.; Leer, J.W.; Poortmans, P.M.P.; ... ; Ende, C.H.M. van den 2018
The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more... Show moreThe general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular disease, cognitive decline and cancer. For all analyses we used data of the participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We have shown that subjects carrying genetic variants coding for a high pro-inflammatory profile or a low anti-inflammatory profile have an increased risk to develop cardiovascular disease and cognitive decline. Moreover, they tend to have an increased risk of dying as a consequence of cancer. Furthermore we have provided first evidence that the process of epigenetics can play an important role in the patho-physiology of age-related diseases. Future research is necessary to investigate how we can corporate these results into clinical practice. For example, Anti-inflammatory and immunosuppressive mechanisms may be attractive targets for disease prevention and/or treatment. Show less
