Complement C3 and C4, but not their regulators or activated products, are associated with incident metabolic syndrome: t
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ORIGINAL ARTICLE
Complement C3 and C4, but not their regulators or activated products, are associated with incident metabolic syndrome: the CODAM study Ying Xin1 Elisabeth Hertle1 Carla J. H. van der Kallen1 Casper G. Schalkwijk1 Coen D. A. Stehouwer1 Marleen M. J. van Greevenbroek 1 ●
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Received: 16 May 2018 / Accepted: 7 August 2018 © The Author(s) 2018
Abstract Purpose We investigated the associations of components of the alternative (C3, C3a, Bb, factor D [FD], factor H [FH], properdin) and the classical complement pathway (C4, C1q, C1-inhibitor [C1-INH]) with prevalent and incident metabolic syndrome in a cohort with a moderately increased risk of cardiometabolic disease. Methods The study cohort was comprised of 574 participants (61% men, age 59.6 ± 7.0 years) at baseline and 489 participants after 7-year follow-up. Multiple logistic regression analyses were done to investigate the associations of concentrations of baseline plasma complement (standardized values) with prevalent and incident (in those without metabolic syndrome at baseline, n = 189) metabolic syndrome. Results C3 (odds ratio (OR) = 1.48 [95% confidence interval: 1.02; 2.14]) and C4 (OR = 1.95 [1.32; 2.88]), but none of the other complement components were associated with incident metabolic syndrome (n = 40 cases). Notably, in the crosssectional analyses, we did observe higher levels of C3a (OR = 1.25 [1.03; 1.52]), FH (OR = 2.93 [2.24; 3.83]), and properdin (OR = 1.88 [1.50; 2.34]), in addition to C3 (OR = 3.60 [2.73; 4.75]) and C4 (OR = 1.39 [1.13; 1.69]), in those with the metabolic syndrome compared to those without, while no association was observed for FD, Bb, C1q, or C1-INH. Conclusions In the cross-sectional analyses, the effects sizes (standardized regression coefficients) for C3 and C4 were similar to those of (some of) the regulators and activators, yet only C3 and C4 were associated with incident disease. These findings suggest a role for C3 and C4, but not their regulators or activated products, in the development of the metabolic syndrome. Keywords Human Complement activation Metabolic syndrome Incidence Longitudinal ●
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Introduction The metabolic syndrome is a cluster of cardiovascular risk factors that is characterized by central obesity, dyslipidemia, hypertension, and insulin resistance. Obesity is one of the
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12020-018-1712-3) contains supplementary material, which is available to authorized users. * Marleen M. J. van Greevenbroek [email protected] 1
Department of Internal Medicine, Maastricht University Medical Centre and CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
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initial events in the pathological processes that define the metabolic syndrome [1]. Dysfunctional adipose tissue is considered an important driver in the development of the adverse metabolic profiles in people with obesity [1]. The complement syst
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