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Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Metabola bensjukdomar)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
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2011 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 31, no 1, 219-227 p.Article in journal (Refereed) Published
Abstract [en]

Objective—Disturbances in mineral metabolism define an increased cardiovascular risk in patients with chronic kidney disease. Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and has recently been implicated as a putative pathogenic factor in cardiovascular disease. Because other members of the FGF family play a role in lipid and glucose metabolism, we hypothesized that FGF23 would associate with metabolic factors that predispose to an increased cardiovascular risk. The goal of this study was to investigate the relationship between FGF23 and metabolic cardiovascular risk factors in the community.

Methods and Results—Relationships between serum FGF23 and body mass index (BMI), waist circumference, waist-to-hip ratio, serum lipids, and fat mass were examined in 2 community-based, cross-sectional cohorts of elderly whites (Osteoporotic Fractures in Men Study: 964 men aged 75±3.2; Prospective Investigation of the Vasculature in Uppsala Seniors study: 946 men and women aged 70). In both cohorts, FGF23 associated negatively with high-density lipoprotein and apolipoprotein A1 (7% to 21% decrease per 1-SD increase in log FGF23; P<0.01) and positively with triglycerides (11% to 14% per 1-SD increase in log FGF23; P<0.01). A 1-SD increase in log FGF23 was associated with a 7% to 20% increase in BMI, waist circumference, and waist-to-hip ratio and a 7% to 18% increase in trunk and total body fat mass (P<0.01) as determined by whole-body dual x-ray absorptiometry. FGF23 levels were higher in subjects with the metabolic syndrome compared with those without (46.4 versus 41.2 pg/mL; P<0.05) and associated with an increased risk of having the metabolic syndrome (OR per 1-SD increase in log FGF23, 1.21; 95% CI, 1.04 to 1.40; P<0.05).

Conclusion—We report for the first time on associations between circulating FGF23, fat mass, and adverse lipid metabolism resembling the metabolic syndrome, potentially representing a novel pathway(s) linking high FGF23 to an increased cardiovascular risk.

Place, publisher, year, edition, pages
2011. Vol. 31, no 1, 219-227 p.
Keyword [en]
cardiovascular disease prevention, diabetes mellitus, elderly, epidemiology, FGF-23, FGF23, Fibroblast growth factor-23, growth factors, lipids, metabolism
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-130337DOI: 10.1161/ATVBAHA.110.214619ISI: 000285342400033PubMedID: 20966399OAI: oai:DiVA.org:uu-130337DiVA: diva2:349334
Available from: 2010-09-06 Created: 2010-09-06 Last updated: 2014-11-12Bibliographically approved
In thesis
1. The role of fibroblast growth factor-23 in chronic kidney disease-mineral and bone disorder
Open this publication in new window or tab >>The role of fibroblast growth factor-23 in chronic kidney disease-mineral and bone disorder
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fibroblast growth factor-23 (FGF23) was initially identified as the causative factor of autosomal dominant hypophosphatemic rickets. Further studies confirmed that FGF23 is predominantly expressed in the osteocytes and osteoblasts of bone and that circulating FGF23 acts on the kidney to inhibit renal phosphate reabsorption and 1,25(OH)2D3 hydroxylation.

With the progression of chronic kidney disease (CKD), the kidneys become insufficient to maintain a normal systemic mineral homeostasis, resulting in various abnormalities of bone and mineral metabolism, generally referred to as Chronic Kidney Disease – Mineral and Bone Disorders (CKD-MBD). FGF23 increases early in the course of CKD in order to maintain normal serum phosphate levels; long before a significant increase in serum phosphate can be detected. Recent studies suggest that increased FGF23 levels are associated with progression of CKD, mortality, and the development of refractory secondary hyperparathyroidism. Because FGF23 is the very earliest marker of CKD-MBD, it is of particular interest to evaluate the relation between FGF23 and CKD-MBD abnormalities, in the setting of early CKD and also in individuals with normal renal function.

In the present work, we show that FGF23 is linked to several dynamic measurements of vascular function, including endothelial dysfunction, arterial stiffness, and atherosclerosis. FGF23 is also positively associated with left ventricular mass index and an increased risk of having left ventricular hypertrophy. All associations were independent of serum phosphate and were strengthened in subjects with diminished renal function. Furthermore, we found significant evidence for an association between higher FGF23 and increased fat mass and dyslipidemia, which could represent a novel pathway linking FGF23 to cardiovascular disease. Finally, we show that FGF23 is a significant predictor of future fracture risk.

Although these associations could be reflecting the increased risk associated with hyperphosphatemia and calcitriol deficiency, current evidence points towards FGF23 being more than an innocent bystander. At the very least, FGF23 holds promise of being a bio-marker of cardiovascular status and phosphate-related toxicity both in CKD and in the general population, and might be a therapeutic target that could improve the fatal prognosis in CKD patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 83 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 594
FGF23, FGF-23, CKD, CKD-MBD, cardiovascular disease, vascular function, atherosclerosis, hypertrophy, LVMI, LVH, fractures, bone, fat mass, obesity, apolipoproteins, cholesterol, lipids
National Category
Urology and Nephrology Cardiac and Cardiovascular Systems
Research subject
Medical Science
urn:nbn:se:uu:diva-130339 (URN)978-91-554-7883-4 (ISBN)
Public defence
2010-10-16, Grönwallsalen, Akademiska sjukhuset, ingång 70, Uppsala, 09:00 (English)
Available from: 2010-09-23 Created: 2010-09-06 Last updated: 2011-01-17Bibliographically approved

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