Fibroblast growth factor 23, mineral metabolism and mortality among elderly men (Swedish MrOs)

BMC Nephrology

Östen Ljunggren²  Torbjörn Linde²  Tobias E Larsson⁴  Claes Ohlsson⁵  Eric Orwoll³  Dan Mellström⁵  Magnus K Karlsson¹  Åsa Tivesten⁶  Per-Anton Westerberg⁷ 

[1] Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences and Orthopedic Surgery, Lund University, Skåne University Hospital, Lund, Sweden;Department of Medical Sciences, Uppsala University, Uppsala, Sweden;Oregon Health and Science University, Portland, OR, USA;Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden;Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden;Wallenberg Laboratory for Cardiovascular Research, University of Göteborg, Göteborg, Sweden;Department of Nephrology, Uppsala University, University hospital, Ing 30, 5 tr, Uppsala, SE-751 85, Sweden

关键词: Elderly;    Mortality;    Phosphatonin;    Mineral metabolism;    FGF23;    FGF-23;   

Others  :  1082953
DOI  :  10.1186/1471-2369-14-85

 received in 2013-01-02, accepted in 2013-03-26,  发布年份 2013

【 摘 要 】

Background

Fibroblast growth factor 23 (FGF23) is the earliest marker of disturbed mineral metabolism as renal function decreases. Its serum levels are associated with mortality in dialysis patients, persons with chronic kidney disease (CKD) and prevalent cardiovascular disease (CVD), and it is associated with atherosclerosis, endothelial dysfunction and left ventricular hypertrophy in the general population. The primary aim of this study is to examine the association between FGF23 and mortality, in relation to renal function in the community. A secondary aim is to examine the association between FGF23 and CVD related death.

Methods

The population-based cohort of MrOS Sweden included 3014 men (age 69–81 years). At inclusion intact FGF23, intact parathyroid hormone (PTH), 25 hydroxyl vitamin D (25D), calcium and phosphate were measured. Mortality data were collected after an average of 4.5 years follow-up. 352 deaths occurred, 132 of CVD. Association between FGF23 and mortality was analyzed in quartiles of FGF23. Kaplan-Meier curves and Log-rank test were used to examine time to events. Cox proportional hazards regression was used to examine the association between FGF23, in quartiles and as a continuous variable, with mortality. The associations were also analyzed in the sub-cohort with estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73 m².

Results

There was no association between FGF23 and all-cause mortality, Hazard ratio (HR) 95% confidence interval (CI): 1.02 (0.89-1.17). For CVD death the HR (95% CI) was 1.26 (0.99 - 1.59)/(1-SD) increase in log(10)FGF23 after adjustment for eGFR, and other confounders. In the sub-cohort with eGFR > 60 ml/min/1.73 m² the HR (95% CI) for CVD death was 55% (13–111)/(1-SD) increase in log(10)FGF23.

Conclusions

FGF23 is not associated with mortality of all-cause in elderly community living men, but there is a weak association with CVD death, even after adjustment for eGFR and the other confounders. The association with CVD death is noticeable only in the sub-cohort with preserved renal function.

【 授权许可】

   
2013 Westerberg et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Gutierrez O, Isakova T, Rhee E, Shah A, Holmes J, Collerone G, Juppner H, Wolf M: Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005, 16(7):2205-2215.
• [2]Westerberg PA, Linde T, Wikstrom B, Ljunggren O, Stridsberg M, Larsson TE: Regulation of fibroblast growth factor-23 in chronic kidney disease. Nephrol Dial Transplant 2007, 22(11):3202-3207.
• [3]Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT: Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010, 375(9731):2073-2081.
• [4]Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G: Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 2005, 112(17):2627-2633.
• [5]Hagstrom E, Hellman P, Larsson TE, Ingelsson E, Berglund L, Sundstrom J, Melhus H, Held C, Lind L, Michaelsson K, et al.: Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation 2009, 119(21):2765-2771.
• [6]Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutierrez OM, Steigerwalt S, He J, et al.: Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 2011, 305(23):2432-2439.
• [7]Mirza MA, Larsson A, Melhus H, Lind L, Larsson TE: Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis 2009, 207(2):546-551.
• [8]Gutierrez OM, Januzzi JL, Isakova T, Laliberte K, Smith K, Collerone G, Sarwar A, Hoffmann U, Coglianese E, Christenson R, et al.: Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 2009, 119(19):2545-2552.
• [9]Mirza MA, Hansen T, Johansson L, Ahlstrom H, Larsson A, Lind L, Larsson TE: Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transplant 2009, 24(10):3125-3131.
• [10]Mirza MA, Larsson A, Lind L, Larsson TE: Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 2009, 205(2):385-390.
• [11]Parker BD, Schurgers LJ, Brandenburg VM, Christenson RH, Vermeer C, Ketteler M, Shlipak MG, Whooley MA, Ix JH: The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the heart and soul study. Ann Intern Med 2010, 152(10):640-648.
• [12]Michaelsson K, Baron JA, Snellman G, Gedeborg R, Byberg L, Sundstrom J, Berglund L, Arnlov J, Hellman P, Blomhoff R, et al.: Plasma vitamin D and mortality in older men: a community-based prospective cohort study. Am J Clin Nutr 2010, 92(4):841-848.
• [13]Kilkkinen A, Knekt P, Aro A, Rissanen H, Marniemi J, Heliovaara M, Impivaara O, Reunanen A: Vitamin D status and the risk of cardiovascular disease death. Am J Epidemiol 2009, 170(8):1032-1039.
• [14]Semba RD, Houston DK, Bandinelli S, Sun K, Cherubini A, Cappola AR, Guralnik JM, Ferrucci L: Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr 2010, 64(2):203-209.
• [15]Flodin M, Jonsson AS, Hansson LO, Danielsson LA, Larsson A: Evaluation of gentian cystatin C reagent on abbott Ci8200 and calculation of glomerular filtration rate expressed in mL/min/1.73 m(2) from the cystatin C values in mg/L. Scand J Clin Lab Invest 2007, 67(5):560-567.
• [16]Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, et al.: Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008, 359(6):584-592.
• [17]Kendrick J, Cheung AK, Kaufman JS, Greene T, Roberts WL, Smits G, Chonchol M: FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol 2011, 22(10):1913-1922.
• [18]Seiler S, Reichart B, Roth D, Seibert E, Fliser D, Heine GH: FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment. Nephrol Dial Transplant 2010, 25(12):3983-3989.
• [19]Taylor EN, Rimm EB, Stampfer MJ, Curhan GC: Plasma fibroblast growth factor 23, parathyroid hormone, phosphorus, and risk of coronary heart disease. Am Heart J 2011, 161(5):956-962.
• [20]Ix JH, Katz R, Kestenbaum BR, de Boer IH, Chonchol M, Mukamal KJ, Rifkin D, Siscovick DS, Sarnak MJ, Shlipak MG: Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (cardiovascular health study). J Am Coll Cardiol 2012, 60(3):200-207.
• [21]Arnlov J, Carlsson AC, Sundstrom J, Ingelsson E, Larsson A, Lind L, Larsson TE: Higher fibroblast growth factor-23 increases the risk of all-cause and cardiovascular mortality in the community. Kidney Int 2012.
• [22]Johansson H, Oden A, Kanis J, McCloskey E, Lorentzon M, Ljunggren O, Karlsson MK, Thorsby PM, Tivesten A, Barrett-Connor E, et al.: Low serum vitamin D is associated with increased mortality in elderly men: MrOS sweden. Osteoporos Int 2012, 23(3):991-999.