Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals.
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.


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).


CONCLUSIONS
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.
Mirza
Majd A I
MA
Department of Medical Sciences, Uppsala University, Uppsala Sweden. majd.mirza@medsci.uu.se
Alsiö
Johan
J
Hammarstedt
Ann
A
Erben
Reinhold G
RG
Michaëlsson
Karl
K
Tivesten
Asa
A
Marsell
Richard
R
Orwoll
Eric
E
Karlsson
Magnus K
MK
Ljunggren
Osten
O
Mellström
Dan
D
Lind
Lars
L
Ohlsson
Claes
C
Larsson
Tobias E
TE
D015502:Absorptiometry, Photon; D052242:Adiponectin / Q000097:blood; D050154:Adiposity; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D016014:Linear Models; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden; D015854:Up-Regulation; D055105:Waist Circumference; D049629:Waist-Hip Ratio
C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; C000717427:FGF23 protein, human; D007328:Insulin; D020738:Leptin; D008055:Lipids; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23