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Elevated FGF23 increases all-cause mortality risk
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The risks for vascular and nonvascular mortality are independently related to elevated fibroblast growth factor 23, according to recent findings.
Myles Wolf, MD, MMSc , director of the Institute for Public Health and Medicine Center for Translational Metabolism and Health at Northwestern University, and colleagues evaluated data from the Northern Manhattan Study on 2,525 adults (mean age, 68.9 years; 53.6% Hispanic; 23.4% non-Hispanic black) with available blood samples for baseline fibroblast growth factor 23 (FGF23). Participants were enrolled in the study between 1993 and 2001. Researchers sought to determine the relationship between elevated FGF23 and the risk for all-cause specific mortality. Follow-up was a median of 14 years.
During follow-up, there were 1,198 deaths; causes were vascular in 474 participants, nonvascular in 612 and unknown in 112. Sudden death was the leading vascular cause of death (n = 226), followed by stroke (n = 60), myocardial infarction (n = 56), heart failure (n = 47) and other (n = 85). Cancer was the leading nonvascular cause of death (n = 233), followed by chronic obstructive pulmonary disease (n = 116), infection (n = 111) and other (n = 152).
Risk for all-cause mortality was independently associated with higher FGF23, expressed on a continuous scale (HR = 2.71 per 1-unit increase in natural log transformed FGF23; 95% CI, 1.3-5.65). The risk for death due to infection also was linked to higher FGF23 (HR = 1.55 per 1-unit increase in natural log transformed FGF23; 95% CI, 1.16-2.07) when analyzed on a continuous scale.
Impaired kidney function, prevalent cardiovascular disease and baseline 25-hydroxyvitamin D levels did not modify the relationship between FGF23 and all-cause mortality.
The relationship between FGF23 and risk for all-cause mortality was not modified by black race, but there was an interaction between FGF23 and Hispanic ethnicity (P = .002 for interaction). Compared with Hispanic participants, the overall crude death rate was higher among non-Hispanic participants. Compared with non-Hispanic participants, Hispanic participants with elevated FGF23 had an increased risk for nonvascular mortality (P = .03 for interaction) and cancer death (P = .01 for interaction).
“Elevated FGF23 was independently associated with increased risk of all-cause mortality and death due to both vascular and nonvascular causes in a racially and ethnically diverse general population regardless of presence of absence of a history of CVD or kidney disease at baseline,” the researchers wrote. “Elevated FGF23 was also associated with increased risk of cancer death specifically among Hispanic Americans, a rapidly growing segment of the U.S. population in which there has been limited data on FGF23 and clinical outcomes.” – by Amber Cox
Disclosure: Wolf reports serving as a consultant for or receiving honoraria from Amgen, Diasorin, Keryx, Pfizer, Sanofi and Ultragenyx. Please see the full study for a list of all other authors’ relevant financial disclosures.
Perspective
Back to TopHolly Kramer
The study by Souma and colleagues used data from the Northern Manhattan Study, a diverse cohort, to examine the association between fibroblast growth factor (FGF) 23 levels and mortality. The investigators grouped the FGF23 levels into quintiles with FGF23 levels ranging from as low as 36 RU/ml in the lowest quintile to 131 RU/ml in the highest quintile. Individuals in the highest quintile had an approximately two-fold increased risk for mortality during a median follow-up of 14 years compared with the lowest quintile. However, significant trends in vascular, nonvascular and even cancer mortality were noted across quintiles of FGF23 levels even after accounting for differences in comorbid conditions across the FGF23 quintiles. FGF23 has previously been linked with cardiovascular disease, stroke and even atrial fibrillation. This study adds new information because it shows that high FGF23 levels may reflect a heightened risk for nonvascular related death including cancer death. FGF23 is a phosphatonin that turns on transporters in the kidney to increase urinary excretion of phosphate. We know that high phosphate intake over a prolonged period elevates production of FGF23 levels. Processed foods which are ubiquitous in the U.S. diet are frequently preserved with inorganic phosphates. Emerging studies also reveal that diets high in animal protein and low in fiber and magnesium may lead to high FGF23 levels. Diet is strongly associated with the development of numerous chronic diseases including cancer and high FGF23 levels may reflect certain dietary practices. Future studies should explore methods to reduce FGF23 levels, perhaps with dietary interventions.
Disclosure: Kramer reports no relevant financial disclosures.
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