Fibroblast Growth Factor 23 and Cause-Specific Mortality in the General Population: The Northern Manhattan Study
Nao Souma1, Tamara Isakova1, David Lipiszko1
1Division of Nephrology and Hypertension, Department of Medicine, and Center for Translational Metabolism and Health, Institute for Public Health and Medicine (N.S., T.I., D.L., M.W.), Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611; Evelyn F. McKnight Brain Institute (R.L.S., C.D., C.B.W.) and Departments of Neurology (R.L.S., C.B.W.), Public Health Sciences (R.L.S., C.B.W.), Human Genomics (R.L.S.), Medicine (A.J.M.), and the Neuroscience Program (R.L.S., C.B.W.), Leonard M. Miller School of Medicine, University of Miami, Miami, Florida 33136; and Departments of Neurology (M.S.V.E., J.T.D.) and Medicine (S.J.S.), College of Physicians and Surgeons, and Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York, New York 10032.
Context:
An elevated fibroblast growth factor (FGF) 23 is an independent risk factor for cardiovascular disease and mortality in patients with kidney disease. The relationship between FGF23 and cause-specific mortality in the general population is unknown.
Objective:
To investigate the association of elevated FGF23 with the risk of cause-specific mortality in a racially and ethnically diverse urban general population.
Design, Setting, Participants:
The Northern Manhattan Study is a population-based prospective cohort study. Residents who were > 39 years old and had no history of stroke were enrolled between 1993 and 2001. Participants with available blood samples for baseline FGF23 testing were included in the current study (n = 2525).
Main Outcome Measures:
Cause-specific death events.
Results:
A total of 1198 deaths (474 vascular, 612 nonvascular, 112 unknown cause) occurred during a median follow-up of 14 years. Compared to participants in the lowest FGF23 quintile, those in the highest quintile had a 2.07-fold higher risk (95% confidence interval [CI], 1.45, 2.94) of vascular death and a 1.64-fold higher risk (95% CI, 1.22, 2.20) of nonvascular death in fully adjusted models. Higher FGF23 was independently associated with increased risk of mortality due to cancer, but only in Hispanic participants (hazard ratio per 1 unit increase in ln FGF23 of 1.87; 95% CI, 1.40, 2.50; P for interaction = .01).
Conclusions:
Elevated FGF23 was independently associated with increased risk of vascular and nonvascular mortality in a diverse general population and with increased risk of cancer death specifically in Hispanic individuals.
