Fibroblast Growth Factor 23 Is Associated With Carotid Plaque Presence and Area: The Northern Manhattan Study
Nirav H Shah1, Chuanhui Dong1, Mitchell S V Elkind1
1From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY.
Insights
Higher levels of fibroblast growth factor 23 (FGF23) are linked to increased carotid plaque presence and area, suggesting a role in atherosclerosis. This finding is independent of chronic kidney disease (CKD).
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Nephrology
Background:
- Fibroblast growth factor 23 (FGF23) is a hormone regulating phosphate and is linked to adverse outcomes.
- The role of FGF23 in atherosclerosis, particularly in diverse populations, remains unclear.
- Population-based studies investigating FGF23 and atherosclerosis are lacking.
Purpose of the Study:
- To investigate the association between elevated FGF23 levels and carotid atherosclerosis.
- To examine the relationship between FGF23 and carotid plaque presence, area, and echogenicity.
- To explore FGF23's role in atherosclerosis within the race/ethnically diverse Northern Manhattan Study (NOMAS) cohort.
Main Methods:
- Utilized data from 1512 stroke-free participants in the NOMAS study with FGF23 and carotid ultrasound data.
- Employed multivariable linear and logistic regression to assess FGF23's correlation with carotid plaque characteristics.
- Adjusted analyses for sociodemographic factors, vascular risk factors, and estimated glomerular filtration rate (eGFR).
Main Results:
- Participants in the highest FGF23 quintile showed increased likelihood of carotid plaque (OR, 1.49) and larger plaque area (β=0.32 mm²).
- Log-transformed FGF23 (LnFGF23) correlated with greater odds of plaque presence (OR, 1.26 per LnFGF23) and plaque area (β=0.19 mm² per LnFGF23).
- These associations remained significant after adjusting for eGFR, demographics, and vascular risk factors.
Conclusions:
- Elevated FGF23 levels are associated with a higher likelihood and burden of carotid atherosclerosis.
- The link between higher FGF23 and carotid atherosclerosis is independent of chronic kidney disease (CKD).
- Atherosclerosis may be a key mechanism mediating FGF23's association with cardiovascular events and stroke.
Objective:
Elevated fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate homeostasis, has been associated with mortality, cardiovascular events, and stroke, and to arterial calcification in chronic kidney disease, but its role in atherosclerosis is unclear and population-based studies are lacking. We hypothesized that elevated FGF23 would associate with carotid plaque presence, area, and echogenicity in the race/ethnically diverse community-based Northern Manhattan Study (NOMAS) sample.
Approach And Results:
There were 1512 stroke-free NOMAS participants with FGF23 and 2-dimensional carotid ultrasound data (mean age, 68±9 years; 61% women; 62% Hispanic, 18% black, and 18% white). We used multivariable linear and logistic regression to evaluate FGF23, continuously and by quintiles, as a correlate of carotid plaque, plaque area (cubic root transformed), and echogenicity adjusting for sociodemographic and vascular risk factors. Participants with FGF23 levels in the top quintile were more likely to have carotid plaque (odds ratio, 1.49; 95% confidence interval, 1.02-2.19; P=0.04) and larger plaque area (β=0.32 mm(2), 95% confidence interval, 0.10-0.53 mm(2); P=0.004) than those in the lowest quintile, adjusting for estimated glomerular filtration rate, demographics, and vascular risk factors. Linear regression models also showed that log transformed FGF23 (LnFGF23) associated with greater odds of plaque presence (odds ratio, 1.26 per LnFGF23; 95% confidence interval, 1.01-1.58; P=0.04), and plaque area (β=0.19 mm(2) per LnFGF23; 95% confidence interval, 0.07-0.31 mm(2); P=0.002).
Conclusions:
Higher FGF23 associated with greater likelihood and burden of carotid atherosclerosis independent of CKD. Atherosclerosis may be a mechanism through which FGF23 increases cardiovascular events and stroke.
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