FGF23 (Fibroblast Growth Factor-23) and Incident Hypertension in Young and Middle-Aged Adults

Abstract

Blacks have the highest prevalence of hypertension in the United States. Higher levels of FGF23 (fibroblast growth factor-23) have been associated with worse cardiovascular outcomes. Whether FGF23 is associated with rising blood pressure (BP) and racial differences in incident hypertension is unclear. We studied 1758 adults (45.0±3.7 years; 57.8% female; 36.9% black) without hypertension or cardiovascular disease who participated in the year 20 (2005-2006) follow-up examination of the CARDIA study (Coronary Artery Risk Development in Young Adults). We investigated the associations of baseline (year 20) cFGF23 (C-terminal FGF23) levels with longitudinal BP patterns and incident hypertension (defined as being on antihypertensive medication, systolic BP ≥130 or diastolic BP ≥80 mm Hg) during 2 follow-up visits (years 25 and 30). During follow-up, 35.2% of participants developed hypertension. In multivariable linear mixed models, there were greater increases in systolic BP from year 20 to 25 and year 25 to 30 in the highest FGF23 quartile relative to the lowest quartile (+2.1 mm Hg, =0.0057 and +2.2 mm Hg,=0.0108, respectively for each time period), whereas there were greater increases in diastolic BP from year 20 to 25 in the highest quartile relative to the lowest (+1.6 mm Hg; =0.0024). In multivariable modified Poisson regression analyses, the highest FGF23 quartile was associated with a 45% greater risk of developing hypertension during follow-up compared with the lowest quartile (relative risk, 1.45 [1.18-1.77]). Results did not vary by race (=0.1523). Higher FGF23 levels are independently associated with rising BP over time and an increased risk of incident hypertension but not racial differences in hypertension.

Rostral ventrolateral medulla neuron activity is suppressed by Klotho and stimulated by FGF23 in newborn Wistar rats

“…Accordingly, FGF23 levels are increased in the frontal lobe of CKD patients (Marebwa et al, 2018), where FGF23 is shown to act directly on hippocampal neurons of CKD patients (Haffner and Leifheit-Nestler, 2017). A previous study showed that higher serum levels of FGF23 were independently associated with increased BP (Akhabue et al, 2018). Based on the aforementioned studies, we believe that the increased levels of FGF23 in the CSF of patients with CKD could stimulate RVLM and thus sympathetic nerve activity leading to hypertension in those patients.…”

“…Klotho is also known to be a component of the FGF23 receptor (FGFR1) (Erben, 2017). FGF23 (251 amino acids; molecular weight, 32 kDa), mainly produced by osteocytes and osteoblasts, is related to the elimination of serum phosphate in the kidneys (Bech et al, 2015) and is reported to cause myocardial hypertrophy, atherosclerosis, and hypertension (Akhabue et al, 2018). Moreover, a previous study shows that the high serum FGF23 levels cause hypertension in patients with CKD (Li et al, 2018).…”

Fibroblast growth factor 23 and tubular sodium handling in young patients with incipient chronic kidney disease

“…Whether the associations of FGF23 levels with LVH in patients of all ages with [ 6–8 ] or without known CKD [ 46 , 47 ] are mediated through predominantly direct effects of FGF23 on the myocardium independent of hypertension [ 9 ] and renal impairment [ 12 ], or indirectly through BP changes, remains debatable. Most studies reported weak or no independent associations between FGF23 and BP [ 11 ] although recently higher FGF23 levels were independently associated with incident hypertension in younger adults without CKD [ 48 ]. We did not elicit significant associations between FGF23 levels and either systolic or diastolic BP measurements.…”

Approach and Management of Hypertension After Kidney Transplantation

“…The relationship of FGF 23 levels in the pre-and post-kidney transplant period to BP level or development of HTN after kidney transplantation is unknown. However, given that a higher level of FGF23 is associated with increased SBP and DBP as well as an incident HTN in 1,758 non-hypertensive young adults without CKD or CVD (114), this association may hold true for the transplant population. Despite this, further studies are necessary.…”