Serum fibroblast growth factor-23 and incident hypertension

Fyfe‐Johnson, Amber L.; Alonso, Álvaro; Selvin, Elizabeth; Bower, Julie K.; Pankow, James S.; Agarwal, Sunil; Lutsey, Pamela L.

doi:10.1097/hjh.0000000000000936

Cited by 40 publications

(24 citation statements)

References 47 publications

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“…Specific associations have been reported for incident hypertension, LVH, incident HF, higher coronary calcium scores, and incident coronary heart disease 17, 19, 27, 28. In this study we confirmed previous findings reported by Kestenbaum et al linking serum FGF‐23 to incident HF, and further studied the association with subtypes of HFpEF and HFrEF.…”

Section: Discussionsupporting

confidence: 92%

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Almahmoud

Soliman

Bertoni

et al. 2018

JAHA

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BackgroundHigher fibroblast growth factor‐23 (FGF‐23) levels are associated with incident heart failure (HF) in MESA (the Multiethnic Study of Atherosclerosis). FGF‐23 is also associated with left ventricular hypertrophy. Whether the FGF‐23 association with HF is similar for heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) is not well established.Methods and ResultsWe studied 6542 participants (mean age 62±10 years, 53% women, mean estimated glomerular filtration rate of 81±18 mL/min per 73 m2) from MESA who were free of cardiovascular disease at baseline (2000–2002). HF events were ascertained by an adjudication committee for a median follow‐up of 12.1 years. We classified HF events as HFrEF (ejection fraction [EF] <50%) or HFpEF [EF] ≥50%) at the time of diagnosis. Cox proportional hazard regression was used to compute hazard ratios and 95% confidence intervals for the association between baseline serum FGF‐23 and incident HFrEF and HFpEF. A total of 134 events were classified as HFpEF, 151 HFrEF, and 49 unknown EF. Following imputation, 149 were classified as HFpEF, 176 HFrEF, and 291 participants had HF (34 participants had HFpEF then HFrEF). In the fully adjusted model, higher FGF‐23 levels were associated with incident HFpEF but not with HFrEF (hazard ratio 1.29, 95% confidence interval, 1.08–1.54) versus (hazard ratio 1.04, 95% confidence interval, 0.84–1.29) for each 20 pg/mL higher serum FGF‐23 concentration.Conclusions FGF‐23 association with HF is driven by the association with HFpEF but not with HFrEF in a population‐based cohort. Further studies are needed to determine the pathological mechanisms mediating this association.

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Section: Discussionsupporting

confidence: 92%

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Almahmoud

Soliman

Bertoni

et al. 2018

JAHA

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“…10 A previous study examining a possible association of FGF23 with incident hypertension in a primarily white population of older adults suggested that individuals in the highest FGF23 decile of values had a modestly increased risk of developing hypertension. 25 Our study extends prior analyses in two significant ways. By the time US adults reach ages 55–64, the prevalence of hypertension already exceeds 50%.…”

Section: Discussionsupporting

confidence: 60%

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

et al. 2018

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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.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…Whether these cardiac effects of FGF23 are the result of direct actions targeting the myocardial cells, or indirectly by stimulation of traditional cardiovascular risk factors like hypertension or activation of the renin–angiotensin–aldosterone system (RAAS) remains ill-defined and the subject of ongoing research [ 10 ]. Clinically, the association of hypertension with elevated levels of FGF23 has not been consistent, showing mostly a rather weak association in the absence of overt renal dysfunction [ 11 ], and hypertension may be absent in experimental models where FGF23 levels are elevated [ 12 ]. Of particular interest are the recent experimental data suggesting direct effects of FGF23 on the Na + Cl − co-transporter (NCC) of the renal distal tubular epithelium resulting in Na retention, blood volume expansion, hypertension and cardiac hypertrophy, advancing a novel explanation for the association between higher FGF23 and cardiovascular morbidity and mortality [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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

Freundlich

Cuervo

Abitbol

2019

Clinical Kidney Journal

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BackgroundExperimental studies have shown fibroblast growth factor 23 (FGF23)-mediated upregulation of the distal tubule sodium/chloride (Na+Cl−) co-transporter leading to increased Na reabsorption, volume expansion and hypertension. However, data on the associations of FGF23 with renal Na regulation and blood pressure (BP) are lacking in young CKD patients.MethodsFGF23 and other determinants of mineral metabolism, plasma renin activity (PRA), fractional excretion of Na (FENa) and BP, were analyzed at a single center in 60 patients aged 5–22 years with CKD Stages 1 (n = 33) and Stages 2–3 (n = 27) defined by cystatin C- and creatinine-based estimating equations (estimated glomerular filtration rate, eGFR). Associations between FGF23 and renal Na handling were explored by regression analysis.ResultsMedian FGF23 levels were higher in CKD Stages 2–3 versus CKD 1 (119 versus 79 RU/mL; P < 0.05), with hyperparathyroidism [parathyroid hormone (PTH) >69 pg/mL] in only few subjects with CKD Stages 2–3. Median FENa was comparable in both subgroups, but with proportionally more values above the reference mean (0.55%) in CKD Stages 2–3 and 3-fold higher (1.6%) in CKD Stage 3. PRA was higher in CKD Stages 2–3 (P < 0.05). Meanwhile in CKD Stage 1, FGF23 did not associate with FENa, and in CKD Stages 2–3 FGF23 associated positively with FENa (r = 0.4; P < 0.05) and PTH (r = 0.45; P < 0.05), and FENa associated with FE of phosphate (r = 0.6; P < 0.005). Neither FGF23 nor FENa was associated with systolic or diastolic BP in either subgroup. The negative association of eGFR by cystatin with FENa remained the strongest predictor of FENa by multivariable linear regression in CKD Stages 2–3.ConclusionsThe elevated FGF23, FENa and PRA and the positive association of FGF23 with FENa do not suggest FGF23-mediated increased tubular Na reabsorption and volume expansion as causing hypertension in young patients with incipient CKD.

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Serum fibroblast growth factor-23 and incident hypertension

Cited by 40 publications

References 47 publications

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

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

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

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