Plasma Fibroblast Growth Factor 23, Parathyroid Hormone, 25-Hydroxyvitamin D3, and Risk of Heart Failure: A Prospective, Case-Cohort Study

Giuseppe, Romina di; Buijsse, Brian; Hirche, Frank; Wirth, Janine; Arregui, María; Westphal, Sabine; Isermann, Berend; Hense, Hans Werner; Dierkes, Jutta; Boeing, Heiner; Stangl, Gabriele I.; Weikert, Cornelia

doi:10.1210/jc.2013-2963

Cited by 50 publications

(44 citation statements)

References 37 publications

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“…41 The Physicians' Health Study (mean age, 58.6 years) and the European Prospective Investigation into Cancer and Nutrition-Potsdam study also showed no association between plasma vitamin D-binding protein or 25(OH)D3 with risk of HF. 22,26 The finding that 25OHD deficiency is not associated with HF in older adults is consistent with the findings from several cross-sectional population studies that 25OHD is not associated with any biochemical conduction or echocardiographic outcomes. 16,17 …”

Section: Vitamin D and Incident Hfsupporting

confidence: 88%

“…Two studies have shown elevated PTH to be associated with HF independent of known risk factors, including hypertension and renal dysfunction, 20,21 whereas 1 study suggested the association to be present in obese subjects only. 22 We have shown elevated PTH (>55.6 pg/mL) to be associated with increased HF risk in both men with and without established CVD (MI/stroke). Although the association appeared to be stronger in obese men, there was no evidence of an interaction.…”

Section: Pth and Incident Hfmentioning

confidence: 84%

“…Two prospective studies in older adults have shown PTH levels to be related to incident HF 20,21 independent of known risk factors for HF, whereas 1 study conducted in middle-aged population showed the association to be present in obese subjects only. 22 Moreover, whether PTH is associated with incident HF in older adults with established CVD, who are at high risk of HF, has not been studied. In contrast, the prospective association between vitamin D and HF has been studied in several population studies, but the results have been equivocal, with some prospective studies showing an association between low vitamin D status and HF, [23][24][25] others have shown null results.…”

mentioning

confidence: 99%

“…In contrast, the prospective association between vitamin D and HF has been studied in several population studies, but the results have been equivocal, with some prospective studies showing an association between low vitamin D status and HF, [23][24][25] others have shown null results. 20,22,26 We, therefore, examined the relationships between PTH and 25-hydroxyvitamin D (25OHD, a marker of circulating active vitamin D levels), as well as markers of mineral metabolism (calcium and phosphate) and incident HF in older men with and without established CVD (myocardial infarction [MI] or stroke).…”

mentioning

confidence: 99%

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Elevated Parathyroid Hormone, But Not Vitamin D Deficiency, Is Associated With Increased Risk of Heart Failure in Older Men With and Without Cardiovascular Disease

Wannamethee

Welsh

Papacosta

et al. 2014

Circ: Heart Failure

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Background-Hyperparathyroidism and low vitamin D status have been implicated in the pathogenesis of heart failure (HF).We examined the prospective associations between parathyroid hormone (PTH), circulating 25-hydroxyvitamin D, and markers of mineral metabolism and risk of incident HF in older men with and without established cardiovascular disease. Methods and Results-Prospective study of 3731 men aged 60 to 79 years with no prevalent HF followed up for a mean period of 13 years, in whom there were 287 incident HF cases. Elevated PTH (≥55.6 pg/mL; top quarter) was associated with significantly higher risk of incident HF after adjustment for lifestyle characteristics, diabetes mellitus, blood lipids, blood pressure, lung function, heart rate, renal dysfunction, atrial fibrillation, forced expiratory volume in 1 second, and C-reactive protein (hazards ratio, 1.66; 95% confidence interval, 1.30-2.13). The increased risk was seen in both men with and without previous myocardial infarction or stroke (hazards ratio, 1.72; 95% confidence interval, 1.07-2.76; hazards ratio, 1.70; 95% confidence interval, 1.25-2.30, respectively). Elevated PTH was significantly associated with N-terminal probrain natriuretic peptide, a marker of left ventricular wall stress. By contrast, 25-hydroxyvitamin D and other markers of mineral metabolism including serum calcium and phosphate showed no significant association with incident HF after adjustment for age. Conclusions-Elevated PTH, but not 25-hydroxyvitamin D or other markers of mineral metabolism, is associated with increased risk of HF in both older men with and without myocardial infarction/stroke. This increased risk was not explained by its association with known risk factors for HF. Further studies are now needed to elucidate the mechanisms underlying this association. (Circ Heart Fail. 2014;7:732-739.)

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Section: Vitamin D and Incident Hfsupporting

confidence: 88%

Section: Pth and Incident Hfmentioning

confidence: 84%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Elevated Parathyroid Hormone, But Not Vitamin D Deficiency, Is Associated With Increased Risk of Heart Failure in Older Men With and Without Cardiovascular Disease

Wannamethee

Welsh

Papacosta

et al. 2014

Circ: Heart Failure

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“…43 Single nucleotide polymorphisms (SNPs) in FGF-23 have been identified as potential risk factors for cardiac abnormalities in Kawasaki disease, 44 and the serum levels of FGF-23 have been recognized as biomarkers for cardiovascular failure. 45 FGF-23 had also been linked to greater risks of left ventricular hypertrophy in patients with CKD. 46 However, no conclusion has been reached whether this effect is via α-klotho independent pathways or indirectly due to the renal effects of FGF-23.…”

Section: Heartmentioning

confidence: 99%

Recent Advances in Fibro-blast Growth Factor-23 Functions

Nayani

Xiao

2016

Nephrol Open J

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During the past decade a lot of work has been done to better understand the roles of fibroblast growth factor-23 (FGF-23); a relatively newly discovered endocrine hormone, in multiple organ systems in the body. This review focuses on expressions of FGF-23, coexpressions of α-Klotho and FGF receptors, and FGF-23 mediated end-organ effects in the physiological and pathological conditions. We also discuss the controversial reports regarding α-Klotho-dependent and α-Klotho-independent functions of FGF-23. EXPRESSION OF FGF-23, α-KLOTHO, AND FGF RECEPTORS FGF-23FGF-23 is a family member of 22 fibroblast growth factors (FGFs) including FGF-1-FGF-23, all of which are not only structurally but also evolutionarily related proteins. These FGFs have been classified as being paracrine (15 FGFs), endocrine (3 FGFs), or intracrine (4 FGFs) 1 and using a mammalian (murine) model the endocrine FGFs, especially FGF-23 an approximately 32 kD protein, 2 have been thoroughly investigated in recent years.FGF-23 is expressed in multiple cells in the body. It has been conclusively shown to be secreted in bone by cells of the osteoblast lineage and osteocytes, as a part of the lacunacanalicular system, under the influence of phosphate.3 Local factors derived from bone itself also regulate its expression as seen in cases of inactivating mutations of PHEX which results in increased transcription and circulating levels of It is also expressed in the pericytelike endothelial cells surrounding the venous sinusoids in bone marrow 5 and in the thymus.2 FGF-23 also plays a part in the body's immune response since its expression is induced in activated dendritic cells and macrophages in response to inoculation with E. coli and S. aureus via nuclear factor-kappa B (NF-κB) signaling. 6 FGF-23 is found to be expressed in the venterolateral (VL) thalamic nucleus as well. In addition, FGF-23 is also expressed in heart by cardiac interstitial fibroblasts. 7,8 Apart from these tissues, there is also FGF-23 expression seen in the muscle, spleen, skin, lung, testes, kidney, and liver to a much lesser extent. α-Klotho α-Klotho is a unique molecule that establishes a regulatory system of calcium homeostasis by affecting transepithelial transport of calcium, parathyroid hormone secretion, and FGF-23 signal transduction.9 Evolutionarily the FGF-23-α-Klotho system is part of a major milestone in vertebrate evolution that started in the ocean when the early piscine ancestors acquired the bony endoskeleton.10 α-Klotho has been demonstrated to enhance FGF-23 activity over 10-fold 11 and has also been identified as a necessary co-receptor for FGF-23 binding due to the phenotypic similarity observed in α-Klotho and FGF-23 knockout mice, i.e.; hyperphosphatemia and hypercalcemia. 11 α-Klotho is expressed in high levels in kidney, parathyroidgland (PTG), testis, ovary, brain, pituitary, and apical plasma membrane of ependymal cells in the choroid plexus but

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Association of Fibroblast Growth Factor 23 With Risk of Incident Coronary Heart Disease in Community-Living Adults

et al. 2018

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Plasma Fibroblast Growth Factor 23, Parathyroid Hormone, 25-Hydroxyvitamin D3, and Risk of Heart Failure: A Prospective, Case-Cohort Study

Abstract: Our findings provide epidemiological evidence for a positive relationship between FGF23 and risk of HF. The role of PTH in the development of HF remains unclear, in particular in obese individuals, until further confirmation in other studies. 25(OH)D3 was not related to HF.

Cited by 50 publications

References 37 publications

Elevated Parathyroid Hormone, But Not Vitamin D Deficiency, Is Associated With Increased Risk of Heart Failure in Older Men With and Without Cardiovascular Disease

Elevated Parathyroid Hormone, But Not Vitamin D Deficiency, Is Associated With Increased Risk of Heart Failure in Older Men With and Without Cardiovascular Disease

Recent Advances in Fibro-blast Growth Factor-23 Functions

Association of Fibroblast Growth Factor 23 With Risk of Incident Coronary Heart Disease in Community-Living Adults

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