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

Panwar, Bhupesh; Judd, Suzanne E.; Wadley, Virginia G.; Jenny, Nancy S.; Howard, Virginia J.; Safford, Monika M.; Gutiérrez, Orlando M.

doi:10.1001/jamacardio.2018.0139

Cited by 28 publications

(17 citation statements)

References 41 publications

(102 reference statements)

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“…These data have suggested an independent association between high FGF23 levels and the risk for increased cardiovascular morbidity events (such as hospitalization for HF) and mortality in all the investigated patient groups . Notably, the link between FGF23 and HF‐associated endpoints was reported to be especially strong, while the association to atherosclerosis‐related cardiovascular endpoints was modest . In HF patients the association between FGF23 levels and outcome was modified by variable Klotho levels and high FGF23 plus low Klotho levels showed specifically strong impact upon renin–angiotensin–aldosterone system inhibitor efficacy in terms of endpoint reduction .…”

Section: Introductionmentioning

confidence: 84%

Limited role for fibroblast growth factor 23 in assessing prognosis in heart failure patients: data from the TIME‐CHF trial

Stöhr

Brandenburg

Heine

et al. 2020

European J of Heart Fail

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Aim Fibroblast growth factor 23 (FGF23) is an intensively studied biomarker at the crossroads of cardiovascular disease, heart failure (HF) and chronic kidney disease. Independent associations between increasing FGF23 levels and cardiovascular events were found in many, but not all studies. By analysing data from the TIME‐CHF cohort, we sought to investigate the prognostic value of FGF23 in an elderly, multimorbid HF patient cohort. We determined differences between intact (iFGF23) and C‐terminal FGF23 (cFGF23) regarding their prognostic value and their levels over time in different HF subgroups according to left ventricular ejection fraction (LVEF). Methods and results In this multicentre trial of 622 patients with symptomatic HF aged ≥60 years, we determined iFGF23 and cFGF23 at baseline, 3, 6 and 12‐month follow‐up. In unadjusted analyses, cFGF23 significantly predicted all HF‐related outcomes at all time points. The predictive value of iFGF23 was less and not statistically significant at baseline. After multivariable adjustments, the association between both cFGF23 and iFGF23 and outcome lost statistical significance apart from cFGF23 at month 3. Overall, patients with preserved and mid‐range LVEF had higher levels of iFGF23 and cFGF23 than those with reduced LVEF. Levels decreased significantly during the first 3 months in mid‐range and reduced LVEF patients, but did not significantly change over time in those with preserved LVEF. Conclusions Fibroblast growth factor 23 is of limited value regarding risk prediction in this elderly HF population. Potentially heterogeneous roles of FGF23 in different LVEF groups deserve further investigation.

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Section: Introductionmentioning

confidence: 84%

Limited role for fibroblast growth factor 23 in assessing prognosis in heart failure patients: data from the TIME‐CHF trial

Stöhr

Brandenburg

Heine

et al. 2020

European J of Heart Fail

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“…GDF15 regulates inflammation and apoptosis, both key mechanisms in cardiac remodelling that are potentially associated with incident HF 48,49 . FGF23 is released by the osteocytes and is essential for the regulation of the metabolism of phosphate, calcium and vitamin D. Importantly, FGF23 promotes myocardial fibrosis and has been associated with coronary heart disease and HF 50,51 .…”

Section: Extracellular Matrix Remodelling Angiogenesis and Growth CLmentioning

confidence: 99%

Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure

Ferreira

Verdonschot

Collier

et al. 2019

Circ: Heart Failure

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Background: Identifying the mechanistic pathways potentially associated with incident HF may provide a basis for novel preventive strategies. Methods and Results:To identify proteomic biomarkers and the potential underlying mechanistic pathways that may be associated with incident HF defined as first hospitalization for HF, a nestedmatched case-control design was used with cases (incident HF) and controls (without HF) selected from 3 cohorts (>20,000 individuals). Controls were matched on cohort, follow-up time, age, and sex.Two independent sample sets (a "discovery" set, with 286 cases and 591 controls and a "replication" set with 276 cases and 280 controls) were used to discover and replicate the findings. 252 circulating proteins in the plasma were studied. Adjusting for the matching variables age, sex, and follow-up time (and correcting for multiplicity of tests), 89 proteins were found to be associated with incident HF in the discovery phase, of which 38 were also associated with incident HF in the replication phase.These 38 proteins pointed to 4 main network clusters underlying incident HF: 1) inflammation and apoptosis, indicated by the expression of the TNF-family members; 2) extracellular matrix remodelling, angiogenesis and growth, indicated by the expression of proteins associated with collagen metabolism, endothelial function and vascular homeostasis; 3) blood pressure regulation, indicated by the expression of natriuretic peptides and proteins related to the renin angiotensin aldosterone system; and 4) metabolism, associated with cholesterol and atherosclerosis.Conclusion: Clusters of biomarkers associated with mechanistic pathways leading to HF were identified linking inflammation, apoptosis, vascular function, matrix remodelling, blood pressure control and metabolism. These findings provide important insight on the pathophysiological mechanisms leading to HF.

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“…This indicates that the negative CV impact of FGF23 is likely to develop since early stage CKD where FGF23 starts to increase. FGF23 also shows an independent association with accelerated CKD progression in early (stages 3 and lower) CKD patients [ 82 ] as well as with increased risk of coronary heart disease in the general population [ 83 ].…”

Section: Cardiac Effects Of Middle Moleculesmentioning

confidence: 99%

Cardiotoxicity of Uremic Toxins: A Driver of Cardiorenal Syndrome

Lekawanvijit

2018

Toxins

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Cardiovascular disease (CVD) is highly prevalent in the setting of chronic kidney disease (CKD). Such coexistence of CVD and CKD—the so-called “cardiorenal or renocardiac syndrome”—contributes to exponentially increased risk of cardiovascular (CV) mortality. Uremic cardiomyopathy is a characteristic cardiac pathology commonly found in CKD. CKD patients are also predisposed to heart rhythm disorders especially atrial fibrillation. Traditional CV risk factors as well as known CKD-associated CV risk factors such as anemia are insufficient to explain CV complications in the CKD population. Accumulation of uremic retention solutes is a hallmark of impaired renal excretory function. Many of them have been considered inert solutes until their biological toxicity is unraveled and they become accepted as “uremic toxins”. Direct cardiotoxicity of uremic toxins has been increasingly demonstrated in recent years. This review offers a mechanistic insight into the pathological cardiac remodeling and dysfunction contributed by uremic toxins with a main focus on fibroblastic growth factor-23, an emerging toxin playing a central role in the chronic kidney disease–mineral bone disorder, and the two most investigated non-dialyzable protein-bound uremic toxins, indoxyl sulfate and p-cresyl sulfate. Potential therapeutic strategies that could address these toxins and their relevant mediated pathways since pre-dialysis stages are also discussed.

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

Abstract: Higher FGF23 concentrations were associated with greater risk of CHD. Heterogeneity in the association by sex may be caused by differences in the distribution of plasma FGF23 concentrations or the use of hormone therapy in men vs women.

Cited by 28 publications

References 41 publications

Limited role for fibroblast growth factor 23 in assessing prognosis in heart failure patients: data from the TIME‐CHF trial

Limited role for fibroblast growth factor 23 in assessing prognosis in heart failure patients: data from the TIME‐CHF trial

Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure

Cardiotoxicity of Uremic Toxins: A Driver of Cardiorenal Syndrome

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