Association of Fibroblast Growth Factor 23 With Recurrent Cardiovascular Events in Patients After an Acute Coronary Syndrome

Bergmark, Brian A; Udell, Jacob A.; Morrow, David A.; Cannon, Christopher P.; Steen, Dylan; Jarolím, Petr; Budaj, Andrzej; Hamm, Christian W.; Guo, Jianping; Im, KyungAh; Kuder, Julia; Braunwald, Eugene; Sabatine, Marc S.; O’Donoghue, Michelle L.

doi:10.1001/jamacardio.2018.0653

Cited by 37 publications

(45 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…When renal function declines in patients with chronic kidney disease the concentration of circulating FGF-23 is increased in response to persistent hyperphosphatemia [ 4 ]; however, increased levels of FGF-23 have also been associated with an increased risk of developing heart failure, cardiovascular disease, and cardiovascular death independent of renal function and other cardiovascular risk factors [ 5 , 6 ]. In patients with combined type 2 diabetes and CAD, FGF-23 independently predicts adverse cardiovascular outcome [ 7 ] and, additionally, elevated FGF-23 concentrations following acute coronary syndrome are associated with an increased risk of CV death and hospitalization due to heart failure [ 8 ]. Furthermore, a recent study of patients with type 2 diabetes and normal or mildly impaired kidney function showed that FGF-23 was associated with an increased risk of both major adverse cardiovascular events and all-cause mortality [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor-23 is associated with imaging markers of diabetic cardiomyopathy and anti-diabetic therapeutics

Sørensen

Bojer

Jørgensen

et al. 2020

Cardiovasc Diabetol

View full text Add to dashboard Cite

Background The biomarker fibroblast growth factor-23 (FGF-23) has been associated with increased cardiovascular morbidity and mortality in both patients with and without type 2 diabetes. The aim of this study was to evaluate the relationship between FGF-23 and cardiac structure, function and perfusion in patients with type 2 diabetes and normal or mildly impaired kidney function. Furthermore, to investigate the association between FGF-23, anti-diabetes therapy and the classic complications and risk factors associated with type 2 diabetes. Methods In this cross-sectional study, 246 patients with type 2 diabetes underwent echocardiography and advanced cardiac magnetic resonance imaging to assess left ventricular (LV) structure and function. In addition, myocardial blood flow (MBF) during rest and pharmacological stress (adenosine 140 µg/kg/min) were evaluated in 183 of the patients. Patients with eGFR < 60 ml/min/1.73 m2 were excluded. Results Median (Q1–Q3) FGF-23 was 74 (58–91) ng/L. Patients with FGF-23 above the median had lower MBF during stress (2.3 ± 0.9 vs. 2.7 ± 0.9 ml/min/g, P = 0.001) and lower overall myocardial perfusion reserve (MPR) (2.7 ± 0.8 vs. 3.3 ± 1.1, P < 0.001). LV mass (143 ± 40 vs. 138 ± 36 g, P = 0.04) and E/e* (8.5 ± 3.2 vs. 7.6 ± 2.7, P = 0.04) were higher in patients with FGF-23 above the median. In a linear model adjusted for age, sex, eGFR and hypertension, increasing FGF-23 was associated with decreased MPR (P < 0.01, R2 = 0.11) and increased E/e* (P < 0.01, R2 = 0.07). FGF-23 was lower in patients receiving glucagon like peptide-1 (GLP-1) analogues (71 (57–86) vs. 80 (60–98) ng/L, P = 0.01) than in those who did not receive GLP-1 analogues. Conclusions In patients with type 2 diabetes and normal or mildly impaired kidney function, increased levels of FGF-23 are associated with impaired cardiac diastolic function and decreased MPR, caused by a decrease in maximal MBF during stress. Use of GLP-1 analogues is associated with decreased levels of FGF-23. Clinical trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT02684331. Date of registration: February 18, 2016

show abstract

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor-23 is associated with imaging markers of diabetic cardiomyopathy and anti-diabetic therapeutics

Sørensen

Bojer

Jørgensen

et al. 2020

Cardiovasc Diabetol

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown a higher occurrence of recurrent cardiovascular events in the highest quartile of FGF-23 in patients with acute coronary syndrome as well as worse outcomes in patients with known RD, including increased frequency of heart failure and mortality 11,12,28 . A population-based study of stroke-free individuals found that FGF-23 is a risk factor for subsequent stroke independent of RD 29 , an association in CSVD with progressing vascular disease has not yet been reported.…”

Section: Discussionmentioning

confidence: 91%

Early renal dysfunction and fibroblast growth factor-23 in patients with small vessel disease-related stroke

Fandler‐Höfler

Enzinger

Kneihsl

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Interactions between cerebral small vessel disease (CSVD) and renal dysfunction (RD) have been reported, but previous studies were mostly retrospective and limited to measurements of estimated glomerular filtration rate (eGFR). In this prospective, longitudinal study of patients with CSVD-related recent small subcortical infarcts (RSSI), we aimed at a comprehensive exploration of markers of early RD and their association with microvascular brain damage. We investigated 101 stroke patients (mean age: 60.2 ± 10.7 years) with an MRI-confirmed RSSI who underwent follow-up brain MRI 15 months post-stroke. Besides serum creatinine and eGFR, we assessed urinary Albumin-Creatinine Ratio and fibroblast growth factor-23 (FGF-23). RD was classified according to recent Kidney Disease: Improving Global Outcomes criteria. We identified 24 patients with RD, only six patients revealed an eGFR <60 mL/min/1.73 m². RSSI patients with RD more often had severe white matter hyperintensities (WMH, 58% vs. 36%, p = 0.04). CSVD progression was not dependent on RD. However, patients in the highest FGF-23 quartile more frequently had new microangiopathic lesions on follow-up MRI (50% vs. 21%, p = 0.03). Early RD was found in a quarter of RSSI patients and associated with WMH severity, but not CSVD progression. High FGF-23 indicates an increased risk for ongoing microvascular brain damage, warranting further studies.

show abstract

“…With a series of eligible compounds available at present, scientists would be admired if they exerted more effort in exploring the role of Lp‐PLA2 in diseases other than atherosclerosis, particularly, in microvascular diseases that may be more sensitive to Lp‐PLA2 inhibition. In addition, the large pool of data generated from clinical trials provides numerous opportunities for comprehensive data mining, which may be beneficial to understanding the biological consequences of Lp‐PLA2 inhibition and help us to learn a profound and valuable lesson from the failure of darapladib . To conclude, we anticipate that the story of Lp‐PLA2 will continue.…”

Section: Discussion and Prospectsmentioning

confidence: 99%

“…In addition, the large pool of data generated from clinical trials provides numerous opportunities for comprehensive data mining, which may be beneficial to understanding the biological consequences of Lp-PLA2 inhibition and help us to learn a profound and valuable lesson from the failure of darapladib. [279][280][281][282][283][284][285][286][287][288] To conclude, we anticipate that the story of Lp-PLA2 will continue.…”

mentioning

confidence: 98%

Lipoprotein‐associated phospholipase A2: The story continues

Huang

Wang

Shen

2019

Medicinal Research Reviews

123

140

View full text Add to dashboard Cite

Inflammation is thought to play an important role in the pathogenesis of vascular diseases. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation‐related diseases, mainly atherosclerosis. Although darapladib, the most advanced Lp‐PLA2 inhibitor, failed to meet the primary endpoints of two large phase III trials in atherosclerosis patients cotreated with standard medical care, the research on Lp‐PLA2 has not been terminated. Novel pathogenic, epidemiologic, genetic, and crystallographic studies regarding Lp‐PLA2 have been reported recently, while novel inhibitors were identified through a fragment‐based lead discovery strategy. More strikingly, recent clinical and preclinical studies revealed that Lp‐PLA2 inhibition showed promising therapeutic effects in diabetic macular edema and Alzheimer's disease. In this review, we not only summarized the knowledge of Lp‐PLA2 established in the past decades but also emphasized new findings in recent years. We hope this review could be valuable for helping researchers acquire a much deeper insight into the nature of Lp‐PLA2, identify more potent and selective Lp‐PLA2 inhibitors, and discover the potential indications of Lp‐PLA2 inhibitors.

show abstract

Association of Fibroblast Growth Factor 23 With Recurrent Cardiovascular Events in Patients After an Acute Coronary Syndrome

Cited by 37 publications

References 46 publications

Fibroblast growth factor-23 is associated with imaging markers of diabetic cardiomyopathy and anti-diabetic therapeutics

Fibroblast growth factor-23 is associated with imaging markers of diabetic cardiomyopathy and anti-diabetic therapeutics

Early renal dysfunction and fibroblast growth factor-23 in patients with small vessel disease-related stroke

Lipoprotein‐associated phospholipase A2: The story continues

Contact Info

Product

Resources

About