FGF-23 correlates with endocrine and metabolism dysregulation, worse cardiac and renal function, inflammation level, stenosis degree, and independently predicts in-stent restenosis risk in coronary heart disease patients underwent drug-eluting-stent PCI

Abstract

Background The present study aimed to assess the correlation of fibroblast growth factor (FGF)-23 expression with clinical characteristics, then further explore its value in predicting 2-year in-stent restenosis (ISR) risk in coronary heart disease (CHD) patients underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Methods In this prospective, single-center, observational study, totally 214 CHD patients treated by PCI with DES were consecutively recruited, and peripheral blood samples were collected prior to PCI with DES for serum samples isolation. Following, FGF-23 level in the serum samples was detected via enzyme linked-immuno-sorbent Assay. The follow-up coronary angiography was performed at 1 year and 2 years after PCI or if suspected ISR symptoms occurred. Results FGF-23 was positively correlated with fasting blood-glucose, insulin resistance, serum creatinine, serum uric acid, LDL-C, high-sensitivity C-reactive protein, cardiac troponin I and N-terminal-proB-type natriuretic peptide, while was negatively associated with HDL-C and left ventricular ejection fraction (all P < 0.01). Furthermore, FGF-23 was positively correlated with hypercholesteremia, hyperuricemia and family history of CAD (all P < 0.05). However, it did not correlate with other chronic complications, biochemical indexes, lesion features or PCI parameters (all P > 0.05). Moreover, FGF-23 level was higher in 2-year ISR patients (n = 38) compared to 2-year non-ISR patients (n = 176) (P < 0.001), and receiver operating characteristic curve indicated that FGF-23 was of good value in predicting 2-year ISR risk (AUC 0.828, 95% CI 0.761–0.896). Conclusion FGF-23 correlates with endocrine and metabolism dysregulation, worse cardiac and renal function, inflammation level, stenosis degree of target lesion, and serves as an independent risk factor for 2-year ISR risk in CHD patients underwent PCI with DES.

[Retracted] Predictive Value of Perioperative Cytokine Levels on the Risk for In‐Stent Restenosis in Acute Myocardial Infarction Patients

“…In-stent restenosis is a common risk in acute myocardial infarction patients undergoing PCI [ 10 ]. Because of the vulnerability of the artery after stent placement and the effect of endothelial regeneration, the stent site presents remarkable neointimal hyperplasia, which can lead to endothelial cell dysfunction, ectopic proliferation, and vascular smooth muscle cell migration as well as a series of inflammatory reactions.…”

An Overview of FGF-23 as a Novel Candidate Biomarker of Cardiovascular Risk

“…FGF-23 is an early and complementary predictor of adverse cardiac events and could be suitable for improving risk assessment in vulnerable patients with HF or reduced ejection fraction (Koller et al, 2015). FGF-23 is positively correlated with but does not directly depend on the classical biomarkers of cardiac damage, such as N-terminal-pro-B-type natriuretic peptide (NT-proBNP) (Seiler et al, 2011;Shibata et al, 2013;Kestenbaum et al, 2014;Poelzl et al, 2014;Koller et al, 2015;Masson et al, 2015;Panwar et al, 2015;Speer et al, 2015;Wohlfahrt et al, 2015;Ter Maaten et al, 2018;von Jeinsen et al, 2019;Song et al, 2021), high-sensitive cardiac troponin T (hs-cTnT) (Kestenbaum et al, 2014;Masson et al, 2015;Song et al, 2021) and C-reactive protein (CRP) (Parker et al, 2010;Seiler et al, 2011;Ix et al, 2012;Lutsey et al, 2014;Panwar et al, 2015;Speer et al, 2015;Reindl et al, 2017;Song et al, 2021). Furthermore, it has already been demonstrated that the predictive value of the combination of these biomarkers on cardiovascular risk assessment is significantly greater than any of them alone (Wohlfahrt et al, 2015).…”

“…Nevertheless, the meta-analysis by Marthi et al (2018) did not find a trend across different levels of kidney function in the association between high FGF-23 and HF. From a cardiac functional point of view, many studies have correlated high plasma levels of FGF-23 with a reduced left ventricular ejected fraction (LVEF; <40%), which indicates that high FGF-23 levels are directly linked to systolic dysfunction (Seiler et al, 2011;Shibata et al, 2013;Agarwal et al, 2014;Poelzl et al, 2014;von Jeinsen et al, 2019;Song et al, 2021). Furthermore, high plasma levels of FGF-23 are also associated with albuminuria in CKD which is strongly associated with Heart Failure with reduced Ejection Fraction (HFrEF), but not with Heart Failure with preserved Ejection Fraction (HFpEF) (Nayor et al, 2017).…”

“…These mineral disturbances are classic complications in CKD, but in the last few decades, it has been shown that they also have a huge impact on cardiac tissue (Figure 1) because they have direct and indirect cardiotoxic effects, such as the development of LVH, HF or arrhythmias like AF (Navarro-García et al, 2018). In relation to kidney disease, high plasma levels of FGF-23 have also been associated with impaired kidney function as represented by an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 (Parker et al, 2010;Seiler et al, 2011;Ix et al, 2012;Shibata et al, 2013;Ärnlöv et al, 2013a,b;Agarwal et al, 2014;Brandenburg et al, 2014;Kestenbaum et al, 2014;Lutsey et al, 2014;Poelzl et al, 2014;Wright et al, 2014;Koller et al, 2015;Panwar et al, 2015;Speer et al, 2015;Wohlfahrt et al, 2015;Souma et al, 2016;Ter Maaten et al, 2018;von Jeinsen et al, 2019;Patel et al, 2020;Sharma et al, 2020) and high levels of creatinine (Taylor et al, 2011;Ix et al, 2012;Shibata et al, 2013;Ärnlöv et al, 2013a;Agarwal et al, 2014;Kestenbaum et al, 2014;Wright et al, 2014;Koller et al, 2015;Masson et al, 2015;Panwar et al, 2015;Speer et al, 2015;Souma et al, 2016;Sharma et al, 2020;Song et al, 2021). di Giuseppe et al 2014; …”

“…Two of the major comorbidities that contribute to the development of cardiovascular disease are diabetes and hypertension, both of which now have a high prevalence (Ruilope, 2012;Strain and Paldanius, 2018). Recent studies have associated elevated plasma levels of FGF-23 with a higher prevalence of diabetes mellitus (Parker et al, 2010;Ix et al, 2012;Agarwal et al, 2014;Kestenbaum et al, 2014;Lutsey et al, 2014;Wright et al, 2014;Panwar et al, 2015;Speer et al, 2015;Wohlfahrt et al, 2015;Sharma et al, 2020;Song et al, 2021) and hypertension (Ix et al, 2012;Agarwal et al, 2014;Kestenbaum et al, 2014;Lutsey et al, 2014;Wright et al, 2014;Masson et al, 2015;Patel et al, 2020;Sharma et al, 2020). Some studies have demonstrated a reduction in soluble Klotho levels in patients with impaired fasting glucose (Zhang and Liu, 2018), together with increased levels of FGF-23 (Zaheer et al, 2017) in diabetic patients compared to healthy volunteers, even with preserved kidney function.…”