P0892PROFILE OF FIBROBLAST GROWTH FACTOR 23 IN CHRONIC KIDNEY DISEASE IN INDIAN POPULATION

Abstract Background Chronic kidney disease (CKD) is a complex disease. Recent discovery that fibroblast growth factor 23 (FGF23) play a major role in development of CKD related bone mineral disorder (BMD) indicated a paradigm shift in our understanding of CKD–BMD. Recent research indicates that higher levels of FGF23 are associated with rapid progression of CKD and higher mortality in CKD patients. It is found that FGF23 level in blood is elevated significantly early in the course of CKD, even before a rise in parathyroid hormone (PTH) level which could contribute directly to tissue injury in heart, blood vessels and kidneys, apart from just being a marker of adverse outcome, and this needs further research. The dietary habits, especially phosphate intake is likely to be different in Indian CKD population compared to western CKD population. Aims and objectives Method This is an observational study on 75 consecutive patients visiting Apollo hospital nephrology OPD in Chennai, India from June 2015 to Nov 2015. FGF23 level were determined simultaneously with serum creatinine, albumin, Vitamin D level, serum calcium, phosphate and serum PTH level done on enrolment. Serum samples when not immediately processed, were stored at -20oC. Results The age of the patient population varied from 19 to 80 years, mean 53.33 yrs with a SD of 15.49. 57(76%) were males and 18(24%) females. In our study, 46.7%patients belonged to CKD stage 4 while CKD stage 3 and 5 had 25.3% and 28% among the study population respectively. The mean FGF23 level in study population was 154.82pg/ml (Normal range 11-48.6 pg/ml). Though the FGF23 values in stage 5 CKD were higher than those in stage 3 and 4 CKD, the difference was not statistically significant (p=0.74). In our study, 63 patients (84%) had high FGF23 level and 56(74.7%) patients were already on phosphate binding drugs and PTH suppressing drugs like vit D or cinacalcet for at least 2 months. 48(85.7%) patients of those on medications and 15 (79%) of those not on medications had high FGF23 level (P value -0.48, Yates P value-0.739). In our study, PTH had an inverse correlation with eGFR and the association was statistically significant (P value 0.001). Serum Phosphorus level had an inverse correlation with eGFR and the association was statistically significant (P value 0.0001). Correlation of FGF23 values with eGFR was negative which was expected as the FGF23 levels increased with decreasing eGFR, but the association was not statistically significant. Similar results were obtained when FGF23 values were studied for association with serum calcium levels where the P value was 0.359 which was not statistically significant. Similarly, vit D levels had a negative association with P value of 0.077 and PTH levels had a positive association with P value of 0.987 (No statistical significance). Similarly, FGF23 levels and phosphate levels had a positive association without statistical significance(p= 0.224). Conclusion In conclusion, our data indicate that the rise of serum FGF23 levels in progressive Indian CKD patients is a common finding in CKD stage 3 and beyond.

Download Full-text

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

Clinical Kidney Journal ◽

10.1093/ckj/sfz081 ◽

2019 ◽

Cited By ~ 1

Author(s):

Michael Freundlich ◽

Carlos Cuervo ◽

Carolyn L Abitbol

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Volume Expansion ◽

Mineral Metabolism ◽

Fibroblast Growth Factor 23 ◽

Experimental Studies ◽

Young Patients ◽

Positive Association ◽

Fibroblast Growth ◽

Ckd Stage

AbstractBackgroundExperimental 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.

Download Full-text

Abstract P349: Association Of Fibroblast Growth Factor 23 With Incident Cardiovascular Disease And All-Cause Mortality In The Framingham Heart Study

Circulation ◽

10.1161/circ.129.suppl_1.p349 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Robin Haring ◽

Ramachandran S Vasan ◽

Henri Wallaschofski ◽

Lisa Sullivan ◽

Danielle Enserro

Keyword(s):

Cardiovascular Disease ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Regression Models ◽

Cox Regression ◽

Fibroblast Growth Factor 23 ◽

Positive Association ◽

Fibroblast Growth ◽

All Cause Mortality ◽

Incident Cardiovascular Disease

Objective: To investigate the association of fibroblast growth factor 23 (FGF23) with incident cardiovascular disease (CVD) and mortality risk in the general population. Methods: We evaluated 3,236 Framingham Offspring and Omni Study participants to examine the associations of serum FGF23 (measured by immunoassay) with 10-year incident CVD (N = 2,823) and all-cause mortality (N = 3,223) using multivariable Cox regression models. Results: During a median follow-up time of 10.8 years (Q1, 10.0; Q3, 11.4), 347 participants developed new-onset CVD and 412 died. Age- and sex-adjusted Cox regression models revealed a positive association of FGF23 with incident CVD (hazard ratio (HR) per unit increase in logFGF23: 1.43, 95% confidence interval (CI) 1.11-1.84) and all-cause mortality (HR 2.26, 95% CI, 1.86-2.75). After multivariable adjustment, the association of FGF23 with incident CVD was rendered non-significant (HR 1.12, 95% CI 0.86-1.46), whereas the positive association of FGF23 with all-cause mortality was maintained (HR: 1.87, 95% CI: 1.52 - 2.29). Analyses modeling FGF23 quartiles yielded similar findings (multivariable-adjusted HR Q4 vs. Q1 for incident CVD: 1.17, 95% CI: 0.87 - 1.59; for death: 1.87, 95% CI: 1.38 - 2.53). Conclusion: In our large community-based sample, serum FGF23 shows an independent positive association with all-cause mortality, but not with incident CVD risk.

Download Full-text

Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

Cardiorenal Medicine ◽

10.1159/000440984 ◽

2015 ◽

Vol 6 (1) ◽

pp. 73-82 ◽

Cited By ~ 9

Author(s):

Shahanas Chathoth ◽

Samir Al-Mueilo ◽

Cyril Cyrus ◽

Chittibabu Vatte ◽

Awatif Al-Nafaie ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Growth Factor ◽

Kidney Disease ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Control Group ◽

Phosphorus Metabolism ◽

Fibroblast Growth ◽

Saudi Population ◽

Fgf23 Level

Background: The osteocyte-derived hormone, fibroblast growth factor 23 (FGF23), regulates the phosphorus metabolism and suppresses 1,25-dihydroxyvitamin D production, thereby mitigating hyperphosphatemia in patients with renal disorders. An elevated FGF23 level is suggested to be an early biomarker of altered phosphorus metabolism in the initial stages of chronic kidney disease (CKD) and acts as a strong predictor of mortality in dialysis patients. In the Saudi population, there is no report on the FGF23 level in CKD patients to date. This study aims to estimate the plasma FGF23 levels in the Saudi population and to correlate it with its clinical manifestations in order to ascertain its role in the pathogenesis of CKD patients. Methods: The FGF23 level in the plasma samples was determined using ELISA in a diverse cohort of 89 cases with stage 3-5 CKD and 100 healthy subjects. The plasma FGF23 level was correlated with other biochemical parameters. Results: The results revealed that the FGF23 level was markedly elevated among CKD patients compared to the control group, and a significant inverse correlation was observed between the FGF23 level and glomerular filtration rate. FGF23 elevation was approximately 40-fold among stage 5 patients compared to the control, while the elevation of phosphate, parathyroid hormone (PTH) and alkaline phosphatase was 2-, 3- and 8-fold in this stage, respectively. Conclusion: Elevated FGF23 levels may have a strong correlation with the disease pathogenesis. In addition, FGF23 might be a future therapeutic target to intervene against the progression of CKD as well as to increase patient survivability.

Download Full-text

Correlation of CRP level with glycemic control in diabetic foot patients and its sequelae

International Surgery Journal ◽

10.18203/2349-2902.isj20175400 ◽

2017 ◽

Vol 4 (12) ◽

pp. 4006

Author(s):

Anand A. ◽

Maragathamani .

Keyword(s):

Blood Sugar ◽

Diabetic Foot ◽

Public Health Problem ◽

Positive Association ◽

Final Analysis ◽

Lower Limbs ◽

P Value ◽

Major Public Health Problem ◽

Cross Sectional ◽

Study Population

Background:Diabetes mellitus is a major public health problem globally and in Indian population and diabetic foot is reported as the most common cause of non-traumatic amputation of the lower limbs in India. There is renewed interest in various inflammatory markers and their association with various chronic complications of diabetes mellitus. There is a scarcity of data on the subject in Indian population.Methods: The current study was a cross sectional study of 100 patients admitted to a Diabetic foot in Department of General Surgery, Stanley medical college and Hospital between January 2012-November 2012. The CRP level and fasting and plasma glucose levels were considered as the relevant variables for statistical analysis.Results:A total of 100 patients were included in the final analysis. The proportion of subjects with Wagners, grade 1, grade 2, 3, 4 and 5 ulcers were 48%, 27%, 16%, 3% and 6% respectively. Among the study population, 73% of patients had CRP value greater than 40 and 27% patients had CRP value less than 40. The proportion of subjects with Higher CRP level (>40) showed increasing trend with increasing level of fasting blood sugar and post prandial blood sugar in the study population. The proportion of people who underwent amputation was 27.5% in people with CRP value >40 and it was only 6.85% of people with CRP value <40, the association between CRP values and amputation was statistically significant. (P value 0.046).Conclusions:The study has established a strong positive association between poor blood sugar control and elevated CRP levels in the study population. The study has also documented a positive association between higher CRP levels and amputation.

Download Full-text

Profile of Cell-Derived Microparticles (C-MP) in ITP: Red Cell Microparticles (RMP) Correlate with Severity of ITP.

Blood ◽

10.1182/blood.v108.11.1087.1087 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1087-1087

Author(s):

Vincenzo Fontana ◽

Pamela Dudkiewicz ◽

Eugene Ahn ◽

Wenche Jy ◽

Lawrence L. Horstman ◽

...

Keyword(s):

Statistical Significance ◽

Annexin V ◽

Inverse Correlation ◽

Intravenous Immunoglobulins ◽

Mean Value ◽

P Value ◽

Clotting Factors ◽

Anionic Phospholipids ◽

The Mean ◽

Sensitive Marker

Abstract BACKGROUND: The roles of cell-derived microparticles (C-MP) released from platelets (PMP), endothelial cells (EMP), leukocytes (LMP) and red cells (RMP) in hemostasis, thrombosis and inflammation have been appreciated in recent years. Although PMP were shown to be hemostatically active, the roles of other C-MP, especially RMP, have not been studied in ITP. We investigated C-MP in patients with ITP. MATERIAL AND METHODS: One-hundred-six patients with ITP were studied. They consisted of 73 pts with active ITP (ITP-A, 30M/43F, mean age 53.8 yr) and 33 pts in remission (ITP-R, 4M/29F, mean age 53.4 yr). ITP-A was defined by plt count <140,000 for >3 months; ITP-R was defined by plt count >140,000 for >3 months. Mean plt counts was 78,000 for ITP-A and 224,000 for ITP-R. The two groups were similar in ages. CBC with plt count, aPTT and activities of FVIII, FIX, FXI, were measured. Using flow cytometry, PMP were identified by CD41+, EMP by CD31+/CD41−, LMP by CD45+, and RMP by glycophorin+. Effects of intravenous immunoglobulins (IVIG) on C-MP were also evaluated. RESULTS: There was a strong inverse correlation between plt counts and RMP (p=0.002). RMP were higher when plt counts were lower. A significant correlation was found between platelet counts and PMP (p<0.0001) and EMP (p<0.0001), but not LMP (p>0.05). The mean value of RMP was higher in ITP-A than ITP-R (p= 0.009). Conversely, PMP and EMP were higher in ITP-R (P<0.0001). No difference was found in LMP. FVIII and IX were higher in ITP-A than ITP-R (p=0.006, p=0.001, respectively).The aPTT was shorter and FXI higher in ITP-A but they did not reach statistical significance. Only RMP (not PMP, EMP or LMP) correlated with elevated factors VIII, IX and XI (P=0.005, 0.001 and 0.005 respectively) and inversely correlated with aPTT (p=0.009). Infusion of IVIG reduced RMP (RMP pre/post=1519/1018), not the other C-MP, in 9 pts DISCUSSION/CONCLUSIONS: (i) RMP inversely correlated with plt counts and appear to be a sensitive marker of severity of ITP. However mechanisms of RMP generation, their reduction following IVIG and their roles remain to be elucidated. (ii) Among C-MP, only RMP, not other C-MP, were associated with shortening aPTT and elevated FVIII, IX, XI. (iii) RMP are positive for annexin V, providing anionic phospholipids for clotting factors and generating thrombin (data not shown). These findings suggest that RMP associated with these factors are involved in hemostasis to prevent bleeding in severe ITP. Table 1. ITP-A ITP-R p-value No. Patients 73 33 Plt count 78,000 224,000 <0.0001 C-MP: PMP 8074 16403 <0.0001 EMP 292 667 <0.0001 LMP 1718 1705 n. s. RMP 2292 1505 <0.01 Coag: aPTT 24.9 25.7 n. s. FVIII 1.95 1.50 0.006 FIX 1.53 1.28 0.001 FXI 1.29 1.12 n.s.

Download Full-text

The association of circulating ferritin with serum concentrations of fibroblast growth factor-23 measured by three commercial assays

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/000456307781646102 ◽

2007 ◽

Vol 44 (5) ◽

pp. 463-466 ◽

Cited By ~ 51

Author(s):

Brian H Durham ◽

Frank Joseph ◽

Lisa M Bailey ◽

William D Fraser

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Serum Ferritin ◽

Fibroblast Growth Factor 23 ◽

Inverse Correlation ◽

Biologically Active ◽

Enzyme Linked Immunosorbent Assay ◽

Fibroblast Growth ◽

Serum Samples ◽

Fgf 23

Background: The measurement of the serum concentration of fibroblast growth factor-23 (FGF-23) is beginning to be used as a diagnostic tool in renal phosphate wasting disorders. Having observed an increased serum FGF-23 in three subjects with low circulating ferritin concentrations we investigated the association between low ferritin and raised serum FGF-23. Methods: We measured FGF-23 in 150 random anonymized serum samples with ferritin concentrations between <5 and 50 µg/L using three commercially available enzyme-linked immunosorbent assay (ELISA) kits. One kit, Human FGF-23[C-term] (Immutopics Inc, USA) measures total FGF-23 whereas the other two kits, Immutopics intact and FGF-23 ELISA (Kainos, Japan) are reported to measure only the biologically active intact molecule. Results: We have detected a significant inverse correlation of -0.565 ( P<0.0001) between serum ferritin when <50 µg/L and FGF-23 using the C-terminal assay. This relationship is also shown with the Immutopics intact assay but is not demonstrated with the Kainos intact assay. Conclusion: The measurement of FGF-23 by both Immutopics assays is altered in the presence of low circulating concentrations of serum ferritin whereas with the Kainos intact assay this effect was not demonstrated. Serum ferritin should be measured when an elevated FGF-23 is obtained using the Immutopics C-terminal or intact FGF-23 assay to prevent misdiagnosis of the cause of this abnormality.

Download Full-text

SUN-059 Significance of fibroblast growth factor-23 (FGF23) level in hemodialysis patients

Kidney International Reports ◽

10.1016/j.ekir.2019.05.455 ◽

2019 ◽

Vol 4 (7) ◽

pp. S179

Author(s):

M. Tashiro ◽

H. Shima ◽

T. Inoue ◽

K. Kawahara ◽

K. Miya ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Hemodialysis Patients ◽

Fibroblast Growth ◽

Fgf23 Level

Download Full-text

Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz266 ◽

2020 ◽

Vol 36 (1) ◽

pp. 121-128 ◽

Cited By ~ 1

Author(s):

Maarten A De Jong ◽

Michele F Eisenga ◽

Adriana J van Ballegooijen ◽

Joline W J Beulens ◽

Marc G Vervloet ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Fibroblast Growth Factor 23 ◽

Population Based ◽

Fibroblast Growth ◽

Fgf23 Level ◽

Increased Risk ◽

All Cause Mortality ◽

New Onset

Abstract Background Fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone that increases early in the course of chronic kidney disease (CKD), is associated with disease progression in patients with established CKD. Here we aimed to investigate the association between plasma FGF23 and new-onset CKD in the general population. Methods We included 5253 individuals without CKD who participated in the Prevention of Renal and Vascular Endstage Disease study, a prospective, population-based cohort. Multi-variable Cox regression was used to study the association of plasma C-terminal FGF23 with new-onset CKD, defined as a combined endpoint of estimated glomerular filtration rate (eGFR) <60 mL/min/ 1.73 m2, urinary 24-h albumin excretion (UAE) >30 mg/24 h or both, or with all-cause mortality. Results The median baseline FGF23 was 68 [interquartile range (IQR) 56–85] RU/mL, eGFR was 95 ± 13 mL/min/1.73 m2 and UAE was 7.8 (IQR 5.8–11.5) mg/24 h. After follow-up of 7.5 (IQR 7.2–8.0) years, 586 participants developed CKD and 214 participants died. A higher FGF23 level was associated with new-onset CKD, independent of risk factors for kidney disease and parameters of bone and mineral homoeostasis {fully adjusted hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.10–1.44] per doubling of FGF23; P = 0.001}. In secondary analyses, FGF23 was independently associated with new-onset eGFR <60 mL/min/1.73 m2 [adjusted HR 1.28 (95% CI 1.00–1.62); P = 0.048] or with UAE >30 mg/24 h [adjusted HR 1.24 (95% CI 1.06–1.45); P = 0.01] individually. A higher FGF23 level was also associated with an increased risk of all-cause mortality [fully adjusted HR 1.30 (95% CI 1.03–1.63); P = 0.03]. Conclusions High FGF23 levels are associated with an increased risk of new-onset CKD and all-cause mortality in this prospective population-based cohort, independent of established CKD risk factors.

Download Full-text

Understanding of intra-operative tourniquets amongst orthopaedic surgeons and theatre staff – a questionnaire study

Annals of The Royal College of Surgeons of England ◽

10.1308/003588410x1251883644060 ◽

2010 ◽

Vol 92 (3) ◽

pp. 243-245 ◽

Cited By ~ 7

Author(s):

Amir Sadri ◽

Ian J Braithwaite ◽

Hani B Abdul-Jabar ◽

Khaled M Sarraf

Keyword(s):

Orthopaedic Surgery ◽

Improve Patient Safety ◽

Statistical Significance ◽

P Value ◽

Medical Practitioners ◽

Theatre Staff ◽

Study Population ◽

Bloodless Field ◽

The Mean ◽

Improve Patient

INTRODUCTION Pneumatic tourniquets are used frequently in orthopaedic theatres to provide a bloodless field whilst operating on the extremities. Their use has given rise to complications and preventable damage due to over-pressurisation and prolonged application. We designed a questionnaire to assess the knowledge on tourniquet use among operating department assistants (ODAs) and specialist registrars (SpRs) in orthopaedic surgery. SUBJECTS AND METHODS A questionnaire was constructed using set guidelines from the Association of periOperative Registered Nurses (AORN) for recommended practice of tourniquet application. This was distributed to orthopaedic registrars with varying levels of experience and ODAs from five different NHS hospitals. The unpaired, two tailed t-test was used to test for statistical significance of results. RESULTS A total of 54 completed questionnaires were collected for analysis. The study population included 29 orthopaedic SpRs and 25 ODAs. The mean score for the orthopaedic SpRs as a group was 41.3% (SD 6.85; range, 29.0–54.8%). The mean score for the ODAs was 46.7% (SD 9.64; range, 23.3–62.9%) with a P-value of 0.024. CONCLUSIONS Most surgeons are taught how to use pneumatic tourniquets by their senior colleagues as no formal teaching is given. Most of the complications are infrequent and preventable. However, their consequences can be devastating to the patient with medicolegal implications. Our results show suboptimal knowledge of tourniquets and their use among SpRs and ODAs. This study highlights the need for amendments in training to improve the knowledge and awareness of medical practitioners on the application and use of tourniquets to prevent adverse events and improve patient safety.

Download Full-text

Abstract P058: Serum Fibroblast Growth Factor-23 Does Not Have a Linear Relation to Cardiovascular Mortality

Circulation ◽

10.1161/circ.131.suppl_1.p058 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Karl Krupp ◽

Emir Veledar ◽

Purnima Madhivanan ◽

Robert Cook ◽

Khurram Nasir

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Cardiovascular Mortality ◽

Meta Analysis ◽

Fibroblast Growth Factor 23 ◽

High Serum ◽

P Value ◽

Fibroblast Growth ◽

Significant Difference ◽

Cvd Mortality

Introduction: Fibroblast Growth Factor 23 (FGF23) is bone-derived hormone regulating phosphate homeostasis as part of a newly described bone-kidney axis. Several studies have demonstrated that elevated circulating FGF23 levels are independently associated with cardiovascular mortality. Methods: A systematic review was conducted according to Meta-analysis of Observational Studies in Epidemiology Group guidelines. Six databases (PubMed-Central, Ovid-MEDLINE, EMBASE, Web of Science, BIOSIS and Cochrane Database of Systematic Reviews) were searched for articles published between 2000 and 2014 examining the longitudinal association between FGF23 and CVD mortality among populations without prior CVD, Chronic Kidney Disease, or Diabetes. The review yielded 1,961 articles, of which 982 met the inclusion criteria. About 893 abstracts were excluded during the title and abstract screen, and an additional 92 after full text review. Only three articles met the review criteria and were included in the meta-analysis. Data from selected articles were abstracted and independently assessed for quality by two reviewers. Summary estimates and associated 95% confidence intervals were included in fixed and random-effects models. The presence of heterogeneity was evaluated using a Q-statistic with a conservative p-value of 0.10. All analyses were performed using R library meta. Results: Data for 15,379 participants were included in the meta-analysis. The hazard ratio for quartiles two and four when compared with quartile one,the reference category, were 1.29 (1.06- 1.58; p=0.01) and 1.31 (1.077-1.59; p=0.0068) respectively. There was no significant difference in CVD mortality between the third and first quartile. There was also no evidence of heterogeneity observed (I2 = 0%, p = 0.611). Conclusions: This study found a U-shaped association between FGF23 and CVD mortality suggesting that either low or high serum levels increase risk for CVD mortality. Current strategies focus on lowering high levels of circulating FGF23, but little attention has been given to understanding optimal levels necessary to prevent CVD mortality. If this U-shaped relationship between FGF23 and CVD mortality is real, the possible links, causes, and mechanisms require additional research.

Download Full-text