Fibroblast growth factor 23, high-sensitivity cardiac troponin, and left ventricular hypertrophy in CKD

Kelsey Smith; Christopher Defilippi; Tamara Isakova; Orlando M. Gutiérrez; Karen Laliberte; Stephen Seliger; Walter Kelley; Show Hong Duh; Michael Hise; Robert Christenson; Myles Wolf; James Januzzi

doi:10.1053/j.ajkd.2012.06.022

Fibroblast growth factor 23, high-sensitivity cardiac troponin, and left ventricular hypertrophy in CKD

Kelsey Smith, Christopher Defilippi, Tamara Isakova, Orlando M. Gutiérrez, Karen Laliberte, Stephen Seliger, Walter Kelley, Show Hong Duh, Michael Hise, Robert Christenson, Myles Wolf^*, James Januzzi

^*Corresponding author for this work

Medicine, Nephrology Division

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

Background: Detectable levels of cardiac troponins are common in individuals with chronic kidney disease (CKD), even in the absence of symptomatic cardiovascular disease. Abnormal cardiac troponin values are associated with coronary artery disease and left ventricular hypertrophy (LVH) and predict poor clinical outcomes. Elevated levels of fibroblast growth factor 23 (FGF-23) contribute to LVH in CKD. We investigated the association of FGF-23 and hs-cTnI (high-sensitivity cardiac troponin I) and hs-cTnT (high-sensitivity cardiac troponin T) levels in CKD and examined the role of LVH in this association. Study Design: Cross-sectional observational study. Setting & Participants: 153 stable outpatients with non-dialysis-dependent CKD. Predictor: The primary predictor was FGF-23 level. Outcomes: hs-cTnI, hs-cTnT. Measurements: FGF-23, hs-cTnI, hs-cTnT; left ventricular mass index (LVMI) assessed by echocardiography; coronary artery calcification (CAC) measured by computed tomography. LVMI and CAC were evaluated as potential mediators of the effect of FGF-23 on hs-cTnI/T. Results: Mean age was 64 ± 12 (SD) years, mean estimated glomerular filtration rate was 34 ± 11 mL/min/1.73 m ², median FGF-23 level was 120 (25th-75th percentile, 79-223) reference unit (RU)/mL, median hs-cTnI level was 6.5 (25th-75th percentile, 3.5-14.5) pg/mL, and median hs-cTnT level was 16.8 (25th-75th percentile, 11.1-33.9) pg/mL. cTnI and cTnT concentrations were higher than the 99th percentile of a healthy population in 42% and 61% of patients, respectively. In unadjusted and multivariable-adjusted analyses, hs-cTnI/T levels were associated significantly with FGF-23 levels. Adjusting for LVMI, but not CAC, weakened the association of FGF-23 and hs-cTnI/T levels. Limitations: Vitamin D levels were not measured. The prevalence of coronary artery disease may have been underestimated because it was ascertained by self-report. Conclusions: Minimally elevated cTnI and cTnT levels, detectable by high-sensitivity assays, are associated with elevated FGF-23 levels in stable outpatients with CKD. FGF-23-associated LVH may contribute to detectable hs-cTnI/T levels observed in non-dialysis-dependent patients with CKD.

Original language	English (US)
Pages (from-to)	67-73
Number of pages	7
Journal	American Journal of Kidney Diseases
Volume	61
Issue number	1
DOIs	https://doi.org/10.1053/j.ajkd.2012.06.022
State	Published - Jan 2013

Funding

Support: Funding for the main study in patients with CKD was provided by an investigator-initiated grant from Dade Behring (now Siemens Healthcare Diagnostics) to Dr deFilippi. For the present study, all hypotheses and analyses were generated and tested by the authors independently of industry support. This study was supported by the American Society of Nephrology Student Scholars Grant (to Ms Smith) and by grants from the National Institutes of Health ( K30RR02229207 , M01RR01066 , Mallinckrodt General Clinical Research Center at Massachusetts General Hospital ; and R01DK076116 to Dr Wolf).

Keywords

Fibroblast growth factor 23
chronic kidney disease
high-sensitivity cardiac troponin
left ventricular hypertrophy

ASJC Scopus subject areas

Nephrology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1053/j.ajkd.2012.06.022

Cite this

@article{04263f1cf5dd43bdaa48aa5d5b14be5b,

title = "Fibroblast growth factor 23, high-sensitivity cardiac troponin, and left ventricular hypertrophy in CKD",

abstract = "Background: Detectable levels of cardiac troponins are common in individuals with chronic kidney disease (CKD), even in the absence of symptomatic cardiovascular disease. Abnormal cardiac troponin values are associated with coronary artery disease and left ventricular hypertrophy (LVH) and predict poor clinical outcomes. Elevated levels of fibroblast growth factor 23 (FGF-23) contribute to LVH in CKD. We investigated the association of FGF-23 and hs-cTnI (high-sensitivity cardiac troponin I) and hs-cTnT (high-sensitivity cardiac troponin T) levels in CKD and examined the role of LVH in this association. Study Design: Cross-sectional observational study. Setting & Participants: 153 stable outpatients with non-dialysis-dependent CKD. Predictor: The primary predictor was FGF-23 level. Outcomes: hs-cTnI, hs-cTnT. Measurements: FGF-23, hs-cTnI, hs-cTnT; left ventricular mass index (LVMI) assessed by echocardiography; coronary artery calcification (CAC) measured by computed tomography. LVMI and CAC were evaluated as potential mediators of the effect of FGF-23 on hs-cTnI/T. Results: Mean age was 64 ± 12 (SD) years, mean estimated glomerular filtration rate was 34 ± 11 mL/min/1.73 m 2, median FGF-23 level was 120 (25th-75th percentile, 79-223) reference unit (RU)/mL, median hs-cTnI level was 6.5 (25th-75th percentile, 3.5-14.5) pg/mL, and median hs-cTnT level was 16.8 (25th-75th percentile, 11.1-33.9) pg/mL. cTnI and cTnT concentrations were higher than the 99th percentile of a healthy population in 42% and 61% of patients, respectively. In unadjusted and multivariable-adjusted analyses, hs-cTnI/T levels were associated significantly with FGF-23 levels. Adjusting for LVMI, but not CAC, weakened the association of FGF-23 and hs-cTnI/T levels. Limitations: Vitamin D levels were not measured. The prevalence of coronary artery disease may have been underestimated because it was ascertained by self-report. Conclusions: Minimally elevated cTnI and cTnT levels, detectable by high-sensitivity assays, are associated with elevated FGF-23 levels in stable outpatients with CKD. FGF-23-associated LVH may contribute to detectable hs-cTnI/T levels observed in non-dialysis-dependent patients with CKD.",

keywords = "Fibroblast growth factor 23, chronic kidney disease, high-sensitivity cardiac troponin, left ventricular hypertrophy",

author = "Kelsey Smith and Christopher Defilippi and Tamara Isakova and Guti{\'e}rrez, {Orlando M.} and Karen Laliberte and Stephen Seliger and Walter Kelley and Duh, {Show Hong} and Michael Hise and Robert Christenson and Myles Wolf and James Januzzi",

note = "Funding Information: Support: Funding for the main study in patients with CKD was provided by an investigator-initiated grant from Dade Behring (now Siemens Healthcare Diagnostics) to Dr deFilippi. For the present study, all hypotheses and analyses were generated and tested by the authors independently of industry support. This study was supported by the American Society of Nephrology Student Scholars Grant (to Ms Smith) and by grants from the National Institutes of Health ( K30RR02229207 , M01RR01066 , Mallinckrodt General Clinical Research Center at Massachusetts General Hospital ; and R01DK076116 to Dr Wolf). ",

year = "2013",

month = jan,

doi = "10.1053/j.ajkd.2012.06.022",

language = "English (US)",

volume = "61",

pages = "67--73",

journal = "American Journal of Kidney Diseases",

issn = "0272-6386",

publisher = "W.B. Saunders",

number = "1",

}

TY - JOUR

T1 - Fibroblast growth factor 23, high-sensitivity cardiac troponin, and left ventricular hypertrophy in CKD

AU - Smith, Kelsey

AU - Defilippi, Christopher

AU - Isakova, Tamara

AU - Gutiérrez, Orlando M.

AU - Laliberte, Karen

AU - Seliger, Stephen

AU - Kelley, Walter

AU - Duh, Show Hong

AU - Hise, Michael

AU - Christenson, Robert

AU - Wolf, Myles

AU - Januzzi, James

N1 - Funding Information: Support: Funding for the main study in patients with CKD was provided by an investigator-initiated grant from Dade Behring (now Siemens Healthcare Diagnostics) to Dr deFilippi. For the present study, all hypotheses and analyses were generated and tested by the authors independently of industry support. This study was supported by the American Society of Nephrology Student Scholars Grant (to Ms Smith) and by grants from the National Institutes of Health ( K30RR02229207 , M01RR01066 , Mallinckrodt General Clinical Research Center at Massachusetts General Hospital ; and R01DK076116 to Dr Wolf).

PY - 2013/1

Y1 - 2013/1

N2 - Background: Detectable levels of cardiac troponins are common in individuals with chronic kidney disease (CKD), even in the absence of symptomatic cardiovascular disease. Abnormal cardiac troponin values are associated with coronary artery disease and left ventricular hypertrophy (LVH) and predict poor clinical outcomes. Elevated levels of fibroblast growth factor 23 (FGF-23) contribute to LVH in CKD. We investigated the association of FGF-23 and hs-cTnI (high-sensitivity cardiac troponin I) and hs-cTnT (high-sensitivity cardiac troponin T) levels in CKD and examined the role of LVH in this association. Study Design: Cross-sectional observational study. Setting & Participants: 153 stable outpatients with non-dialysis-dependent CKD. Predictor: The primary predictor was FGF-23 level. Outcomes: hs-cTnI, hs-cTnT. Measurements: FGF-23, hs-cTnI, hs-cTnT; left ventricular mass index (LVMI) assessed by echocardiography; coronary artery calcification (CAC) measured by computed tomography. LVMI and CAC were evaluated as potential mediators of the effect of FGF-23 on hs-cTnI/T. Results: Mean age was 64 ± 12 (SD) years, mean estimated glomerular filtration rate was 34 ± 11 mL/min/1.73 m 2, median FGF-23 level was 120 (25th-75th percentile, 79-223) reference unit (RU)/mL, median hs-cTnI level was 6.5 (25th-75th percentile, 3.5-14.5) pg/mL, and median hs-cTnT level was 16.8 (25th-75th percentile, 11.1-33.9) pg/mL. cTnI and cTnT concentrations were higher than the 99th percentile of a healthy population in 42% and 61% of patients, respectively. In unadjusted and multivariable-adjusted analyses, hs-cTnI/T levels were associated significantly with FGF-23 levels. Adjusting for LVMI, but not CAC, weakened the association of FGF-23 and hs-cTnI/T levels. Limitations: Vitamin D levels were not measured. The prevalence of coronary artery disease may have been underestimated because it was ascertained by self-report. Conclusions: Minimally elevated cTnI and cTnT levels, detectable by high-sensitivity assays, are associated with elevated FGF-23 levels in stable outpatients with CKD. FGF-23-associated LVH may contribute to detectable hs-cTnI/T levels observed in non-dialysis-dependent patients with CKD.

AB - Background: Detectable levels of cardiac troponins are common in individuals with chronic kidney disease (CKD), even in the absence of symptomatic cardiovascular disease. Abnormal cardiac troponin values are associated with coronary artery disease and left ventricular hypertrophy (LVH) and predict poor clinical outcomes. Elevated levels of fibroblast growth factor 23 (FGF-23) contribute to LVH in CKD. We investigated the association of FGF-23 and hs-cTnI (high-sensitivity cardiac troponin I) and hs-cTnT (high-sensitivity cardiac troponin T) levels in CKD and examined the role of LVH in this association. Study Design: Cross-sectional observational study. Setting & Participants: 153 stable outpatients with non-dialysis-dependent CKD. Predictor: The primary predictor was FGF-23 level. Outcomes: hs-cTnI, hs-cTnT. Measurements: FGF-23, hs-cTnI, hs-cTnT; left ventricular mass index (LVMI) assessed by echocardiography; coronary artery calcification (CAC) measured by computed tomography. LVMI and CAC were evaluated as potential mediators of the effect of FGF-23 on hs-cTnI/T. Results: Mean age was 64 ± 12 (SD) years, mean estimated glomerular filtration rate was 34 ± 11 mL/min/1.73 m 2, median FGF-23 level was 120 (25th-75th percentile, 79-223) reference unit (RU)/mL, median hs-cTnI level was 6.5 (25th-75th percentile, 3.5-14.5) pg/mL, and median hs-cTnT level was 16.8 (25th-75th percentile, 11.1-33.9) pg/mL. cTnI and cTnT concentrations were higher than the 99th percentile of a healthy population in 42% and 61% of patients, respectively. In unadjusted and multivariable-adjusted analyses, hs-cTnI/T levels were associated significantly with FGF-23 levels. Adjusting for LVMI, but not CAC, weakened the association of FGF-23 and hs-cTnI/T levels. Limitations: Vitamin D levels were not measured. The prevalence of coronary artery disease may have been underestimated because it was ascertained by self-report. Conclusions: Minimally elevated cTnI and cTnT levels, detectable by high-sensitivity assays, are associated with elevated FGF-23 levels in stable outpatients with CKD. FGF-23-associated LVH may contribute to detectable hs-cTnI/T levels observed in non-dialysis-dependent patients with CKD.

KW - Fibroblast growth factor 23

KW - chronic kidney disease

KW - high-sensitivity cardiac troponin

KW - left ventricular hypertrophy

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U2 - 10.1053/j.ajkd.2012.06.022

DO - 10.1053/j.ajkd.2012.06.022

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AN - SCOPUS:84871236512

SN - 0272-6386

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JO - American Journal of Kidney Diseases

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Fibroblast growth factor 23, high-sensitivity cardiac troponin, and left ventricular hypertrophy in CKD

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UN SDGs

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