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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Associations Between Cardiac Biomarkers and Cardiac Structure and Function in CKD
Nathan R Stein1, Leila R Zelnick2, Amanda H Anderson3
1Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Insights
In chronic kidney disease (CKD), novel biomarker growth differentiation factor 15 (GDF-15) and established cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) correlate with subclinical cardiac changes. These findings may illuminate pathways to heart failure.
Area of Science:
- Cardiology
- Nephrology
- Biomarker Research
Background:
- Subclinical cardiac structural and functional changes in chronic kidney disease (CKD) precede clinical heart failure (HF).
- Cardiac biomarkers may reflect these underlying pathophysiological alterations.
- Investigating novel biomarkers alongside established ones offers insight into CKD-related cardiovascular disease.
Purpose of the Study:
- To assess associations between established (NT-proBNP, hsTnT) and novel (GDF-15, Gal-3, sST-2) biomarkers with echocardiographic measures of cardiac structure and function in CKD patients.
- To explore the relationship between these biomarkers and subclinical cardiovascular disease in mild to moderate CKD.
Main Methods:
- Cross-sectional analysis of 2101 participants with mild to moderate CKD from the Chronic Renal Insufficiency Cohort (CRIC) study.
- Biomarker levels at baseline were correlated with echocardiographic measurements (LVMI, LVESV, LVEDV, LVEF, LAD) obtained one year later.
- Multivariable linear regression models were used to adjust for relevant covariates.
Main Results:
- Growth differentiation factor 15 (GDF-15) showed significant associations with increased left ventricular mass index (LVMI), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV).
- These GDF-15 associations were attenuated after adjusting for NT-proBNP and hsTnT.
- Established biomarkers NT-proBNP and hsTnT were significantly associated with all measured echocardiographic parameters, while Gal-3 and sST-2 showed no significant associations.
Conclusions:
- In CKD patients, GDF-15, NT-proBNP, and hsTnT are associated with echocardiographic evidence of subclinical cardiovascular disease.
- These biomarkers may collectively indicate biological pathways contributing to the progression of heart failure in CKD.
- Further research is warranted to elucidate the specific roles of these biomarkers in CKD-associated cardiotoxicity.
Introduction:
Subclinical changes to cardiac structure and function detected with echocardiography precede the development of clinical heart failure (HF) in persons with chronic kidney disease (CKD). Circulating cardiac biomarkers may reflect these pathophysiological changes. This study investigated associations between established biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP] and high-sensitivity troponin T [hsTnT]) and novel biomarkers (growth differentiation factor 15 [GDF-15], galectin-3 [Gal-3], and soluble ST-2 [sST-2]), using echocardiographic measurements in persons with CKD.
Methods:
In cross-sectional analyses among 2101 participants with mild to moderate CKD in the Chronic Renal Insufficiency Cohort (CRIC), biomarker levels measured at baseline were evaluated with echocardiographic measurements 1 year later. These included left ventricular mass index (LVMI), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), and left atrial diameter (LAD). Multivariable linear regression analyses tested associations of each biomarker with echocardiographic measurements, adjusting for covariates.
Results:
GDF-15 was significantly associated with higher LVMI (1.0 g/m2.7; 95% CI, 0.4-1.7), LVESV (0.4 ml/m2.7; 95% CI, 0.0-0.7), and LVEDV (0.6 ml/m2.7; 95% CI, 0.1-1.1), but not with LVEF or LAD. These findings were not significant when adjusting for NT-proBNP and hsTnT. Gal-3 and sST-2 had no significant associations. Higher levels of NT-proBNP and hsTnT were associated with all echocardiographic measurements.
Conclusion:
In patients with CKD, the novel biomarker GDF-15, a marker of inflammation and tissue injury, and clinical biomarkers NT-proBNP and hsTnT, were associated with echocardiographic measurements of subclinical cardiovascular disease. Collectively, these biomarkers may highlight biological pathways that contribute to the development of clinical HF.
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