The vascular marker soluble fms-like tyrosine kinase 1 is associated with disease severity and adverse outcomes in chronic heart failure.

Bonnie Ky, Benjamin French, Kosha Ruparel, Nancy K Sweitzer, James C. Fang, Wayne C. Levy, Douglas B. Sawyer, Thomas P. Cappola

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

We sought to evaluate placental growth factor (PlGF) and soluble Fms-like tyrosine kinase 1 (sFlt-1) as clinical biomarkers in chronic heart failure (HF). Vascular remodeling is a crucial compensatory mechanism in chronic HF. The angiogenic ligand PlGF and its target receptor fms-like tyrosine kinase 1 modulate vascular growth and function, but their relevance in human HF is undefined. We measured plasma PlGF and sFlt-1 in 1,403 patients from the Penn Heart Failure Study, a multicenter cohort of chronic systolic HF. Subjects were followed for death, cardiac transplantation, or ventricular assist device placement over a median follow-up of 2 years. The sFlt-1 was independently associated with measures of HF severity, including New York Heart Association functional class (p < 0.01) and B-type natriuretic peptide (p < 0.01). Patients in the 4th quartile of sFlt-1 (>379 pg/ml) had a 6.17-fold increased risk of adverse outcomes (p < 0.01). This association was robust, even after adjustment for the Seattle Failure Model (hazard ratio: 2.54, 95% confidence interval [CI]: 1.76 to 2.27, p < 0.01) and clinical confounders including HF etiology (hazard ratio: 1.67, 95% CI: 1.06 to 2.63, p = 0.03). Combined assessment of sFlt-1 and B-type natriuretic peptide exhibited high predictive accuracy at 1 year (area under the receiver-operator characteristic curve: 0.791, 95% CI: 0.752 to 0.831) that was greater than either marker alone (p < 0.01 and p = 0.03, respectively). In contrast, PlGF was not an independent marker of disease severity or outcomes. Our findings support a role for sFlt-1 in the biology of human HF. With additional study, circulating sFlt-1 might emerge as a clinically useful biomarker to assess the influence of vascular remodeling on clinical outcomes.

Original languageEnglish (US)
Pages (from-to)386-394
Number of pages9
JournalJournal of the American College of Cardiology
Volume58
Issue number4
StatePublished - Jul 19 2011
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor-1
Blood Vessels
Heart Failure
Intercellular Signaling Peptides and Proteins
Confidence Intervals
Biomarkers
Systolic Heart Failure
Heart-Assist Devices
Brain Natriuretic Peptide
Heart Transplantation
Proportional Hazards Models
Multicenter Studies
Ligands
Growth

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

The vascular marker soluble fms-like tyrosine kinase 1 is associated with disease severity and adverse outcomes in chronic heart failure. / Ky, Bonnie; French, Benjamin; Ruparel, Kosha; Sweitzer, Nancy K; Fang, James C.; Levy, Wayne C.; Sawyer, Douglas B.; Cappola, Thomas P.

In: Journal of the American College of Cardiology, Vol. 58, No. 4, 19.07.2011, p. 386-394.

Research output: Contribution to journalArticle

Ky, Bonnie ; French, Benjamin ; Ruparel, Kosha ; Sweitzer, Nancy K ; Fang, James C. ; Levy, Wayne C. ; Sawyer, Douglas B. ; Cappola, Thomas P. / The vascular marker soluble fms-like tyrosine kinase 1 is associated with disease severity and adverse outcomes in chronic heart failure. In: Journal of the American College of Cardiology. 2011 ; Vol. 58, No. 4. pp. 386-394.
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abstract = "We sought to evaluate placental growth factor (PlGF) and soluble Fms-like tyrosine kinase 1 (sFlt-1) as clinical biomarkers in chronic heart failure (HF). Vascular remodeling is a crucial compensatory mechanism in chronic HF. The angiogenic ligand PlGF and its target receptor fms-like tyrosine kinase 1 modulate vascular growth and function, but their relevance in human HF is undefined. We measured plasma PlGF and sFlt-1 in 1,403 patients from the Penn Heart Failure Study, a multicenter cohort of chronic systolic HF. Subjects were followed for death, cardiac transplantation, or ventricular assist device placement over a median follow-up of 2 years. The sFlt-1 was independently associated with measures of HF severity, including New York Heart Association functional class (p < 0.01) and B-type natriuretic peptide (p < 0.01). Patients in the 4th quartile of sFlt-1 (>379 pg/ml) had a 6.17-fold increased risk of adverse outcomes (p < 0.01). This association was robust, even after adjustment for the Seattle Failure Model (hazard ratio: 2.54, 95{\%} confidence interval [CI]: 1.76 to 2.27, p < 0.01) and clinical confounders including HF etiology (hazard ratio: 1.67, 95{\%} CI: 1.06 to 2.63, p = 0.03). Combined assessment of sFlt-1 and B-type natriuretic peptide exhibited high predictive accuracy at 1 year (area under the receiver-operator characteristic curve: 0.791, 95{\%} CI: 0.752 to 0.831) that was greater than either marker alone (p < 0.01 and p = 0.03, respectively). In contrast, PlGF was not an independent marker of disease severity or outcomes. Our findings support a role for sFlt-1 in the biology of human HF. With additional study, circulating sFlt-1 might emerge as a clinically useful biomarker to assess the influence of vascular remodeling on clinical outcomes.",
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AU - French, Benjamin

AU - Ruparel, Kosha

AU - Sweitzer, Nancy K

AU - Fang, James C.

AU - Levy, Wayne C.

AU - Sawyer, Douglas B.

AU - Cappola, Thomas P.

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