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 journalArticlepeer-review

63 Scopus citations


Objectives: 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). Background: 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. Methods: 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. Results: 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. Conclusions: 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
Issue number4
StatePublished - Jul 19 2011


  • heart failure
  • placental growth factor
  • soluble Flt-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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