Association of soluble Flt-1 with heart failure and cardiac morphology: The MESA angiogenesis study

Cecilia Berardi, David A. Bluemke, Brian A. Houston, Todd M. Kolb, João A. Lima, Theo Pezel, Ryan J. Tedford, Samuel G. Rayner, Richard K. Cheng, Peter J. Leary

Research output: Contribution to journalArticlepeer-review


Background: Soluble Fms-like tyrosine kinase 1 (sFlt-1) may inhibit angiogenesis. Higher levels of sFlt-1 are associated with worse prognosis in prevalent heart failure patients. The aim of this study was to better understand the role of sFlt-1 in heart failure pathogenesis by characterizing relationships between sFlt-1, cardiac morphology, and the composite outcome of incident heart failure or cardiovascular (CV) death in in a multiethnic cohort free of CV disease at baseline. Methods: sFlt-1 was measured in 1,381 participants in the Multi-Ethnic Study of Atherosclerosis Angiogenesis sub-study. Linear regression was used to estimate the association between sFlt-1 and cardiac morphology and Cox proportional hazard regression was used to estimate associations with incident heart failure or CV mortality. Results: Over a median follow-up of 13.1 years, higher sFlt-1 levels were associated with incident heart failure or CV mortality independent from CV risk factors or NT-proBNP levels (HR 1.17, 95% CI 1.10-1.26, p < 0.001). Higher sFlt-1 levels were also associated with greater baseline left ventricular (LV) mass by cardiac MRI and increased loss of LV mass over the 10 years following the baseline exam (p-value 0.02 for each), but this association was no longer statistically significant after adjustment for baseline NT-proBNP (p = 0.11 and 0.10 respectively). Conclusions: Baseline sFlt-1 levels are associated with incident heart failure and cardiovascular mortality independent of traditional CV risk factors or NT-proBNP. An association was also found with cardiac mass but was no longer significant after adjustment for NT-proBNP.

Original languageEnglish (US)
Pages (from-to)619-625
Number of pages7
JournalJournal of Heart and Lung Transplantation
Issue number5
StatePublished - May 2022
Externally publishedYes


  • heart failure
  • left ventricular mass, mortality
  • soluble Fms-like tyrosine kinase 1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Transplantation
  • Pulmonary and Respiratory Medicine
  • Surgery


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