Elevated Soluble Fms-Like Tyrosine Kinase-1 and Placental-Like Growth Factor Levels Are Associated With Development and Mortality Risk in Heart Failure

Autor: Javed Butler, W.H. Wilson Tang, Michael A. Samara, Vasiliki V. Georgiopoulou, Yuping Wu, Muhammad Hammadah, Xi Wang, Andreas P. Kalogeropoulos, Malory Weber
Rok vydání: 2016
Předmět:
Adult
Male
0301 basic medicine
medicine.medical_specialty
Time Factors
Ischemia
Kaplan-Meier Estimate
Pregnancy Proteins
030204 cardiovascular system & hematology
Coronary Angiography
Article
03 medical and health sciences
0302 clinical medicine
Predictive Value of Tests
Risk Factors
Interquartile range
Internal medicine
medicine
Animals
Humans
Prospective Studies
Endothelial dysfunction
Aged
Placenta Growth Factor
Proportional Hazards Models
Heart Failure
Vascular Endothelial Growth Factor Receptor-1
business.industry
Proportional hazards model
Hazard ratio
Middle Aged
Prognosis
medicine.disease
Confidence interval
Up-Regulation
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Endocrinology
ROC Curve
Area Under Curve
Heart failure
embryonic structures
Cardiology
Female
Cardiology and Cardiovascular Medicine
business
Biomarkers
Soluble fms-like tyrosine kinase-1
Zdroj: Circulation: Heart Failure. 9
ISSN: 1941-3297
1941-3289
DOI: 10.1161/circheartfailure.115.002115
Popis: Background— Vascular endothelial dysfunction may play an important role in the progression of heart failure (HF). We hypothesize that elevated levels of vascular markers, placental-like growth factor, and soluble Fms-like tyrosine kinase-1 (sFlt-1) are associated with adverse outcomes in patients with HF. We also assessed possible triggers of sFlt-1 elevation in animal HF models. Methods and Results— We measured plasma placental-like growth factor and sFlt-1 in 791 HF patients undergoing elective coronary angiogram. Median (interquartile range) placental-like growth factor and sFlt-1 levels were 24 (20–29) and 382 (277–953) pg/mL, respectively. After 5 years of follow-up, and after using receiver operator characteristic curves to determine optimal cutoffs, high levels of sFlt-1 (≥280 pg/mL; adjusted hazard ratio, 1.47; 95% confidence interval, 1.03–2.09; P =0.035) but not placental-like growth factor (≥25 pg/mL; adjusted hazard ratio, 1.26; 95% confidence interval, 0.94–1.71, P =0.12) were associated with adverse cardiovascular outcomes. In addition, significant elevation of sFlt-1 levels was observed in left anterior descending artery ligation and transverse aortic constriction HF mouse models after 4 and 8 weeks of follow-up, suggesting vascular stress and ischemia as triggers for sFlt-1 elevation in HF. Conclusions— Circulating sFlt-1 is generated as a result of myocardial injury and subsequent HF development. Elevated levels of sFlt-1 are associated with adverse outcomes in stable patients with HF.
Databáze: OpenAIRE
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