Abstract 14218: Soluble Vascular Endothelial Growth Factor Receptor-1 Serves as a Marker of Cardiovascular Risk in Chronic Kidney Disease Patients
Background: Vascular endothelial growth factor (VEGF) plays a key role not only in angiogenesis but also in endothelial integrity. The soluble form of VEGF receptor-1 (sVEGFR-1/sFlt-1) is an endogenous inhibitor of VEGF. A recent study demonstrated that increased sFlt-1 levels are associated with endothelial dysfunction in chronic kidney disease (CKD). However, it is unknown whether increased sFlt-1 levels predict cardiovascular events in patients with or without CKD.
Methods: We performed a prospective cohort study involving 513 consecutive stable outpatients with (CKD+: estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) or without CKD (CKD-). Patients were followed up over 3 years. The primary outcome was major adverse cardiac events (MACEs) defined as all-cause mortality, hospitalization due to acute coronary syndrome, stroke, congestive heart failure, aortic disease, and coronary and peripheral revascularization. The optimal cut-off value of sFlt-1 was determined employing receiver operating characteristic curve analysis.
Results: The median follow-up was 860 (IQR: 372-1,080) days. MACEs developed in a total of 65 patients (12.7%). Patients were divided into four groups: CKD-/low sFlt-1 (<110 pg/mL) (n=334, 60±12 y, male: 45%), CKD-/high sFlt-1 (>=110 pg/mL) (n=83, 66±13 y, male: 60%), CKD+/low in sFlt-1 (n=58, 71±8 y, male: 62%), and CKD+/high sFlt-1 (n=38, 71±8 y, male: 71%). The eGFR was similar between CKD-/low sFlt-1 (81±15) and CKD-/high sFlt-1 (82±16), and between CKD+/low sFlt-1 (48±9) and CKD+/high sFlt-1 (46±13). However, the MACE rate was significantly higher in CKD+/high sFlt-1 (40%) than in CKD+/low sFlt-1 (17%), CKD-/high sFlt-1 (16%), and CKD-/low sFlt-1 (8%). After adjusting for traditional risk factors including age, a male gender, and the presence of hypertension, diabetes, dyslipidemia, and obesity, the hazard ratios (95%CI) of CKD-/high sFlt-1, CKD+/low sFlt-1, and CKD+/high sFlt-1 relative to CKD-/low sFlt-1 were 1.3 (0.6-2.7), 1.2 (0.5-2.6), and 4.4 (2.2-8.7, P<0.0001), respectively.
Conclusions: These findings demonstrate that high sFlt-1 levels and CKD synergistically increase the risk of cardiovascular events, and provide the first evidence for sFlt-1 as a predictive marker in CKD patients.
- © 2011 by American Heart Association, Inc.