Soluble fms-like tyrosine kinase-1 and the progression of carotid intima-media thickness: 24-month follow-up study

Background: The relationship between fms-like tyrosine kinase-1 (sFlt-1), a soluble receptor for vascular endothelial growth factor (VEGF), and vascular disease has not been established, so this study aimed to elucidate the association between sFlt-1 and the progression of carotid intima - media thickness (IMT) in hypertensive patients. Methods and Results: The 120 hypertensive patients under medical control were enrolled and 112 completed the study (age 59±9 years, 57 females). Plasma VEGF and sFlt-1 levels were measured at enrollment. At baseline and 24-month visit, carotid IMT was measured and the association between sFlt-1 and IMT progression was assessed by linear regression. At baseline, age (r=0.186) and low level of high-density lipoprotein-cholesterol (HDL-C <40 mg/dl, r=0.214) were significantly related to carotid IMT. Over the 24 months, carotid IMT increased from 0.670±0.089 mm to 0.696±0.095 mm. There was a positive correlation between sFlt-1 tertiles and IMT change (P=0.05 by ANOVA). Upon multivariate analysis, log-transformed sFlt-1 level (β=0.137, P=0.003) and low HDL-C (β=0.048, P=0.04) were identified as predictors of IMT progression, independent of other confounding variables. Conclusions: High sFlt-1 level is predictive of carotid IMT progression in hypertensive patients. Low HDL-C level was also associated with IMT change. These observations support a high sFlt-1 level being indicative of progression of atherosclerosis.