Abstract

Objective: To examine the association of serum VEGF levels with incident stroke and transient ischemic attack (TIA) in a large, community-based cohort. Background: VEGF, an endothelial growth factor promotes angiogenesis and neurogenesis and has demonstrated neuroprotective properties in animal experiments. However, high circulating VEGF levels have also been observed in patients with vascular risk factors, atherosclerosis and in small studies of acute stroke. There have been no studies examining the association of serum VEGF with the risk of stroke in a community-based sample. Methods: In 3440 stroke/TIA-free FHS participants (mean age 65+11yrs, 56%W), we related baseline VEGF (log-transformed) to risk of incident stroke/TIA. To examine the incremental utility of VEGF over age-, sex- and baseline Framingham Stroke Risk Profile (FSRP) in predicting stroke/TIA, we also calculated the net reclassification improvement (NRI). Results: During a median follow-up of 10 years, 193 participants experienced incident stroke/TIA (129 ischemic strokes). In multivariable analyses adjusted for age-, sex- and traditional stroke risk factors (as identified by the FSRP), higher logVEGF levels were associated with an increased risk of incident stroke/TIA (HR/1SD increase in logVEGF: 1.21, 95%CI: 1.04-1.40, p=0.012). This was also true for incident ischemic stroke events (HR/1SD increase in logVEGF: 1.21 95%CI: 1.01-1.44 p=0.04). In reclassification analyses, logVEGF, when added to a risk assessment model based on the FSRP resulted in significant improvement of risk prediction with NRI of 0.046 (p=0.036). Interpretation: After adjusting for traditional stroke risk factors, higher VEGF concentrations were associated with increased risk of incident stroke/TIA, suggesting that VEGF may serve as a novel risk marker for stroke/TIA and to improve risk stratification permitting more targeted preventive interventions.

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