TY - JOUR
T1 - Circulating vascular endothelial growth factor and the risk of cardiovascular events
AU - Kaess, Bernhard M.
AU - Preis, Sarah R.
AU - Beiser, Alexa
AU - Sawyer, Douglas B.
AU - Chen, Tai C.
AU - Seshadri, Sudha
AU - Vasan, Ramachandran S.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Objective: To investigate the relation of circulating concentrations of vascular endothelial growth factor (VEGF) for the risk of developing cardiovascular disease (CVD) in a large community-based sample. Methods: We prospectively assessed the relation of circulating VEGF concentrations with the incidence of CVD among 3041 Framingham Heart Study participants (mean age 63.4±11.1 years, 59% women). Multivariable Cox proportional hazards models were estimated adjusting for standard risk factors to VEGF quartiles to incident CVD. Restricted cubic splines were used to examine the linearity of the association. Results: After a mean follow-up of 8.8 (±2.8) years, 527 individuals experienced a first CVD event. Compared with participants in the first VEGF quartile, individuals in the second VEGF quartile had a 34% increased risk for future CVD (HR 1.34, 95% CI 1.03 to 1.74; p value=0.03) and individuals in third quartile had a 59% higher risk (HR 1.59; 95% CI 1.23 to 2.05, p value=0.0003). Individuals in the highest VEGF quartile had a similar cardiovascular risk as compared with those in the lowest VEGF quartile (HR 1.18, 95% CI 0.91 to 1.53, p value=0.21). Evaluation of restricted cubic splines confirmed the nonlinear, inverted U-shaped relation of serum VEGF and CVD events (p<0.0001 for model fit, p=0.006 for non-linearity). Conclusions: Circulating VEGF concentrations exhibit a complex non-linear (inverted U-shaped) relation with the risk of developing CVD events, with the lowest risk experienced at the lower and upper end of the distribution. The underlying pathophysiological mechanisms remain to be elucidated.
AB - Objective: To investigate the relation of circulating concentrations of vascular endothelial growth factor (VEGF) for the risk of developing cardiovascular disease (CVD) in a large community-based sample. Methods: We prospectively assessed the relation of circulating VEGF concentrations with the incidence of CVD among 3041 Framingham Heart Study participants (mean age 63.4±11.1 years, 59% women). Multivariable Cox proportional hazards models were estimated adjusting for standard risk factors to VEGF quartiles to incident CVD. Restricted cubic splines were used to examine the linearity of the association. Results: After a mean follow-up of 8.8 (±2.8) years, 527 individuals experienced a first CVD event. Compared with participants in the first VEGF quartile, individuals in the second VEGF quartile had a 34% increased risk for future CVD (HR 1.34, 95% CI 1.03 to 1.74; p value=0.03) and individuals in third quartile had a 59% higher risk (HR 1.59; 95% CI 1.23 to 2.05, p value=0.0003). Individuals in the highest VEGF quartile had a similar cardiovascular risk as compared with those in the lowest VEGF quartile (HR 1.18, 95% CI 0.91 to 1.53, p value=0.21). Evaluation of restricted cubic splines confirmed the nonlinear, inverted U-shaped relation of serum VEGF and CVD events (p<0.0001 for model fit, p=0.006 for non-linearity). Conclusions: Circulating VEGF concentrations exhibit a complex non-linear (inverted U-shaped) relation with the risk of developing CVD events, with the lowest risk experienced at the lower and upper end of the distribution. The underlying pathophysiological mechanisms remain to be elucidated.
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U2 - 10.1136/heartjnl-2015-309155
DO - 10.1136/heartjnl-2015-309155
M3 - Article
C2 - 27354275
AN - SCOPUS:84979084603
SN - 1355-6037
VL - 102
SP - 1898
EP - 1901
JO - Heart
JF - Heart
IS - 23
ER -