Prospective association of vascular endothelial growth factor-A (VEGF-A) with coronary heart disease mortality in southeastern New England.
BACKGROUND
Autopsy data suggest that plaque neovascularization may be associated with coronary heart disease (CHD) death. Since vascular endothelial growth factor-A (VEGF-A) is upregulated in angiogenesis and therefore neovascularization, we hypothesized that individuals with elevated levels of VEGF-A at baseline would be a greater risk of dying of CHD compared to those with lower levels over time.


METHODS
We measured VEGF-A levels in 46 CHD death cases and a 14% random sample of 2321 community participants who were free of self-reported CHD at baseline. Traditional CHD risk factors such as age, gender, family history of CHD, cigarette smoking, hypertension, total cholesterol/HDL ratio, diabetes mellitus, were also evaluated at baseline. Mortality follow-up was determined through linkage of baseline data with the National Death Index.


RESULTS
During a median of 13 years of follow-up, 46 subjects died of coronary heart disease. Mean VEGF-A levels were significantly higher in the CHD death cases than among the random population sample (400 pg/ml vs. 303 pg/ml, p=0.0004). In proportional hazards models adjusting for traditional risk factors, the hazard ratios (95%CI) for CHD death associated with increasing tertiles of VEGF-A were 1.0 (referent), 2.12 (0.74, 6.10), and 3.85 (1.37, 10.78), respectively (P(test for trend)=0.008).


CONCLUSIONS
In this population-based prospective, case-cohort study, baseline levels of VEGF-A showed a significant independent association with the risk of CHD death.
Eaton
Charles B
CB
Center for Primary Care and Prevention, Memorial Hospital of RI, Pawtucket, RI 02860, USA. charles_eaton@mhri.org
Gramling
Robert
R
Parker
Donna R
DR
Roberts
Mary B
MB
Lu
Bing
B
Ridker
Paul M
PM
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012237:Rhode Island / Q000453:epidemiology; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002097:C-Reactive Protein