Atherosclerosis 151 (2000) 599
Letter to the Editor
www.elsevier.com/locate/atherosclerosis
Successful therapy reduces levels of vascular endothelial growth factor (VEGF) in patients with hypertension and patients with hypercholesterolemia
Keywords:Vascular endothelial growth factor; Hypercholesterolemia; Hypertension
We read with interest the paper by Sumino et al. [1], who reported the effect of hormone replacement therapy (HRT) on serum levels of vascular endothelial growth factor (VEGF). They suggested that HRT reduced serum levels of VEGF in normocholesterolemic (NC) post-menopausal women (PMW) with hypertension. Con-versely, HRT did not affect VEGF serum levels in the PMW with hypercholesterolemia (HC), of whom 74% were treated hypertensives.
We are concerned that their study was based on VEGF measurements in serum samples which has been shown to be inaccurate as this growth factor is released from platelets during clotting [2,3]. Indeed this may explain why some of their observations differed from our recent data.
Hypertension and HC are two of the main risk factors for the development of symptomatic atheroselerosis. We have reported raised plasma levels of VEGF in patients with peripheral artery disease and coronary artery dis-ease when compared to healthy normotensive age and sex matched controls [4]. In a pilot study, we also investi-gated the effects of antihypertensive therapy on VEGF production in 27 untreated patients (15 men, aged 54 years9S.D. 18) with essential hypertension and 27 age and sex matched healthy controls. Plasma VEGF levels in untreated hypertensive patients were significantly higher than levels in healthy normotensive controls (me-dian 130 pg/ml [IQR 10 – 2025] vs. 75 pg/ml [20 – 125] Mann – Whitney test, PB0.05). Furthermore, effective antihypertensive therapy lowered blood pressure and sig-nificantly reduced median plasma VEGF levels from 130 pg/ml [10 – 2025] to 60 pg/ml [10 – 235] after 2 months of therapy (paired Wilcoxon test,PB0.05). Sumino et al. were unable to detect a significant difference at baseline between their study group which was composed of PMW
with or without HC and hypertension (66% of the study group), when compared to the control group, which were also not clearly defined and consisted of 60% hyperten-sives. This may be attributed to the fact that hypertension itself seems to influence VEGF production, and the pro-posed efficacy in reducing VEGF with HRT in PMW with NC may in fact be a confounding effect of hyperten-sion and/or associated antihypertensive therapy rather than HRT.
We have also shown a relationship between plasma VEGF and HC. In a pilot study of 20 patients with total cholesterol of \6.0 mmol/l, and 21 healthy controls, plasma VEGF levels were significantly greater at baseline in patients with HC when compared to controls (median 222 [100 – 437] vs. 75 [25 – 11] pg/ml; PB0.05). After 3 months of lipid lowering therapy, median plasma VEGF levels had fallen significantly, to 162 [100 – 450] pg/ml; PB0.05. In contrast to the study by Sumino et al. [1], we suggest that proper management of HC leads to a reduc-tion in plasma VEGF levels, which may in turn delay or prevent the onset of symptomatic atheroselerosis.
References
[1] Sumino H, Nakamura T, Ichikawa S, et al. Serum levels of vascular endothelial growth factor is decreased by hormone re-placement therapy in postmenopausal women without hyperc-holesterolemia. Atherosclerosis 2000;148:189 – 95.
[2] Webb NIM, Bottemley MJ, Watson CJ, et al. Vascular endothe-lial growth factor (VEGF) is released from platelets during blood clotting: implications for measurement of circulating VEGF in clinical disease. Clin Sci 1998;94:395 – 404.
[3] Maloney JP, Silliman C, Ambruso DR, et al. In vitro release of vascular endothelial growth factor during platelets aggregation. Heart Circ Physiol 1998;44:H1054 – 61.
[4] Belgore FM, Lip GYH, McCollum CN, Blann AD. Vascular endothelial growth factor (VEGF) and soluble VEGF receptor (sFlt-1) levels in coronary artery disease and peripheral artery disease. Blood Coag Fibrin 1999;10 (abstract).
Funmi M. Belgore, Gregory Y.H. Lip, Andrew D. Blann Haemostasis, Thrombosis and Vascular Biology Unit, Uni6ersity Department of Medicine,
City Hospital, Birmingham B18 7QH, UK E-mail: funmib@hotmail.com
