Relation of thrombogenesis in systemic hypertension to angiogenesis and endothelial damage/dysfunction (a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT])

Am J Cardiol. 2003 Aug 15;92(4):400-5. doi: 10.1016/s0002-9149(03)00657-x.

Abstract

Increasing evidence points toward a prothrombotic state in hypertension and atherosclerosis, conditions associated with thrombosis-related complications, such as myocardial infarction and stroke. We hypothesized that this increased risk of thrombogenesis may be related to endothelial damage/dysfunction and abnormal angiogenesis, and thus, an increased risk of future cardiovascular disease. Thrombogenesis, endothelial damage/dysfunction, and angiogenesis can be assessed by measurement of tissue factor (TF), von Willebrand Factor (vWF), flow-mediated dilatation (FMD), and vascular endothelial growth factor (VEGF), respectively. To test this hypothesis, we measured TF, vWF, FMD, and VEGF in 76 patients with systemic hypertension (71 men; mean age 64; mean blood pressure 167/72 mm Hg), considered additional risk factors such as diabetes, and related them to the patient's 10-year cardiovascular and cerebrovascular risk score using the Framingham equation. Patients were compared with 48 healthy normotensive controls. In these patients, the effects of 6 months of intensified blood pressure and (where appropriate) lipid-lowering treatment were investigated. In our patients, TF, VEGF, and vWF levels were higher, but FMD was lower (all p <0.001) compared with the controls. All markers correlated with each other and with both cardiovascular and cerebrovascular risk scores (all p <0.001). After intensified blood pressure and hypercholesterolemia treatment, total cholesterol, blood pressure, TF, VEGF, and vWF levels all decreased, whereas FMD increased (all p <0.001). Thus, in subjects with hypertension and other risk factors, endothelial damage/dysfunction (and thus, atherogenesis), thrombogenesis, and angiogenesis are abnormal, correlate with overall cardiovascular risk, and importantly, can be related to each other in a "Birmingham Vascular Triangle." Furthermore, these processes are beneficially affected by intensive blood pressure and lipid treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arteriosclerosis / blood
  • Endothelial Growth Factors / blood
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy
  • Hypertension / blood*
  • Hypertension / complications
  • Hypertension / drug therapy
  • Hypertension / physiopathology
  • Intercellular Signaling Peptides and Proteins / blood
  • Lymphokines / blood
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / physiopathology*
  • Risk Factors
  • Thrombophilia / complications
  • Thrombophilia / physiopathology*
  • Thromboplastin / analysis
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Vasodilation
  • von Willebrand Factor / analysis

Substances

  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • von Willebrand Factor
  • Thromboplastin