Cerebral consequences of hypertension: where do they lead?

BACKGROUND: Hypertension is a major risk factor for two distinct kinds of vascular problems: complications of atherosclerosis including myocardial and cerebral infarction, as well as complications of hypertensive small vessel disease, including renal failure, intracerebral hemorrhage and lacunar infarctions. If these consequences were solely due to elevation of blood pressure, they should be equally prevented by treatments that reduce blood pressure. OBSERVATION: The installation of a computed tomography (CT) scanner in our hospital before the initiation of a large study by the Department of Family Medicine markedly increased the detection and treatment of hypertension in our region. As a result, we found that treating high blood pressure prevented arteriolar but not atherosclerotic strokes. HYPOTHESIS: Our observation raises questions about the nature of hypertension, which can be regarded as a disorder of fluid energy, with arteriolar consequences being due to elevated pressure, and atherosclerotic consequences being related to kinetic energy, derived from pressure energy when flow patterns become disturbed. It is hypothesized that the remodelling of arteries to conform to flow patterns may be driven by increased nitric oxide at regions of high shear, leading the artery to 'grow away' from high shear, whereas endothelin released in regions of low shear may cause the artery to 'fill in' the low shear region. This may, in part, explain the protection that women enjoy until menopause, as estrogen increases nitric oxide release and probably reduces endothelin production in the endothelium. PREDICTORS OF ATHEROSCLEROSIS PROGRESSION: The pressure kinetic construct has led to studies on the effects of antihypertensive drugs on flow disturbances in arteries leading, in turn, to studies on the relationship between mental stress and atherosclerosis. We have shown that the rise in blood pressure during mental stress is a stronger predictor of atherosclerosis progression than any of the standard risk factors such as age, sex, blood pressure, smoking, lipids or diabetes. The regression model used to make explicit the effect of stress responses on atherosclerosis not only offers a powerful new way to identify new causes of atherosclerosis, but also leads to a new quantitative trait, the rate of progression of atherosclerosis not explained by the Framingham risk factors. This trait, "unexplained atherosclerosis progression', in combination with three-dimensional ultrasound measurement of atherosclerosis, may lead to the discovery of new genes for atherosclerosis and thus help to manage the genetic heterogeneity of this disease.