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Cerebral consequences of hypertension: where do they lead?
1Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, London, Ontario, Canada.
Insights
Treating high blood pressure effectively prevents arteriolar events but not atherosclerotic strokes, suggesting hypertension has dual mechanisms. Mental stress emerges as a significant predictor of atherosclerosis progression, independent of traditional risk factors.
Area of Science:
- Cardiovascular Medicine
- Hypertension Research
- Vascular Biology
Background:
- Hypertension is a primary risk factor for both atherosclerosis complications (myocardial/cerebral infarction) and small vessel disease complications (renal failure, intracerebral hemorrhage).
- If blood pressure elevation were the sole cause, blood pressure-lowering treatments should equally prevent all hypertension-related vascular issues.
Purpose of the Study:
- To investigate the differential effects of hypertension treatment on arteriolar versus atherosclerotic vascular events.
- To explore the hypothesis that hypertension involves both pressure (fluid energy) and kinetic energy components, influencing arterial remodeling.
- To identify novel predictors of atherosclerosis progression, particularly the role of mental stress.
Main Methods:
- Utilized data from a large study initiated after the installation of a computed tomography (CT) scanner, which increased hypertension detection and treatment.
- Examined the impact of antihypertensive drugs on arterial flow disturbances and the relationship between mental stress and atherosclerosis progression.
- Developed a regression model to assess the effect of stress responses on atherosclerosis and introduced a new trait: 'unexplained atherosclerosis progression'.
Main Results:
- Treatment of high blood pressure successfully prevented arteriolar strokes but did not prevent atherosclerotic strokes.
- The rise in blood pressure during mental stress was a more potent predictor of atherosclerosis progression than established risk factors like age, sex, blood pressure, smoking, lipids, or diabetes.
- A new quantitative trait, 'unexplained atherosclerosis progression,' was identified.
Conclusions:
- Hypertension's vascular consequences may stem from distinct mechanisms, one related to pressure and another to kinetic energy and disturbed flow patterns.
- Mental stress is a critical, independent predictor of atherosclerosis progression, highlighting its role in cardiovascular disease.
- The concept of 'unexplained atherosclerosis progression' offers a new avenue for discovering genes involved in atherosclerosis and managing its genetic heterogeneity.
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.