Arterial stiffness and stroke in hypertension: therapeutic implications for stroke prevention.

Stroke is the second leading cause of mortality worldwide, and the leading cause of death in China and Japan. Its prevention represents a major goal. Identification of primary stroke risk, particularly through newly individualised risk factors including biomarkers of large artery damage such as arterial stiffening, is necessary for determining the appropriate level of intervention. The purpose of this review is to focus on the pathophysiology of arterial stiffness, its predictive value for stroke and the therapeutic implications of this risk factor for stroke prevention. The predictive value of arterial stiffness for stroke was demonstrated in a longitudinal study that included 1715 patients with essential hypertension and measurements of carotid-femoral pulse wave velocity (PWV) [an indicator of arterial stiffness] at entry. Over a mean follow-up period of 7.9 years, during which 25 fatal strokes occurred, PWV significantly predicted stroke (relative risk = 1.39 [(95% CI 1.08, 1.72]; p = 0.02 for each 4 m/sec increase) independently of classical cardiovascular risk factors, including age, cholesterol level, diabetes mellitus, smoking and mean blood pressure. Additional longitudinal studies are needed to confirm the predictive value of aortic stiffness on primary and secondary events, in low- and high-risk populations, in various countries, and using different methodologies of arterial stiffness measurement. Drug treatment could prevent stroke through a reduction in arterial stiffness in parallel with correction of cardiovascular risk factors such as hypertension, dyslipidaemia, diabetes mellitus and smoking, all of which are associated with arterial stiffening. In view of the important local actions of angiotensin II on arterial stiffening, drugs interfering with the renin-angiotensin-aldosterone system should be particularly effective. Promising therapeutic strategies to reduce arterial stiffness include taking advantage of the non-lipid-lowering effects of statins and directly targeting the molecular events leading to arterial stiffening, such as formation of advanced glycation end products.