How to study the role of hypertension in atherosclerosis. Lessons from MIDAS. Multicentre Isradipine Diuretic Atherosclerosis Study.

The development of atherosclerosis is clearly linked to the level of blood pressure. This is illustrated by the difference of atheroma formation in arteries as compared to veins, the development of atherosclerosis in veins transplanted to the arterial circulation or the finding of atherosclerosis also in the pulmonary circulation as an effect of pulmonary hypertension. Several experimental studies have also illuminated the strong link between high blood pressure and the development of atherosclerosis. From a therapeutic point of view it is worth noting that the lowering of blood pressure per se has a positive effect on the development of atherosclerosis. In particular, calcium antagonists have been shown, in numerous experimental studies, to have an antiatherosclerotic effect. The positive results in animal studies led to studies in man, the first of which was the MIDAS Study. The Multicentre Isradipine Diuretic Atherosclerosis (MIDAS) Study was a comparison between the dihydropyridine-derived calcium antagonist isradipine and hydrochlorothiazide in 883 hypertensive patients. B-mode ultrasonography of the carotid artery was used in order to evaluate changes in wall thickness and the development of atherosclerotic plaques during a 3-year period. The final publication has yet to appear in a medical journal. However, the study and its main findings have been presented at several international scientific meetings. In brief, isradipine was significantly more effective than hydrochlorothiazide in preventing an increase in intima-media thickness at several points of measurement in the carotid artery in spite of the fact that systolic blood pressure was not lowered as effectively by isradipine as by the diuretic therapy. There are numerous lessons to be learnt from MIDAS for future studies of this kind. A good example of this is the European Lacidipine Study of Atherosclerosis (ELSA) which is currently in progress in several European countries. By careful analysis of MIDAS an improved study design has been created, which should result in a definitive and irrefutable answer to the issue of the clinical importance of calcium antagonist treatment in the prevention of atherosclerosis.