clinicaltrials.gov Identifier: NCT01763866.

Background-Elevated pulse pressure (PP) is associated with increased cardiovascular risk and is thought to be secondary to elastin fragmentation with secondary collagen deposition and stiffening of the aortic wall, leading to a dilated, noncompliant vasculature. Methods and Results-By use of calibrated tonometry and pulsed Doppler, arterial stiffness and pulsatile hemodynamics were assessed in 128 subjects with uncomplicated systolic hypertension (supine systolic pressure Ն140 mm Hg off medication) and 30 normotensive control subjects of comparable age and gender. Pulse-wave velocity was assessed from tonometry and body surface measurements. Characteristic impedance (Z c ) was calculated from the ratio of change in carotid pressure and aortic flow in early systole. Effective aortic diameter was assessed by use of the water hammer equation. Hypertensives were heavier (PϽ0.001) and had higher PP (PϽ0.001), which was attributable primarily to higher Z c (PϽ0.001), especially in women. Pulse-wave velocity was higher in hypertensives (Pϭ0.001); however, this difference was not significant after adjustment for differences in mean arterial pressure (MAP) (PϾ0.153), whereas increased Z c remained highly significant (PϽ0.001). Increased Z c in women and in hypertensive men was attributable to decreased effective aortic diameter, with no difference in wall stiffness at comparable MAP and body weight. Conclusions-Elevated PP in systolic hypertension was independent of MAP and was attributable primarily to elevated Z c and reduced effective diameter of the proximal aorta. These findings are not consistent with the hypothesis of secondary aortic degeneration, dilation, and wall stiffening but rather suggest that aortic function may play an active role in the pathophysiology of systolic hypertension.

losartan, valsartan, and irbesartan (8.2, 7.9, and 9.9 mm Hg, respectivelyA ngiotensin II receptor blockers (ARBs) are the newest class of approved antihypertensive agents and the second class of drugs to exert their primary antihypertensive action by interrupting the renin-angiotensin system. ARBs prevent the hypertensive effects of angiotensin II by selective blockade of the angiotensin II type 1 (AT 1 ) receptor. 1 The success of ARBs in the treatment of hypertension is reflected in the fact that six of these agents have been approved for this use since 1994.Olmesartan medoxomil is a new ARB that was discovered during a systematic survey of the AT 1 binding actions of substituted imidazole-5-carboxylic acids. 2 It is a prodrug that, following oral administration, is rapidly and completely de-esterified in the gut to its active form, in a reaction that is not cytochrome P-450-dependent. 3 This active metabolite, olmesartan, is a potent and selective AT 1 receptor antagonist, with no agonist activity. 3