Pulse pressure and antihypertensive agents.

Pulse Pressure and Antihypertensive Agents To the Editor: In their subanalysis of the LIFE study,1 the authors conclude that they “show superior protection against stroke in patients treated with losartan when compared with atenolol . . . This difference may be related to specific effects of angiotensin type 1 receptor antagonism . . . beyond blood BP reduction.” The authors do not consider the alternative hypothesis: that the changes in pulse pressure (PP) might differ markedly under losartan and atenolol and also according to the site of PP arterial measurements.2 As a consequence of differences in arterial stiffness and timing of wave reflections along the arterial tree, PP is lower in central than in peripheral arteries, whereas mean arterial pressure (MAP) is nearly the same. This phenomenon is attenuated in aged people and in the presence of bradycardia.2 Thus, mechanical forces at the site of target organ damage are not accurately measured by the brachial BP cuff. Furthermore, antihypertensive agents may cause the same MAP reduction at the brachial and central arteries sites but with different values of central PP.2–5 For instance, in double-blind studies comparing converting enzyme inhibitors and -blockers, atenolol does not modify carotid or aortic PP, whereas converting enzyme inhibitors markedly reduce carotid PP for the same MAP reduction.4,5 In the present study, brachial PP is a predictor of stroke when measured in baseline conditions, mostly in the higher PP tertile of the population, in which mean age is 69 years. Under drug treatment by atenolol, it is expected that central PP remains unchanged, whereas under losartan, central PP is expected to be reduced. Thus, the role of local mechanical forces such as PP should have to be raised in the mechanism of stroke prevention. Therapeutic trials have shown that the brain is the location where the role of mechanical factors is of major importance for the reduction of CV events.