Visit-to-Visit Blood Pressure Variability

One of the most interesting findings of hypertension research in the past 10 years has been that the cardiovascular protective effects of antihypertensive drugs depend not only on the mean blood pressure (BP) values achieved during treatment but also on the consistency of BP control between on-treatment visits. This was suggested in 2007 by the observation that in patients with hypertension and coronary disease, the protective effect of antihypertensive drugs increased because the percentage of on-treatment visits in which BP was reduced to <140/90 mm Hg increased, even when data were adjusted for the average BP achieved throughout the treatment period. It was documented on a more precise numeric basis in 2010 by the observation that, in hypertensive patients at high cardiovascular risk, the risk of stroke and, to a lesser extent, coronary events increased because visit-to-visit BP variability increased. Similar findings have since been obtained in studies on patients with diabetes mellitus, chronic renal damage, and other diseases, which have also shown that visit-to-visit BP variability may impact not only on major cardiovascular events but also on other types of outcomes, including alterations of renal function and cognitive decline. Although few discordant data have also been reported, this has led to the currently accepted concept that, to maximize cardiovascular protection, BP control needs to be as much as possible steady over time. This implies that physicians should not consider absence of BP control at single visits as of marginal clinical importance (and thus indulge in therapeutic inertia) because this may reduce patients’ chance of survival free of diseases. The studies that have addressed visit-to-visit BP variability are unfortunately also characterized by limitations. One, this phenomenon has to date only be analyzed post hoc, which means that data have been derived from nonrandomized group comparisons, with thus the possibility for the results to be determined by baseline between-group differences, rather than to on-treatment differences of visit-to-visit BP variability. Two, visit-to-visit BP variability has commonly been assessed by the SD or other measures that are not entirely independent on mean BP values, whose contribution to the results can thus not be unequivocally excluded. This has led to the effort to modify the SD until a value unrelated to the mean is found, an empirically based procedure that is not devoid of inconveniencies and criticism. Finally, an important limitation has always been regarded to be the paucity of information on the mechanisms leading to visit-to-visit BP variations. The hypothesis has been advanced that, as for 24-hour or short-term BP variability, these variations are accounted for by spontaneous (and thus largely erratic) modifications of the factors influencing regional circulations and BP values, such as arterial distensibility, sympathetic tone, release of vasoactive substances, myogenic reactivity, baroreflex sensitivity, etc. Modifications of the alerting response to the physician’s or nurse’s visit may also be involved, however, together with more trivial factors such as the greater or lesser temporal distance of the BP measurements from the assumption of antihypertensive drugs at different visits. In the above context, the possibility has progressively gained ground that visit-to-visit BP variability might depend on the greater or lesser adherence of the patient to the treatment regimen because of the growing evidence that adherence to treatment (1) differs markedly among patients with hypertension; (2) shows pronounced time-related variations also within patients; and (3) bears a close relationship with patients’ outcome in both sexes, at all ages and with most, if not all, antihypertensive drug treatments. Expanding previous evidence by the same group, the article published by Kronish et al on this issue of Hypertension provides evidence that adherence to antihypertensive drug treatment is indeed involved in the determination of visit-to-visit BP variability. The authors made use of the data collected in the hypertensive patients of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) to obtain a large group (n=16 878) in which adherence was ≥80% of all prescribed medicaments, and a smaller one (n=2912) in which it was below this figure. During the trial duration, patients showing a lower adherence exhibited a visit-to-visit BP variability that was modestly but significantly greater than that seen in patients with a better adherence (systolic: +8.5%; diastolic: +9.6%; P<0.001 for both). The difference remained significant after multivariable adjustment, although extending the adjustment to the adherence data did not eliminate the observed association between visit-to-visit BP variability and cardiovascular outcomes. This led the authors to also conclude that visit-to-visit BP variations owe their adverse prognostic significance not only to the varying level of adherence to treatment but also to other factors. The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the University of Milano Bicocca and IRCCS Istituto Auxologico Italiano, Milan, Italy. This article was sent to Takayoshi Ohkubo, Guest Editor, for review by expert referees, editorial decision, and final disposition. Correspondence to Professor Giuseppe Mancia, Piazza dei Daini, 4, 20126 Milano, Italy. E-mail [email protected] Visit-to-Visit Blood Pressure Variability An Insight Into the Mechanisms