Office blood pressure (BP) is considered the gold standard to estimate the risk accompanying an elevation in BP. In daily clinical practice, iterative determinations of office BP constitute the method to consider whether the control of BP is adequate, and frequently the value obtained in an isolated visit is used to modify the treatment of the patient without paying due attention to the values of BP obtained in previous visits. According to the new guidelines of the European Society of Hypertension and the European Society of Cardiology, adequate control is considered when office BP is <140/90 mm Hg for practically the whole population with hypertension. Values above this value have been typically considered as uncontrolled but without any reference to differences among visits. It is well known that BP is characterized by marked short-term fluctuations occurring within a 24-hour period. These short-term variations have been shown to be the result of complex interactions between extrinsic environmental and behavioral factors and intrinsic cardiovascular regulatory mechanism. Short-term BP variability has been analyzed using ambulatory BP monitoring and has been shown to increase with the development, progression, and severity of cardiac, vascular, and renal damage. Recently, the concept of visit-to-visit variability (VVV) obtained through the analysis of systolic BP (SBP) in the repetitive visits in a well-known trial, the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), allowed Rothwell and colleagues to conclude in their post-hoc analysis that VVV in SBP and maximum SBP are strong predictors of stroke, independent of mean SBP. It is well established that adverse cardiovascular consequences of hypertension largely depend on absolute BP values and the concept of BP variability along the different visits to the doctor's office has added a new factor to be considered in order to obtain an adequate evaluation of risk and to pharmacologic therapy once this is started and maintained in hypertensive patients. After the initial publication, other groups have come to confirm, in post-hoc analyses, the relevance of VVV for the prediction of cardiovascular events and mortality in hypertensive patients and using data obtained in the general population.[4-6] In the present issue of the Journal, Kostis and colleagues investigated the relevance of VVV during the very long-term follow-up (up to 17 years) of patients initially included in the Systolic Hypertension in the Elderly Program (SHEP). They confirmed that VVV was associated with cardiovascular death after 17 years of follow-up and after adjustment for confounding variables. This study had two other important advantages over previously published data. First, it was a placebo-controlled trial, which allowed the analysis of VVV in the placebo-treated group. Second, the influence of long-term adherence was considered, which allowed the investigation of the influence of this enormously important parameter on VVV. The relationship between VVV and cardiovascular outcome was significantly stronger in the active treatment group compared with the placebo. This could contribute, partly in agreement with previous data published in this Journal, to the hypothesis launched by the authors that inconsistent adherence to active therapy may be causally related to VVV as well as to the occurrence of cardiovascular death. Inconsistent adherence to placebo would be expected to have less influence on BP variability than active therapy. These findings expand the knowledge about the mechanisms underlying the existence of an increased VVV promoted either directly or through coexistent risk factors.[3, 9]
Another interesting aspect of the influence of active medication on VVV consists of its variation with time, with variability being more intense during the first year of follow-up, in which frequent changes in antihypertensive therapy take place and fluctuations in BP can be expected to occur before attaining the adequate amount of treatment required for sustained control of BP. With respect to the medication class effects on VVV, recent data have shown that diuretic therapy, as that used in SHEP, lowers BP variability, albeit the magnitude of the effect of antihypertensive medication class explained <10% of the VVV of BP.
In summary, the data published in the study by Kostis and colleagues come to extend the understanding of VVV in BP, demonstrating that it is more important when active therapy is compared with placebo and introducing inconsistent adherence as a new factor that contributes to the understanding of this phenomenon, which has been shown to be relevant for the prognosis of hypertensive patients.