Visit-to-visit blood pressure variability: added ‘VALUE’ as a risk marker in low- and high-risk patients

The growing interest in the variability of blood pressure is related to the repeated demonstration of its independent predictive value for organ damage and cardiovascular events. In particular, visit-to-visit blood pressure variability has gained attention from physicians since large blood pressure fluctuations from one visit to another are common observations in clinical practice, and have been related to high risk of cardiovascular complications. Several indices are available for the quantification of visit-to-visit blood pressure variability, such as standard deviation and coefficient of variation. Visit-to-visit blood pressure variability can be influenced by a number of factors, including the length of follow-up, number of measures, changes in blood pressure measurement procedures, antihypertensive drugs, patient drug adherence, and environmental conditions including seasonal changes. It is also likely to be influenced by intrinsic characteristics of the patient, among them increased arterial stiffness and/or altered baroreflex function that impairs the buffering of blood pressure changes. Visit-to-visit blood pressure variability can damage target organs, either directly in response to the mechanical effect of blood pressure variations or indirectly in association with the mechanisms at the origin of abnormal cardiovascular regulatory mechanisms leading to higher visit-to-visit blood pressure variability. Post hoc analyses of large randomized clinical trials have been performed since both office blood pressure values at repeated visits and outcomes were available. A consistent finding was that increased visit-to-visit blood pressure variability was predictive of fatal and nonfatal cardiovascular events independently of mean blood pressure. Not surprisingly, the higher the cardiovascular risk at baseline, the higher the predictive value of visit-to-visit blood pressure variability for cardiovascular events. Although the translation of these findings into clinical practice is obvious for high-risk patients, their clinical applicability remains limited in younger patients and those with a lower mean blood pressure. Indeed, these patients are generally considered as at low-risk, a statement that can revisited if visit-to-visit blood pressure variability is available. The article by Mehlum et al. published in this issue of the European Heart Journal provides an important contribution with regard to the issue of the predictive value of visit-to-visit variability in blood pressure for cardiovascular events. The authors analyzed the data of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, a multinational randomized-controlled, double-masked trial of valsartan vs amlodipine, in 15 245 patients with hypertension and at least one additional risk factor for cardiovascular event, with a mean duration of follow-up of 4.0 years. They selected 13 803 patients who had no event during the first 6 months and had at least three visits. Visit-to-visit blood pressure variability was assessed by the standard deviation of at least three mean systolic blood pressures, each calculated from three measurements during the visit. An important finding is that patients in the highest quintile of visit-to-visit blood pressure variability had a twoto threefold higher risk of cardiovascular event than those in the lowest quintile, (ischaemic stroke, myocardial infarction, and congestive heart failure). These results were adjusted for a large number of variables, including mean systolic blood pressure during treatment. In that respect, the authors confirm and extend the findings of previous large randomized clinical trials, such as the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA) and the Losartan Intervention For Endpoint reduction in hypertension (LIFE) studies, i.e. increased visit-to-visit blood pressure variability was predictive of fatal and nonfatal cardiovascular events independently of mean blood pressure. The findings of Mehlum et al. are also stimulating because associations between visit-to-visit blood pressure variability and cardiovascular events were stronger among the younger patients (i.e. aged 50–67 years) and patients with lower systolic blood pressure (i.e. <137.8