Clinical Relevance of Day-by-Day Blood Pressure and Heart Rate Variability
New Information From Home Self-Measurements
Both in normotensive and in hypertensive subjects, blood pressure (BP) is characterized by continuous fluctuations in relation to the different daytime and nighttime activities.1 Studies based on ambulatory BP monitoring (ABPM) have provided evidence that BP and heart rate (HR) variability (V) over 24 hours carry important pathophysiological information and have clinical relevance both in the diagnostic and prognostic assessments of hypertension. Different BPV and HRV patterns reflect specific features of autonomic cardiovascular regulation, and the magnitude of BP swings over the day and night has been shown to be associated with severity of organ damage and rate of cardiovascular events.2–5 As a consequence, it has been suggested recently that the benefits of hypertension treatment, in terms of organ damage prevention or regression and in terms of event rate reduction, might be greater by targeting not only mean BP level reduction but also the attenuation of the deranged BP variability found frequently in hypertensive patients.6
Traditional office BP measurements are unable to account for daily life BPV and HRV,1 which explains the growing interest toward out-of-office BP measurements, either through ABPM or, in more recent times, through home (H)BPM. In spite of its relevant advantages, however, routine use of ABPM has found only limited applicability in clinical practice up to now, partly because of its inconvenience in active patients and because of its impact on health care costs. Use of HBPM in the diagnosis and management of arterial hypertension, however, is continuously increasing, its rapid diffusion being favored by technological progress in the design and production of HBPM devices, by their progressively wider availability and lower cost, and by the increasing awareness among doctors and patients of the importance of regular out-of-office BP monitoring, even when ABPM is unavailable. This has led to the very recent and almost simultaneous publication, in the United States and in Europe,7,8 of detailed recommendations aimed at promoting and improving HBPM use in daily practice.
Although HBPM and ABPM share a number of advantages as compared with office BP readings (Table), including better reproducibility and the possibility to identify patients with “white coat hypertension” or “masked hypertension” (BP elevation only in the office and not in daily life, or vice versa, respectively), when these methods are directly compared, important differences can be observed (Table). Indeed, both in the American and in the European guidelines, ABPM and HBPM are clearly proposed as complementary and not as alternative techniques, able to provide important information on BP and HR in different conditions and over different periods. As an example, when both ABPM and HBPM were used in the same subjects to identify masked hypertension, a concordant diagnosis was obtained only in half of the patients, whereas in the remaining ones masked hypertension was identified only by one method but not by the other.8 Similar discrepancies were found in the diagnosis of white coat hypertension. Concerning their prognostic value, average levels of both HBP and ABP are more closely associated with severity of organ damage and rates of events than office BP. However, ABPM may be superior to HBPM when focusing on 24-hour BP and HR profiles, in particular when considering the prognostic value of nocturnal ABP and 24-hour BPV and HRV, whereas HBPM may offer some information only on day-by-day changes in BP and HR, of which the prognostic relevance was never specifically addressed in the past.
The common belief that clinically relevant information on BPV can be obtained from ABPM only is challenged by the results of the study by Kikuya et al,9 published in the present issue of Hypertension. In this study, the authors investigated the prognostic value of day-by-day BPV and HRV in 2455 residents in the town of Ohasama, aged 35 to 96 years, whose home BP and HR were measured once every morning for a median period of 26 days. These subjects were then included in a longitudinal follow-up period with a median duration of 11.9 years, during which a total of 462 deaths occurred (168 cardiovascular and 294 noncardiovascular deaths). The impact of day-by-day BPV and HRV on mortality was assessed through Cox regression analysis, by computing hazard ratios adjusted for patient baseline characteristics. An increase in systolic BPV was associated with significantly increased hazard ratios for cardiovascular and stroke mortality but not for cardiac mortality. An increased HRV was associated with greater cardiovascular and cardiac mortality but not stroke mortality. Similar findings were observed for diastolic BPV. Comparable results were obtained by considering BPV and HRV normalized for the respective mean values and computed as coefficients of variation to account for the possible confounding effect on the prognosis of between-subject differences in mean BP or HR values. The authors’ conclusions are that estimates of day-by-day BPV and HRV from HBPM represent additional useful and simple tools to assess patient cardiovascular risk.
Although these data seem to open new perspectives in assessing the risk related to cardiovascular variability in clinical practice, even without performing 24-hour ABPM, caution is needed in the interpretation of these results because of some study limitations. First, the prognostic value of home BPV and HRV was assessed by taking into consideration 1 morning BP and HR measurement per day only. It is well known, however, that when home BP and HR are repeatedly measured within each measurement session, they show a progressive reduction ongoing from the first to the subsequent readings, which makes the average of several measurements a more reliable index of the actual daily home BP and HR levels than a single reading and may have an impact also on the assessment of day-by-day BPV and HRV.8,10 Second, data in the study by Kikuya et al9 was collected at baseline only over a 4-week period. Thus, the possible impact of time and treatment on home BP and HR mean levels and variability during follow-up could not be accounted for. Third, another important methodologic problem is the possibility of artifacts and errors at the time of self-BP and HR measurements by the patients, given that, in this study, the quality of HBPM was not checked any longer after an initial training. Thus, a possible interference of artifactual measurements with the quantification of day-by-day home BPV and HRV cannot be excluded. Fourth, a puzzling finding of the study by Kikuya et al9 is the association of an increased HRV with a worse outcome. This is in contrast with the available evidence that a reduced rather than an enhanced HRV carries an adverse prognosis.11 No satisfactory explanation for such a finding is offered in this article, although we may speculate that differences in the time constant of HR changes, in the underlying autonomic mechanisms, and in their possible determinants may be involved in explaining the different prognostic impact of increases in day-by-day rather than in beat-by-beat HRV. Finally, the results of this study have been obtained in a Japanese population, predominantly including middle-aged and elderly individuals. Whether a similar prognostic value of day-by-day BPV and HRV can be found also when considering Western populations and a wider age range, should be addressed in future studies.
In conclusion, the evidence provided by Kikuya et al9 supports the suggestion that the quantification of day-by-day BPV and HRV at home adds to the stratification of risk based on the simple assessment of average home BP and HR values. However, before recommending this approach in routine clinical practice, a few issues would need to be further addressed, as acknowledged by the authors themselves. First, the factors responsible for between-subject differences in day-by-day home BPV and HRV are yet to be identified, which prevents any possible countermeasure to be defined. Second, the possible therapeutic implications of an increased day-by-day home BPV and HRV, in terms of drug prescription and dosing, are still totally unexplored. Finally, the prognostic value of differences in home BPV and HRV should be compared in the same subjects with the prognostic value of concomitant differences in office and in ambulatory BPV and HRV to more precisely gauge the specific contribution of day-by-day changes in home BP and HR to cardiovascular risk assessment vis-à-vis the information provided by other BPM techniques.
In spite of these still open problems, the data obtained by Kikuya et al9 should, nevertheless, raise greater attention toward the role of day-by-day changes in home BP and HR in the prognostic stratification of hypertensive patients while waiting for future studies to address this issue in more depth.
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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