Prognostic Relevance of Blood Pressure Variability
2013; Lippincott Williams & Wilkins; Volume: 62; Issue: 4 Linguagem: Inglês
10.1161/hypertensionaha.113.01801
ISSN1524-4563
AutoresGianfranco Parati, Xiaoqiu Liu, Juan Eugenio Ochoa, Grzegorz Bilo,
Tópico(s)Hemodynamic Monitoring and Therapy
ResumoHomeHypertensionVol. 62, No. 4Prognostic Relevance of Blood Pressure Variability Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBPrognostic Relevance of Blood Pressure VariabilityRole of Long-Term and Very Long–Term Blood Pressure Changes Gianfranco Parati, Xiaoqiu Liu, Juan Eugenio Ochoa and Grzegorz Bilo Gianfranco ParatiGianfranco Parati Departments of Health Sciences, University of Milano-Bicocca, Milano, Italy (G.P., X.L., J.E.O.); and Department of Cardiology, S.Luca Hospital, IRCCS Istituto Auxologico Italiano (G.P., X.L., J.E.O., G.B.), University of Milano-Bicocca, Milano, Italy. , Xiaoqiu LiuXiaoqiu Liu Departments of Health Sciences, University of Milano-Bicocca, Milano, Italy (G.P., X.L., J.E.O.); and Department of Cardiology, S.Luca Hospital, IRCCS Istituto Auxologico Italiano (G.P., X.L., J.E.O., G.B.), University of Milano-Bicocca, Milano, Italy. , Juan Eugenio OchoaJuan Eugenio Ochoa Departments of Health Sciences, University of Milano-Bicocca, Milano, Italy (G.P., X.L., J.E.O.); and Department of Cardiology, S.Luca Hospital, IRCCS Istituto Auxologico Italiano (G.P., X.L., J.E.O., G.B.), University of Milano-Bicocca, Milano, Italy. and Grzegorz BiloGrzegorz Bilo Departments of Health Sciences, University of Milano-Bicocca, Milano, Italy (G.P., X.L., J.E.O.); and Department of Cardiology, S.Luca Hospital, IRCCS Istituto Auxologico Italiano (G.P., X.L., J.E.O., G.B.), University of Milano-Bicocca, Milano, Italy. Originally published19 Aug 2013https://doi.org/10.1161/HYPERTENSIONAHA.113.01801Hypertension. 2013;62:682–684Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2013: Previous Version 1 See related article, pp 698–705Blood pressure (BP) is characterized by marked fluctuations occurring over different time windows (ie, beat to beat [very short term], within 24 hours [short term], day by day [midterm], between visits spaced by weeks or months, and between seasons, years, and even decades [long term]).1 Normally, short-term BP fluctuations represent an adaptive response of humoral and neural mechanisms to environmental, behavioral, and emotional stimuli. However, experimental and clinical studies have shown that increased short-term BP variability (BPV) may also reflect alterations in cardiovascular regulatory mechanisms, including enhanced sympathetic drive and impaired baroreflex function.Several studies have suggested that long-term BPV is only weakly correlated with short-term BP fluctuations and may thus have different determinants,1,2 including (1) behavioral factors (as suggested by marked changes observed in ambulatory BP levels between workdays and weekends)3; (2) inconsistent BP control by treatment (mainly related to poor treatment adherence and compliance by the patient, as well as improper dosing and titration of antihypertensive treatment); (3) errors in BP measurement, which may significantly influence BPVs from visit to visit1; and (4) seasonal changes in climate-related variables, that is, ambient temperature and daylight hours, which may also exert an important influence on long-term BPV as indicated by the changes occurring in BP levels between summer and winter.4,5During the past decades, several studies have shown that increasing values of BPV (either in the short or in the long term) are associated with hypertensive organ damage6 and an increased cardiovascular risk, independently of average BP values and other major confounders7,8 (Figure). When focusing on the prognostic role of long-term BPV, post hoc analyses of interventional trials in hypertension have shown that increasing values of intraindividual visit-to-visit BPV are strong predictors of cardiovascular morbidity, in some instances superior to average BP values.8 It has been thus suggested that cardiovascular protection by antihypertensive treatment could be potentiated if therapy is targeted not only at achieving control of the average BP values but also at stabilizing BPV in the long term, by reducing BP fluctuations between clinic visits. This could be obtained by adequate dosing and titration of antihypertensive treatment and by improving patient adherence to prescribed drugs.Download figureDownload PowerPointFigure. Different types of blood pressure (BP) variability (BPV), their determinants, and prognostic relevance. *Distinction between long-term (<5 years) and very long–term (≥5 years) BPV as proposed by Hastie et al.10 †Cardiac, vascular, and renal SOD; ‡BPV on a beat-by-beat basis has not been routinely measured in population studies. Modified from Parati et al1 with permission. AHT indicates antihypertensive treatment; CV, cardiovascular; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; IHD, ischemic heart disease; MA, microalbuminuria; MI, myocardial infarction; and SOD, subclinical organ damage.Several limitations of the studies exploring the prognositc relevance of long-term visit-to-visit BPV should be considered, however. (1) The differences in cardiovascular risk levels between the populations included in these studies have significantly influenced the frequency of observed outcomes. Indeed, an increased visit-to-visit BPV was consistently associated with an increased risk of cardiovascular events in high-risk subjects8 but not in subjects at low-to-moderate cardiovascular risk.9 (2) Short follow-up periods and insufficient number of outcomes in some studies prevented the prognostic value of long-term BPV from being conclusively determined, in particular when focusing on specific causes of mortality. (3) Problems related to BP measurement might also have importantly affected BPV estimates. More specifically, use of different techniques for BP measurement (ie, office-based, ambulatory, or home-based BP monitoring) and the variable number of BP readings considered, together with different time intervals between measurements, are all likely to have played a significant role. (4) Use of different indices of BPV in different studies, that is SD, coefficient of variation, average real variability, and variance independent of mean, may also have affected the interpretation and generalization of results. (5) Moreover, some studies assessed interindividual BPV, that is visit-to-visit BP variations among patients, rather than intraindividual BPV, that is visit-to-visit BP variations within subjects, and interindividual BPV might not accurately reflect changes in BP between visits in individual subjects. (6) Finally, not all studies have properly dealt with the collinearity between average BP levels and BPV, in spite of the fact that BPV is known to increase proportionally with the average BP levels.Against this background, the article by Hastie et al10 published in the current issue of Hypertension provides relevant information on the prognostic role of long-term BPV. This study has explored the relationship between intraindividual visit-to-visit BPV and mortality in a large population of 16 011 treated hypertensive patients, in whom BPV was assessed over up to 9 years and who were followed up for events over a period extending up to 35 years. Remarkably, long-term visit-to-visit BPV was assessed not only within the first year (Y1) and between the years from 2 to 5 (Y2–5), but also within larger time frames (ultra–long-term BPV; ie, from years 1 to 5, from years 5 to 10 [Y5–10], and over a time window up to 9 years of follow-up [ie, from years 2 to 10]). The main result of this study is the finding of a consistent association between increasing values of long- and ultra long–term BPV (assessed through calculation of average real variability, coefficient of variation, and SD) and risks of all-cause, cardiovascular, and noncardiovascular mortality. These associations remained significant even after adjustment for average BP levels and across different strata of average systolic BP. Even in subjects with controlled systolic BP, there was a linear increase in mortality with increasing long-term BPV. However, in contrast with previous studies and despite the large sample size in the study of Hastie et al,10 no association was found between BPV and stroke mortality.Another interesting result of this study is the finding of significantly higher values of BPV during the first year of follow-up, compared with those in subsequent follow-up periods. This finding has 2 plausible (and not mutually exclusive) explanations. One, it could reflect the instability in BP control during the starting phase of antihypertensive therapy because of the frequent changes in antihypertensive treatment regimen needed to achieve optimal BP control in this period. This may support the concept that drug titration may contribute to BP instability, reflected by long-term BPV estimates. Two, variability estimates could be higher and less stable during the first year because of the lower average number of BP values considered to compute BPV, compared with the other time periods (ie, 3.6 and 7.8 BP values, for BPV computed in the first year and for years 2–5, respectively).Although Hastie et al10 provide consistent evidence on the prognostic relevance of visit-to-visit BPV, thus supporting its assessment and management in clinical practice, a limitation of their study is the quantification of BPV based on office-based BP (OBP) measurements only. Although OBP measurement is the most commonly used method to assess BP control and visit-to-visit BPV in clinical practice, it is also an acknowledged imperfect indicator of actual BP control. Thus, it may not necessarily provide an accurate estimate of visit-to-visit BPV in treated patients because of factors such as observer's bias or alarm reaction during the medical visit (white coat effect). Moreover, it cannot provide information on BP levels during subjects' usual activities and can only be obtained during a limited number of visits. As a result of all these limitations, OBP measurement is often unable to offer a representative evaluation of patients' actual BP burden. Thus, a more proper assessment of intraindividual visit-to-visit variability during the long-term follow-up of treated hypertensives could be achieved by combining OBP readings with out-of-office BP-measuring techniques (ambulatory or home-based BP monitoring), which are known to provide a more reliable assessment of the degree of BP control than repeated OBP measurements. In particular, repeated assessment of home BP values, averaged over 1 week before each doctor's visit, may offer a solid base to assess BPV in a long-term follow-up, while allowing to assess the consistency in BP control over time.11 Moreover, repeated ambulatory BP-monitoring sessions might allow the accurate quantification of visit-to-visit BPV, although this approach is less feasible because of limited availability of this diagnostic tool and because of poor patients' acceptance in case of its repeated performance.Another aspect of the study by Hastie et al10 that deserves to be mentioned is the poor correlation between BPV estimates obtained at different time frames (intraclass correlation coefficients always <0.32). Although the authors ascribed this finding to a potential failure in achieving a similar degree of stability in BP control over the different time windows considered, it might also be because of the technical interference by varying numbers of visits and intervisit intervals.In conclusion, the study by Hastie et al10 corroborates the existing evidence that increased BPV between clinic visits has a significant prognostic value also in the long run. This might reflect the burden imposed by intermittent surges in BP levels to the cardiovascular system over the years. The demonstration that ultra long–term BPV recorded over up to 9 years is also a strong predictor of mortality in treated hypertensives further emphasizes the importance of not only achieving but also maintaining stable BP control in the long term. Identification of optimal therapeutic strategies able to stabilize visit-to-visit BPV and assessment of the impact of such stabilization on outcome require further studies, ideally implementing both OBP and out-of-office BP-monitoring techniques for their adequate evaluation.DisclosuresNone.FootnotesThe opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.Correspondence to Gianfranco Parati, Department of Cardiology, S.Luca Hospital, Istituto Auxologico Italiano, University of Milan-Bicocca, Piazza Brescia 20, Milano 20149, Italy. E-mail [email protected]References1. Parati G, Ochoa JE, Lombardi C, Bilo G. Assessment and management of blood-pressure variability.Nat Rev Cardiol. 2013; 10:143–155.CrossrefMedlineGoogle Scholar2. Mancia G, Facchetti R, Parati G, Zanchetti A. 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Rodionov A (2020) High Blood Pressure Variability is an Additional Cardiovascular Risk Factor, Rational Pharmacotherapy in Cardiology, 10.20996/1819-6446-2020-02-02, 16:1, (94-98) See C, Tseng C, Lin W, Chao J, Kuo T and Wang M (2021) Seasonal Change in Home Blood Pressure Monitoring Is Associated With Renal Outcome and Mortality in Patients With Chronic Kidney Disease, Frontiers in Medicine, 10.3389/fmed.2021.672651, 8 Rodionov A (2017) Hypertensive urgency or high blood pressure variability?, Terapevticheskii arkhiv, 10.17116/terarkh2017893108-111, 89:3, (108-111) October 2013Vol 62, Issue 4 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.113.01801PMID: 23959550 Originally publishedAugust 19, 2013 PDF download Advertisement SubjectsHypertension
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