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Abstract

Aims

Sleep-time blood pressure (BP) is a stronger risk factor for cardiovascular disease (CVD) events than awake and 24 h BP means, but the potential role of asleep BP as therapeutic target for diminishing CVD risk is uncertain. We investigated whether CVD risk reduction is most associated with progressive decrease of either office or ambulatory awake or asleep BP mean.

Methods and results

We prospectively evaluated 18 078 individuals with baseline ambulatory BP ranging from normotension to hypertension. At inclusion and at scheduled visits (mainly annually) during follow-up, ambulatory BP was measured for 48 consecutive hours. During the 5.1-year median follow-up, 2311 individuals had events, including 1209 experiencing the primary outcome (composite of CVD death, myocardial infarction, coronary revascularization, heart failure, and stroke). The asleep systolic blood pressure (SBP) mean was the most significant BP-derived risk factor for the primary outcome [hazard ratio 1.29 (95% CI) 1.22–1.35 per SD elevation, P < 0.001], regardless of office [1.03 (0.97–1.09), P = 0.32], and awake SBP [1.02 (0.94–1.10), P = 0.68]. Most important, the progressive attenuation of asleep SBP was the most significant marker of event-free survival [0.75 (95% CI 0.69–0.82) per SD decrease, P < 0.001], regardless of changes in office [1.07 (0.97–1.17), P = 0.18], or awake SBP mean [0.96 (0.85–1.08), P = 0.47] during follow-up.

Conclusion

Asleep SBP is the most significant BP-derived risk factor for CVD events. Furthermore, treatment-induced decrease of asleep, but not awake SBP, a novel hypertension therapeutic target requiring periodic patient evaluation by ambulatory monitoring, is associated with significantly lower risk for CVD morbidity and mortality.

Asleep blood pressure , Ambulatory blood pressure monitoring , Bedtime hypertension chronotherapy , Cardiovascular risk , Stroke
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: [email protected].
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
Topic:
Issue Section:
Clinical Research > Hypertension
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Comments (1)
Ambulatory blood pressure and mortality.
29 September 2018
José R. Banegas, Luis M. Ruilope, Alejandro de la Sierra, Ernest Vinyoles, Manuel Gorostidi, Juan J. de la Cruz, Gema Ruiz-Hurtado, Julian Segura, Fernando Rodríguez-Artalejo, Bryan Williams
Universidad Autónoma de Madrid, University of Barcelona, Spain, and University College London, UK
Dear Editor, in a recent article in the Journal,1 Hermida and cols. made two criticisms concerning some results of our previous report on the association between ambulatory blood pressure and mortality.2 First, they commented that the hazard ratios for mortality due to some specific cardiovascular diseases associated with awake systolic blood pressure did not match with the hazard ratio for mortality due to all cardiovascular diseases. Hermida and cols are correct and, actually, hazard ratios for daytime systolic blood pressure in our study are 1.56 and 1.57 for ischemic heart disease and stroke mortality, respectively, instead of 1.025. This was due to an error in the calculation of these two single hazard ratios, and the corresponding correction has been made in the published material. Thus, hazard ratios of mortality for all cardiovascular diseases together and for those specific cardiovascular diseases were very similar. This correction does not alter the conclusions of our paper that ambulatory blood pressure was better than clinic blood pressure in predicting all-cause and cardiovascular mortality,2 a result consistent with Hermida and cols´ findings.1

Second, these authors were surprised that, in our study, hazard ratios of clinic and ambulatory systolic pressures were very similar for all-cause and for cardiovascular mortality (some were apparently identical because of rounding-off). This is consistent with some other previous reports. For example, in the International Database on Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes (IDACO), hazard ratios for 1-SD increment in nighttime systolic blood pressure were practically identical for total mortality (1.22), cardiovascular mortality (1.22), and non-cardiovascular mortality (1.21).3 Some non-cardiovascular causes of death, including cancer, respiratory, digestive, renal, and ill-defined causes (a considerable part of them are presumably related to vascular disease) have also been found associated with blood pressure.4-6 In our study, hazard ratios of mortality per 1SD increase in clinic and 24-hour systolic pressures were: for cancer 1.1 and 1.3, respectively; for endocrine, nutritional and metabolic diseases, 1.0 and 1.3; for mental and behaviour diseases, 0.8 and 1.3; for nervous system and sense organs diseases, 0.8 and 1.2; for respiratory system, 0.9 and 1.3; for digestive system diseases, 1.2 and 1.3; and for genital-urinary diseases, 0.9 and 1.5. Many of these associations were not statistically significant for clinic pressure but were significant for ambulatory pressure. Overall, when deaths from unknown, ill-defined and non-classified causes were not included, the hazard ratios for total mortality associated with 1-SD increase in clinic and 24-hour systolic pressure were 1.01 and 1.35, respectively and, as expected, were lower than those for cardiovascular mortality (1.02 and 1.58, respectively). Overall, the results show consistently the superiority of ambulatory over clinic pressure.

References
1.- Hermida RC, Crespo JJ, Otero A, Domínguez-Sardiña M, Moyá A, Ríos MT, Castiñeira MC, Callejas PA, Pousa L, Sineiro E, Salgado JL, Durán C, Sánchez JJ, Fernández JR, Mojón A, Ayala DE; Hygia Project Investigators. Asleep blood pressure: significant prognostic marker of vascular risk and therapeutic target for prevention. Eur Heart J. 2018 Aug 10. doi: 10.1093/eurheartj/ehy475.

2.- Banegas JR, Ruilope LM, de la Sierra A, Vinyoles E, Gorostidi M, de la Cruz JJ, Ruiz-Hurtado G, Segura J, Rodríguez-Artalejo F, Williams B. Relationship between clinic and ambulatory blood-pressure measurements and mortality. N Engl J Med. 2018;378:1509–1520.

3.- Boggia J, Li Y, Thijs L, Hansen TW, Kikuya M, Björklund-Bodegård K, Richart T, Ohkubo T, Kuznetsova T, Torp-Pedersen C, Lind L, Ibsen H, Imai Y, Wang J, Sandoya E, O'Brien E, Staessen JA; International Database on Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes (IDACO) investigators. Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study. Lancet. 2007;370:1219-1229.

4.- Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903-1913.

5.- Stocks T, Van Hemelrijck M, Manjer J, Bjørge T, Ulmer H, Hallmans G, Lindkvist B, Selmer R, Nagel G, Tretli S, Concin H, Engeland A, Jonsson H, Stattin P. Blood pressure and risk of cancer incidence and mortality in the Metabolic Syndrome and Cancer Project. Hypertension. 2012;59:802-810.

6.- Schnabel E, Karrasch S, Schulz H, Gläser S, Meisinger C, Heier M, Peters A, Wichmann HE, Behr J, Huber RM, Heinrich J; Cooperative Health Research in the Region of Augsburg (KORA) Study Group. High blood pressure, antihypertensive medication and lung function in a general adult population. Respir Res. 2011;12:50.

The authors declare no competing financial interests.
Submitted on 29/09/2018 10:33 AM GMT