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What is the association of office and ambulatory blood pressure with subsequent risk of mortality and cardiovascular outcomes?
In a population-based cohort of 11 135 adults, higher 24-hour and nighttime blood pressure readings were significantly associated with greater risks of death and cardiovascular events that included cardiovascular mortality combined with nonfatal coronary events, heart failure, or stroke. This association persisted after adjusting for other blood pressure measurements taken during an office visit or during ambulatory monitoring.
Higher 24-hour and nighttime blood pressure readings were significantly associated with greater risks of death and a composite of cardiovascular outcomes, although statistically the incremental model improvement was small.
Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes.
To evaluate the association of BP indexes with death and a composite CV event.
Design, Setting, and Participants
Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016).
Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings).
Main Outcomes and Measures
Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC).
Among 11 135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P < .001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP.
Conclusions and Relevance
In this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.
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Corresponding Author: Jan A. Staessen, MD, PhD, Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Kapucijnenvoer 35, BE-3000 Leuven, Belgium (firstname.lastname@example.org).
Accepted for Publication: June 18, 2019.
Author Contributions: Dr Staessen had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Yang, Hansen, Jeppesen, Filipovský, Sandoya, O'Brien, Staessen.
Acquisition, analysis, or interpretation of data: Yang, Melgarejo, Thijs, Zhang, Boggia, Wei, Asayama, Ohkubo, Dolan, Stolarz-Skrzypek, Malyutina, Casiglia, Lind, Filipovský, Maestre, Li, Wang, Imai, Kawecka-Jaszcz, Sandoya, Narkiewicz, Verhamme, Staessen.
Drafting of the manuscript: Yang, Melgarejo, Sandoya, O'Brien, Staessen.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Yang, Melgarejo, Thijs, Wei, Li, Staessen.
Obtained funding: Asayama, Ohkubo, Jeppesen, Casiglia, Maestre, Li, Wang, Narkiewicz, Verhamme, Staessen.
Administrative, technical, or material support: Wei, Ohkubo, Stolarz-Skrzypek, Malyutina, Casiglia, Lind, Maestre, Li, Imai, Sandoya, Narkiewicz, Staessen.
Supervision: Asayama, Ohkubo, Casiglia, Filipovský, Maestre, Imai, Kawecka-Jaszcz, O'Brien, Verhamme, Staessen.
Conflict of Interest Disclosures: Dr Narkiewicz reported receiving lecture fees from Servier, Krka Pharma, Berlin-Chemie/Menarini, Egis, Sandoz, Idorsia, Medtronic, Mylan, Polpharma, Adamed, and Gedeon Richer. No other disclosures were reported.
Funding/Support:Belgium: grants HEALTH-F7-305507 HOMAGE from the European Union; advanced researcher grant 2011-294713-EPLORE and proof-of-concept grant 713601-uPROPHET from the European Research Council, JTC2017-046-PROACT from the European Research Area Net for Cardiovascular Diseases; and G.0881.13 from the Research Foundation Flanders, Ministry of the Flemish Community, Brussels, Belgium; China: grants 81170245, 81270373, 81470533, and 91639203 from the National Natural Science Foundation of China; 2013CB530700 from the Ministry of Science and Technology; 1012 from the China-European Union Collaboration, Beijing, China; 14ZR1436200 and 15XD1503200 from the Shanghai Commission of Science and Technology; and 20152503 from the Gaofeng Clinical Medicine Education; Czech Republic: LSHM-CT-2006–037093 and HEALTH-F4-2007-201550 from the European Union and P36 from Charles University research fund project; Denmark: 01-2-9-9A-22914 from the Danish Heart Foundation and R32-A2740 from the Lundbeck Fonden; Ireland: the Irish Allied Bank; Italy: LSHM-CT-2006-037093 and HEALTH-F4-2007-201550 from the European Union; Japan: 16H05243, 16H05263, 16K09472, 16K11850, 16K15359, 17H04126, 17H06533, 17K15853, 17K19930, 18K09674, 18K09904, and 18K17396 from the Ministry of Culture, Sports, Science and Technology; grant-in-aid H28-4 for young scientists of Showa Pharmaceutical University, Japan Atherosclerosis Prevention Fund (comprehensive research on cardiovascular and lifestyle related diseases); H26-Junkankitou (Seisaku)-Ippan-001 and H29-Junkankitou-Ippan-003 from the Ministry of Health, Labor, and Welfare; NouEi 2-02 from the Ministry of Agriculture, Forestry and Fisheries; Academic Contributions from Pfizer Japan Inc; and scholarship donations from Chugai Pharmaceutical Company and Daiichi Sankyo Co; Poland (Gdańsk): LSHM-CT-2006-037093 and HEALTH-F4-2007-201550 from the European Union; Poland (Kraków): LSHM-CT-2006-037093 and HEALTH-F4-2007-201550 from the European Union and Foundation for Polish Science; Russian Federation: LSHM-CT-2006–037093 and HEALTH-F4-2007–201550 from the European Union; Uruguay: Asociación Española Primera en Salud; Venezuela: 1-R01AG036469 A1 from the US National Institute of Aging and the Fogarty International Center, 1-R03 AG054186-01 from the US National Institutes of Health and National Institute of Aging; FONACIT, G-97000726 from Caracas; and LOCTI/008-2008 from FundaConCiencia, Maracaibo.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
IDACO Investigators: Belgium: B. Mujaj, N. Cauwenberghs, T. Kuznetsova, L. Thijs, J. A. Staessen, F.-F. Wei, W.-Y. Yang, C.-G. Yu, and Z.-Y. Zhang; China: Y. Li, C.-S. Sheng, Q.-F. Huang, and J.-G. Wang; The Czech Republic: J. Filipovský, J. Seidlerová, and M. Tichá; Denmark: T. W. Hansen, H. Ibsen, J. Jeppesen, S. Rasmussen, and C Torp-Pedersen; Ireland: E. Dolan and E. O’Brien; Italy: E. Casiglia, A. Pizzioli, and V. Tikhonoff; Japan: K. Asayama, J. Hashimoto, H. Hoshi, Y. Imai, R. Inoue, M. Kikuya, H. Metoki, T. Obara, T. Ohkubo, H. Satoh, and K. Totsune; Poland (Gdańsk): N. Gilis-Malinowska and K. Narkiewicz; Poland (Kraków): A. Adamkiewicz-Piejko, M. Cwynar, J. Gąsowski, T. Grodzicki, K. Kawecka-Jaszcz, W. Lubaszewski, A. Olszanecka, K. Stolarz-Skrzypek, B. Wizner, W. Wojciechowska, and J. Zyczkowska; The Russian Federation: T. Kuznetsova, S. Malyutina, Y. Nikitin, E. Pello, G. Simonova, and M. Voevoda; Sweden: B. Andrén, L. Berglund, K. Björklund-Bodegård, L. Lind, and B. Zethelius; Uruguay: M. Bianchi, J. Boggia, V. Moreira, E. Sandoya, C. Schettini, E. Schwedt, and H. Senra; Venezuela: G. Maestre and J. D. Melgarejo.
Meeting Presentations: Part of the results was presented at scientific meetings of the European Society of Cardiology, August 25-30, 2018, Munich, Germany, and of the International Society of Hypertension, September 20-23, 2018, Beijing, China.
Additional Contributions: We thank V. De Leebeeck, MSc, and R. Wolfs, BSc, Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium, for clerical assistance. They received a salary from the University of Leuven, but no additional compensation for this work.
Data Sharing Statement: See Supplement 2.
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