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Multi-morbidity and blood pressure trajectories in hypertensive patients: A multiple landmark cohort study

Lookup NU author(s): Dr Dexter CanoyORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2021 Tran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Our knowledge of how to better manage elevated blood pressure (BP) in the presence of comorbidities is limited, in part due to exclusion or underrepresentation of patients with multiple chronic conditions from major clinical trials. We aimed to investigate the burden and types of comorbidities in patients with hypertension and to assess how such comorbidities and other variables affect BP levels over time. Methods and findings In this multiple landmark cohort study, we used linked electronic health records from the United Kingdom Clinical Practice Research Datalink (CPRD) to compare systolic blood pressure (SBP) levels in 295,487 patients (51% women) aged 61.5 (SD = 13.1) years with first recorded diagnosis of hypertension between 2000 and 2014, by type and numbers of major comorbidities, from at least 5 years before and up to 10 years after hypertension diagnosis. Time-updated multivariable linear regression analyses showed that the presence of more comorbidities was associated with lower SBP during follow-up. In hypertensive patients without comorbidities, mean SBP at diagnosis and at 10 years were 162.3 mm Hg (95% confidence interval [CI] 162.0 to 162.6) and 140.5 mm Hg (95% CI 140.4 to 140.6), respectively; in hypertensive patients with ≥5 comorbidities, these were 157.3 mm Hg (95% CI 156.9 to 157.6) and 136.8 mm Hg (95% 136.4 to 137.3), respectively. This inverse association between numbers of comorbidities and SBP was not specific to particular types of comorbidities, although associations were stronger in those with preexisting cardiovascular disease. Retrospective analysis of recorded SBP showed that the difference in mean SBP 5 years before diagnosis between those without and with ≥5 comorbidities was -9 mm Hg (95% CI -9.7 to -8.3), suggesting that mean recorded SBP already differed according to the presence of comorbidity before baseline. Within 1 year after the diagnosis, SBP substantially declined, but subsequent SBP changes across comorbidity status were modest, with no evidence of a more rapid decline in those with more or specific types of comorbidities. We identified factors, such as prescriptions of antihypertensive drugs and frequency of healthcare visits, that can explain SBP differences according to numbers or types of comorbidities, but these factors only partly explained the recorded SBP differences. Nevertheless, some limitations have to be considered including the possibility that diagnosis of some conditions may not have been recorded, varying degrees of missing data inherent in analytical datasets extracted from routine health records, and greater measurement errors in clinical measurements taken in routine practices than those taken in well-controlled clinical study settings. Conclusions BP levels at which patients were diagnosed with hypertension varied substantially according to the presence of comorbidities and were lowest in patients with multi-morbidity. Our findings suggest that this early selection bias of hypertension diagnosis at different BP levels was a key determinant of long-term differences in BP by comorbidity status. The lack of a more rapid decline in SBP in those with multi-morbidity provides some reassurance for BP treatment in these high-risk individuals.

Publication metadata

Author(s): Tran J, Norton R, Canoy D, Solares JRA, Conrad N, Nazarzadeh M, Raimondi F, Salimi-Khorshidi G, Rodgers A, Rahimi K

Publication type: Article

Publication status: Published

Journal: PLoS Medicine

Year: 2021

Volume: 18

Issue: 6

Print publication date: 17/06/2021

Online publication date: 17/06/2021

Acceptance date: 25/05/2021

Date deposited: 25/11/2022

ISSN (print): 1549-1277

ISSN (electronic): 1549-1676

Publisher: Public Library of Science


DOI: 10.1371/journal.pmed.1003674

PubMed id: 34138851


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Funder referenceFunder name
... UKRI’s Global Challenge Research Fund, Grant Ref: ES/P011055/1.
JT was supported by the Rhodes Trust and Clarendon Fund for this work. MN received support from the British Heart Foundation (grant number: FS/19/36/34346),
KR is in receipt of grants from: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre; the Oxford Martin School; the British Heart Foundation and...
National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Oxford Martin School
NC is supported by a fellowship from the Marie Skłodowska-Curie Actions programme and a grant from the European Society of Cardiology, outside of this work