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Original research
Symptoms and signs in patients with heart failure: association with 3-month hospitalisation and mortality
  1. Mohammad Rizwan Ali1,2,3,
  2. Carolyn S P Lam4,5,
  3. Anna Strömberg6,7,
  4. Simon P P Hand8,
  5. Sarah Booth8,
  6. Francesco Zaccardi3,9,
  7. Iain Squire1,10,
  8. Gerry P McCann1,2,
  9. Kamlesh Khunti3,11,
  10. Claire Alexandra Lawson1,2
  1. 1 Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
  2. 2 NIHR Leicester Cardiovascular Biomedical Research Unit, NIHR Leicester Biomedical Research Centre, Leicester, UK
  3. 3 Leicester Real World Evidence Unit, University of Leicester, Leicester, UK
  4. 4 Department of Cardiology, National Heart Centre Singapore, Singapore
  5. 5 Medical School, National University of Singapore, Singapore
  6. 6 Department of Medical and Health Science, Linkopings universitet, Linkoping, Sweden
  7. 7 Faculty of Medicine, Linkoping University, Linkoping, Sweden
  8. 8 Department of Population Health Sciences, University of Leicester, Leicester, UK
  9. 9 Diabetes Research Centre, University of Leicester, Leicester, UK
  10. 10 Cardiovascular Research Unit, NIHR Leicester Biomedical Research Centre, Leicester, UK
  11. 11 Leicester Diabetes Centre, University of Leicester, Leicester, UK
  1. Correspondence to Mohammad Rizwan Ali, Department of Cardiovascular Sciences, University of Leicester, Leicester LE1 7RH, UK; mra30{at}leicester.ac.uk

Abstract

Objectives To determine the association between symptoms and signs reported in primary care consultations following a new diagnosis of heart failure (HF), and 3-month hospitalisation and mortality.

Design Nested case–control study with density-based sampling.

Setting Clinical Practice Research Datalink, linked to hospitalisation and mortality (1998–2020).

Participants Database cohort of 86 882 patients with a new HF diagnosis. In two separate analyses for (1) first hospitalisation and (2) death, we compared the 3-month history of symptoms and signs in cases (patients with HF with the event), with their respective controls (patients with HF without the respective event, matched on diagnosis date (±1 month) and follow-up time). Controls could be included more than once and later become a case.

Main outcome measures All-cause, HF and non-cardiovascular disease (non-CVD) hospitalisation and mortality.

Results During a median follow-up of 3.22 years (IQR: 0.59–8.18), 56 677 (65%) experienced first hospitalisation and 48 146 (55%) died. These cases were matched to 356 714 and 316 810 HF controls, respectively. For HF hospitalisation, the strongest adjusted associations were for symptoms and signs of fluid overload: pulmonary oedema (adjusted OR 3.08; 95% CI 2.52, 3.64), shortness of breath (2.94; 2.77, 3.11) and peripheral oedema (2.16; 2.00, 2.32). Generic symptoms also showed significant associations: depression (1.50; 1.18, 1.82), anxiety (1.35; 1.06, 1.64) and pain (1.19; 1.10, 1.28). Non-CVD hospitalisation had the strongest associations with chest pain (2.93; 2.77, 3.09), fatigue (1.87; 1.73, 2.01), general pain (1.87; 1.81, 1.93) and depression (1.59; 1.44, 1.74).

Conclusions In the primary care HF population, routinely recorded cardiac and non-specific symptoms showed differential risk associations with hospitalisation and mortality.

  • heart failure
  • epidemiology

Data availability statement

Data may be obtained from a third party and are not publicly available. In accordance with the principles of open science and data transparency, we recognise the importance of data sharing. However, we regretfully cannot share the data associated with this study due to the terms of access when we applied for the data via the CPRD. We appreciate the value of data accessibility and encourage any interested parties to contact us to discuss potential collaborations or alternative approaches to address data queries they may have.

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Data availability statement

Data may be obtained from a third party and are not publicly available. In accordance with the principles of open science and data transparency, we recognise the importance of data sharing. However, we regretfully cannot share the data associated with this study due to the terms of access when we applied for the data via the CPRD. We appreciate the value of data accessibility and encourage any interested parties to contact us to discuss potential collaborations or alternative approaches to address data queries they may have.

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Footnotes

  • Twitter @mo_r_ali

  • Contributors MRA— guarantor of the research, literature search, study design, data analysis, data interpretation, figures and writing. CSPL—data interpretation and writing. AS—data interpretation and writing. SPPH—figures, data interpretation and writing. SB—figures, study design, data interpretation and writing. FZ—study design, data interpretation and writing. IS—data interpretation and writing. GPM—data interpretation and writing. KK—study design, data interpretation and writing. CAL—literature search, study design, data analysis, data interpretation, figures and writing.

  • Funding The research was supported by a National Institute for Health Research (NIHR) Advanced Fellowship (reference NIHR300111). KK is supported by the NIHR Applied Research Collaboration East Midlands (ARC EM) and the NIHR Leicester Biomedical Research Centre (BRC).

  • Competing interests CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Novo Nordisk and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Alleviant Medical, Allysta Pharma, Amgen, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, CardioRenal, Cytokinetics, Darma, EchoNous, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development, Medscape/WebMD Global, Merck, Novartis, Novo Nordisk, Prosciento, Radcliffe Group, Recardio, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as co-founder and non-executive director of Us2.ai. KK has acted as a consultant, speaker or received grants for investigator-initiated studies for AstraZeneca, Bayer, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Oramed Pharmaceuticals, Roche and Applied Therapeutics.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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