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Associations of time of day with cardiovascular disease risk factors measured in older men: results from the British Regional Heart Study


Objective We estimated associations of time of day with cardiovascular disease (CVD) risk factors measured in older men.

Methods CVD risk factors (markers of inflammation and haemostasis, and cardiac markers) were measured on one occasion between 08:00 and 19:00 hours in 4252 men aged 60–79 years from the British Regional Heart Study. Linear models were used to estimate associations between time of day and risk factors. When an association was found, we examined whether the relationship between risk factors and cardiovascular mortality was affected by the adjustment for time of day using survival analyses.

Results N-terminal pro-brain natriuretic peptide (NT-proBNP) levels increased by 3.3% per hour (95% CI 1.9% to 4.8%), interleukin-6 (IL-6) increased by 2.6% per hour (95% CI 1.8% to 3.4%), while tissue plasminogen activator (t-PA) decreased by 3.3% per hour (95% CI 3.7% to 2.9%); these associations were unaffected by adjustment for possible confounding factors. The percentages of variation in these risk factors attributable to time of day were less than 2%. In survival analyses, the association of IL-6, NT-proBNP and t-PA with cardiovascular mortality was not affected by the adjustment for time of day. C reactive protein, fibrinogen, D-dimer, von Willebrand factor and cardiac troponin T showed no associations with time of day.

Conclusions In older men, markers of inflammation (IL-6), haemostasis (t-PA) and a cardiac marker (NT-proBNP) varied by time of day. The contribution of time of day to variations in these markers was small and did not appear to be relevant for the CVD risk prediction.

  • Biological Markers
  • Older Adults
  • Cardiovascular Disease
  • Diurnal Variations

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  • Contributors CS processed the data, performed statistical analyses, drafted and revised the manuscript and incorporated revisions of coauthors. PHW, SGW, BJJ and RWM contributed to the design of the study and revised the manuscript. LL enrolled participants and collected data. PHW, RWM and GSW raised grant funding. All authors gave an intellectual contribution to the manuscript and approved the final version.

  • Funding The BRHS is supported by a British Heart Foundation (BHF) programme grant (RG/13/16/30528). This research was supported by a BHF project grant (PG/13/41/30304), which supported CS. 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 the decision to submit the manuscript for publication.

  • Disclaimer The views expressed in this publication are those of the author(s) and not necessarily those of the BHF.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The National Research Ethics Service (NRES) Committee for London provided ethical approval.

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

  • Data sharing statement The collection and management of data over the last 39 years of the BRHS has been made possible through grant funding from UK government agencies and charities. We welcome proposals for collaborative projects and data sharing. For general data sharing enquiries, please contact Lucy Lennon at

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