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Autonomic dysfunction is associated with the development of arterial stiffness: the Whitehall II cohort

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Abstract

This study aims to examine the association between baseline level and change of autonomic nervous function with subsequent development of arterial stiffness. Autonomic nervous function was assessed in 4901 participants of the Whitehall II occupational cohort by heart rate variability (HRV) indices and resting heart rate (rHR) three times between 1997 and 2009, while arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) measured twice between 2007 and 2013. First, individual HRV/rHR levels and annual changes were estimated. Then, we modelled the development of PWV by HRV/rHR using linear mixed effect models. First, we adjusted for sex and ethnicity (model 1), and then for socioeconomic and lifestyle factors, various clinical measurements, and medications (model 2). A decrease in HRV and unchanged rHR was associated with subsequent higher levels of PWV, but the effect of a change in HRV was less pronounced at higher ages. A typical individual aged 65 years with a SDNN level of 30 ms and a 2% annual decrease in SDNN had 1.32 (0.95; 1.69) higher PWV compared to one with the same age and SDNN level but with a 1% annual decrease in SDNN. Further adjustment had no major effect on the results. People who experience a steeper decline in autonomic nervous function have higher levels of arterial stiffness. The association was stronger in younger people.

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Data availability

Whitehall II data, protocols and other metadata are available to bona fide researchers for research purposes. Please refer to the Whitehall II data sharing policy at https://www.ucl.ac.uk/epidemiology-health-care/research/epidemiology-and-public-health/research/whitehall-ii/data-sharing.

Abbreviations

CAN:

Cardiovascular autonomic neuropathy

CVD:

Cardiovascular disease

ECG:

Electrocardiogram

HF power:

High-frequency power

HRV:

Heart rate variability

LF power:

Low-frequency power

PWV:

Carotid-femoral pulse wave velocity

rHR:

Resting heart rate

RMSSD:

The root mean square of the sum of the squares of differences between consecutive normal-to-normal R-R intervals

SDNN:

The standard deviation of normal-to-normal R-R intervals

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Acknowledgements

We thank all participating women and men in the Whitehall II Study, as well as all Whitehall II research scientists, study and data managers and clinical and administrative staff who make the study possible.

Funding

The UK Medical Research Council (K013351, R024227), British Heart Foundation and the US National Institutes of Health (R01HL36310, R01AG013196) have supported collection of data in the Whitehall II study. JFRS, DRW, AH and LB are employed at Steno Diabetes Center Aarhus, and CSH and DV are employed at Steno Diabetes Center Copenhagen. Both institutions are partly funded by a donation from the Novo Nordisk Foundation. The funders had no role in the design of the study. DRW and JRS are supported by EFSD/Sanofi European Diabetes Research Programme in diabetes associated with cardiovascular disease. AGT was supported by the UK Medical Research Council (S011676), NordForsk (the Nordic Research Programme on Health and Welfare, 75021), and by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund (2021 Thematic Excellence Programme funding scheme, TKP2021-NKTA-47).

Author information

Authors and Affiliations

  1. Department of Public Health, Aarhus University, Bartholins Allé 2, 8000, Aarhus, Denmark

    Jonas R. Schaarup, Adam Hulman, Daniel R. Witte & Lasse Bjerg

  2. Steno Diabetes Center Aarhus, Aarhus University Hospital, Palle Juul-Jensens Boulevard 11, 8200, Aarhus, Denmark

    Jonas R. Schaarup, Adam Hulman, Daniel R. Witte & Lasse Bjerg

  3. Aarhus University Hospital, Palle Juul-Jensens Boulevard 161, 8200, Aarhus, Denmark

    Martin S. Christensen

  4. Steno Diabetes Center Copenhagen, Ib Juuls Vej 83, 2730, Herlev, Denmark

    Christian S. Hansen & Dorte Vistisen

  5. Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, 1353, Copenhagen, Denmark

    Dorte Vistisen

  6. Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, UK

    Adam G. Tabák

  7. Department of Public Health, Semmelweis University Faculty of Medicine, 26 Üllői Str., 1085, Budapest, Hungary

    Adam G. Tabák

  8. Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, 26 Üllői Str., 1085, Budapest, Hungary

    Adam G. Tabák

Authors
  1. Jonas R. Schaarup
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  2. Martin S. Christensen
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  4. Christian S. Hansen
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  5. Dorte Vistisen
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  6. Adam G. Tabák
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  7. Daniel R. Witte
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  8. Lasse Bjerg
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Contributions

Study concept and design: JRS, DRW, AH, MSC, LB, DV and CSH. Contributed the data: DRW and AGT. Planning the statistical analysis: JRS, DRW, AH, LB, MSC and DV. Conducted the statistical analysis: JRS. All authors contributed to, critically revised and approved the final version of the manuscript. JRS is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Jonas R. Schaarup.

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Ethics approval

The UK NHS Health Research Authority London-Harrow ethics committee approved the study, which was conducted in accordance with the Helsinki Declaration with written informed consent from all participants.

Conflict of interest

The authors declare no competing interests.

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Schaarup, J.R., Christensen, M.S., Hulman, A. et al. Autonomic dysfunction is associated with the development of arterial stiffness: the Whitehall II cohort. GeroScience 45, 2443–2455 (2023). https://doi.org/10.1007/s11357-023-00762-0

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