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Interpreting resting heart rate variability in complex populations: the role of autonomic reflexes and comorbidities

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Abstract

Purpose

Resting heart rate variability (HRV) is an important biomarker linking mental health to cardiovascular outcomes. However, resting HRV is also impaired in autonomic neuropathy, a common and underdiagnosed complication of common medical conditions which is detected by testing autonomic reflexes. We sought to describe the relationship between autonomic reflex abnormalities and resting HRV, taking into consideration medical comorbidities and demographic variables.

Methods

Participants (n = 209) underwent a standardized autonomic reflex screen which was summarized as the Composite Autonomic Severity Score (CASS) and included measures of reflexive HRV, e.g., heart rate with deep breathing (HRDB). Resting HRV measures were: pNN50 (percentage of NN intervals that differ by > 50 ms) and cvRMSSD (adjusted root mean square of successive differences).

Results

In univariate analyses, lower resting HRV was associated with: older age, higher CASS, neuropathy on examination, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, and psychiatric disease. Adaptive regression spline analysis revealed that HRDB explained 27% of the variability in resting HRV for participants with values of HRDB in the normal range. Outside this range, there was no linear relationship because: (1) when HRDB was low (indicating autonomic neuropathy), resting HRV was also low with low variance; and (2) when HRDB was high, the variance in resting HRV was high. In multivariate models, only HRDB was significantly independently associated with cvRMSSD and pNN50.

Conclusion

Subclinical autonomic neuropathy, as evidenced by low HRDB and other autonomic reflexes, should be considered as a potential confounder of resting HRV in research involving medically and demographically diverse populations.

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Acknowledgements

This research was supported in part by National Institutes of Health grants R01DK122853 and R21DK105917.

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Authors and Affiliations

  1. Department of Neurology, NYU Grossman School of Medicine, 8714 5th Ave 2nd Floor, Brooklyn, NY, 11209, USA

    Patrick M. Kwon

  2. Center for Biostatistics and Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Steven Lawrence & Emma K. T. Benn

  3. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Bridget R. Mueller & Jessica Robinson-Papp

  4. Department of Psychological Science, School of Social Ecology, University of California at Irvine, Irvine, CA, USA

    Julian F. Thayer

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  1. Patrick M. Kwon
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  2. Steven Lawrence
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  3. Bridget R. Mueller
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  4. Julian F. Thayer
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  5. Emma K. T. Benn
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  6. Jessica Robinson-Papp
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Contributions

Study conception, design, material preparation, data collection, and analysis were performed by PK, SL, BM and JR-P. Study conception, design and analysis was performed by JFT and EKTB. The first draft of the manuscript was written by PK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Patrick M. Kwon.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

All human and studies have been approved by the appropriate ethics committee and therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Kwon, P.M., Lawrence, S., Mueller, B.R. et al. Interpreting resting heart rate variability in complex populations: the role of autonomic reflexes and comorbidities. Clin Auton Res 32, 175–184 (2022). https://doi.org/10.1007/s10286-022-00865-2

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  • DOI: https://doi.org/10.1007/s10286-022-00865-2

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