Observational and genetic evidence support a relationship between cardiac autonomic function and blood pressure

Zekai Chen; Siqi Wang; Zhen He; Balewgizie S Tegegne; Arie M van Roon; Judith C S Holtjer; Pim van der Harst; Harold Snieder; Chris H L Thio

doi:10.3389/fcvm.2023.1187275

Observational and genetic evidence support a relationship between cardiac autonomic function and blood pressure

Front Cardiovasc Med. 2023 Jun 19:10:1187275. doi: 10.3389/fcvm.2023.1187275. eCollection 2023.

Authors

Zekai Chen¹, Siqi Wang¹, Zhen He¹, Balewgizie S Tegegne^{1

2}, Arie M van Roon³, Judith C S Holtjer⁴, Pim van der Harst^{5

6}, Harold Snieder^#¹, Chris H L Thio^#¹

Affiliations

¹ Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
² Department of Neurology, Center for Statistical Genetics, Gertrude H. Sergievsky Center, Columbia University Medical Center, Columbia University, New York, NY, United States.
³ Department of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
⁴ Department of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, Netherlands.
⁵ Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
⁶ Division of Heart & Lungs, Department of Cardiology, Utrecht University Medical Center, Utrecht University, Utrecht, Netherlands.

^# Contributed equally.

Abstract

Background: It is unclear how cardiac autonomic function, as indicated by heart rate (HR), heart rate variability (HRV), HR increase during exercise, and HR recovery after exercise, is related to blood pressure (BP). We aimed to examine the observational and genetic evidence for a potential causal effect of these HR(V) traits on BP.

Methods: We performed multivariable adjusted linear regression using Lifelines and UK Biobank cohorts to investigate the relationship between HR(V) traits and BP. Linkage disequilibrium score regression was conducted to examine genetic correlations. We used two-sample Mendelian randomization (2SMR) to examine potential causal relations between HR(V) traits and BP.

Results: Observational analyses showed negative associations of all HR(V) traits with BP, except for HR, which was positively associated. Genetic correlations were directionally consistent with the observational associations, but most significant genetic correlations between HR(V) traits and BP were limited to diastolic blood pressure (DBP). 2SMR analyses suggested a potentially causal relationship between HR(V) traits and DBP but not systolic blood pressure (SBP). No reverse effect of BP on HR(V) traits was found. One standard deviation (SD) unit increase in HR was associated with a 1.82 mmHg elevation of DBP. In contrast, one ln(ms) unit increase of the root mean square of the successive differences (RMSSD) and corrected RMSSD (RMSSDc), decreased DBP by 1.79 and 1.83 mmHg, respectively. For HR increase and HR recovery at 50 s, every additional SD increase was associated with a lower DBP by 2.05 and 1.47 mmHg, respectively. Results of secondary analyses with pulse pressure as outcome were inconsistent between observational and 2SMR analyses, as well as between HR(V) traits, and therefore inconclusive.

Conclusion: Both observational and genetic evidence show strong associations between indices of cardiac autonomic function and DBP, suggesting that a larger relative contribution of the sympathetic versus the parasympathetic nervous system to cardiac function may cause elevated DBP.

Keywords: blood pressure; cardiac autonomic function; heart rate; heart rate variability; two-sample Mendelian randomization.

Grants and funding

ZC is supported by a joint fellowship from the China Scholarship Council and University Medical Center Groningen (no. 202008440344).