Lifestyle and heart rate variability in the general population

Background: Cardiovascular diseases (CVD) are among the main causes of death worldwide. An unhealthy lifestyle, sleep-related breathing disorders and inflammation are all significantly and independently associated with an increased risk of cardiovascular events.
The autonomic nervous system (ANS) is an important player within the cardiovascular system. Over the last years, heart rate variability (HRV) has become a validated measure of the autonomic function and was found to be associated with several cardiovascular risk factors, disease outcomes and mortality. To date, several aspects related to HRV among young adults remain unclear.
Based on those gaps of knowledge, the general aim of this PhD thesis was to assess the relationships of HRV with lifestyle, sleep-related breathing disorders and inflammatory biomarkers among young and healthy adults from the general population. The specific aims were 1) to evaluate the prevalence of a healthy lifestyle and assess its relationship with HRV, 2) to assess the prevalence of sleep-related breathing disorders and investigate its association with HRV and 3) to assess the interrelationships between HRV and blood markers of inflammation.
Methods: This PhD thesis is based on data from the Genetic and Phenotypic Determinants of Blood Pressure and other Cardiovascular Risk Factors (GAPP) study, a prospective population based cohort study. Overall, 2170 inhabitants of the Principality of Liechtenstein, aged between 25-41 years, without established CVD and a BMI ≤35kg/m2 were included in this study. Study participants obtained a 24-hour (h) Holter electrocardiogram (ECG), and careful post-processing was applied. Time- and frequency domain HRV variables and ambulatory heart rate (HR) were exported. The standard deviation of all normal RR intervals (SDNN) was pre-specified as the main HRV variable for all analyses. Personal, medical, lifestyle and nutritional information were assessed using standardized questionnaires. A fasting venous blood sample was taken to determine biomarkers. For assessment of sleep-related breathing disorders, a nocturnal pulse oximetry with additional nasal airflow recording was performed. Resting HR was recorded using a 10-second resting ECG. Multivariable linear regression models were constructed using HRV related parameters as the outcome variables.
Results: Overall, 2170 participants (47% male) with a median age of 37 years were included. We found that only 11% of our population adopted a healthy lifestyle defined as a lifestyle-score of 6 or 7, whereas 5% had a very unhealthy lifestyle defined as a score of 0 or 1. In general, women had a higher lifestyle-score compared to men. Having a healthy lifestyle was significantly associated with SDNN, with a β-coefficient (95% confidence interval (CI)) of 0.14 (0.11; 0.17), p=0.0001 per one point increase in the lifestyle-score. This result was attenuated but remained significant after additional adjustment for either resting or ambulatory HR. In the second analysis we found that 9.6% of the population had an apnea-hypopnea index (AHI) ≥5, which is one important component for the diagnosis of an obstructive sleep apnea syndrome. After comprehensive multivariable adjustment, SDNN was inversely associated with categories of AHI and oxygen desaturation index (ODI). These relationships were strongly weakened after the additional adjustment for resting and 24-h HR and most of these relationships lost significance. Resting and ambulatory HR by itself were positively associated with increasing levels of AHI and ODI categories. However, only the relationships with ambulatory HR remained significant after the adjustment for HRV. In the final analysis, we found a close and independent link between HRV and inflammatory biomarkers. Inverse associations of SDNN with all available inflammatory biomarkers were found, with β-coefficients (95%CI) of -0.11 (-0.16;-0.07), p<0.0001 for high-sensitivity C-reactive protein, -0.13 (-0.17;-0.09), p<0.0001 for total leukocyte count, -0.12 (-0.16;-0.08), p<0.0001 for neutrophils, -0.04 (-0.09;0.00), p=0.05 for lymphocytes and -0.08 (-0.09;-0.02), p=0.005 for monocytes. These associations were strongly attenuated after additional adjustment for ambulatory HR and partly lost significance. Ambulatory HR by itself was positively associated with all inflammatory biomarkers, except lymphocytes.
Conclusion: In this young and healthy population, HRV was significantly related to a comprehensive healthy lifestyle, sleep-related breathing disorders and inflammatory biomarkers, suggesting an interrelationship between the ANS and these entities. However, most of the information seems to be contained in HR, and the incremental information of HRV parameters was modest in most analyses. These data may allow some insights in the pathophysiology of CVD occurrence. Finally, the adoption of a healthy lifestyle was rather low in this population, underscoring the importance of healthy lifestyle promotion in the society.
Outlook: More data are needed on the role of the autonomic function in the development of CVD outcomes and on the independent role of HRV in the prediction of cardiovascular risk factor progression or outcome occurrence.