Are Changes in Heart Rate Variability in Middle-Aged and Older People Normative or Caused by Pathological Conditions? Findings From a Large Population-Based Longitudinal Cohort Study.

BACKGROUND: No study to date has investigated longitudinal trajectories of cardiac autonomic modulation changes with aging; therefore, we lack evidence showing whether these changes occur naturally or are secondary to disease or medication use. This study tested whether heart rate variability (HRV) trajectories from middle to older age are largely normative or caused by pathological changes with aging in a large prospective cohort. We further assessed whether HRV changes were modified by socioeconomic status, ethnicity, or habitual physical activity. METHODS AND RESULTS: This study involved 3176 men and 1238 women initially aged 44 to 69 years (1997-1999) from the UK Whitehall II population-based cohort. We evaluated time- and frequency-domain HRV measures of short-term recordings at 3 time points over a 10-year period. Random mixed models with time-varying covariates were applied. Cross-sectionally, HRV measures were lower for men than for women, for participants with cardiometabolic conditions, and for participants reporting use of medications other than beta blockers. Longitudinally, HRV measures decreased significantly with aging in both sexes, with faster decline in younger age groups. HRV trajectories were not explained by increased prevalence of cardiometabolic problems and/or medication use. In women, cardiometabolic problems were associated with faster decline in the standard deviation of all intervals between R waves with normal-to-normal conduction, in low-frequency HRV, and in low-frequency HRV in normalized units. Socioeconomic status, ethnicity, and habitual physical activity did not have significant effects on HRV trajectories. CONCLUSIONS: Our investigation showed a general pattern and timing of changes in indices of cardiac autonomic modulation from middle to older age. These changes seem likely to reflect the normal aging process rather than being secondary to cardiometabolic problems and medication use

Heart rate variability and depressive symptoms: a cross-lagged analysis over a 10-year period in the Whitehall II study

BACKGROUND: People with depression tend to have lower heart rate variability (HRV), but the temporal sequence is poorly understood. In a sample of the general population, we prospectively examined whether HRV measures predict subsequent depressive symptoms or whether depressive symptoms predict subsequent levels of HRV. METHOD: Data from the fifth (1997-1999) and ninth (2007-2009) phases of the UK Whitehall II longitudinal population-based cohort study were analysed with an average follow-up of 10.5 years. The sample size for the prospective analysis depended on the analysis and ranged from 2334 (644 women) to 2276 (602 women). HRV measures during 5 min of supine rest were obtained. Depressive symptoms were evaluated by four cognitive symptoms of depression from the General Health Questionnaire. RESULTS: At follow-up assessment, depressive symptoms were inversely associated with HRV measures independently of antidepressant medication use in men but not in women. Prospectively, lower baseline heart rate and higher HRV measures were associated with a lower likelihood of incident depressive symptoms at follow-up in men without depressive symptoms at baseline. Similar but statistically insignificant associations were found in women. Adjustments for known confounders including sociodemographic and lifestyle factors, cardiometabolic conditions or medication did not change the predictive effect of HRV on incident depressive symptoms at follow-up. Depressive symptoms at baseline were not associated with heart rate or HRV at follow-up in either sex. CONCLUSIONS: These findings are consistent with an aetiological role of the autonomic nervous system in depression onset

Healthy Lifestyle and Cardiac Vagal Modulation Over 10 Years: Whitehall II Cohort Study

Background: Increased vagal modulation is a mechanism that may partially explain the protective effect of healthy lifestyles. However, it is unclear how healthy lifestyles relate to vagal regulation longitudinally. We prospectively examined associations between a comprehensive measure of 4 important lifestyle factors and vagal modulation, indexed by heart rate variability (HRV) over 10 years. / Methods and Results: The fifth (1997–1999), seventh (2002–2004), and ninth (2007–2009) phases of the UK Whitehall II cohort were analyzed. Analytical samples ranged from 2059 to 3333 (mean age: 55.7 years). A healthy lifestyle score was derived by giving participants 1 point for each healthy factor: physically active, not smoking, moderate alcohol consumption, and healthy body mass index. Two vagally mediated HRV measures were used: high‐frequency HRV and root mean square of successive differences of normal‐to‐normal R‐R intervals. Cross‐sectionally, a positively graded association was observed between the healthy lifestyle score and HRV at baseline (Poverall≤0.001). Differences in HRV according to the healthy lifestyle score remained relatively stable over time. Compared with participants who hardly ever adhered to healthy lifestyles, those with consistent healthy lifestyles displayed higher high‐frequency HRV (β=0.23; 95% CI, 0.10–0.35; P=0.001) and higher root mean square of successive differences of normal‐to‐normal R‐R intervals (β=0.15; 95% CI, 0.07–0.22; P≤0.001) at follow‐up after covariate adjustment. These differences in high‐frequency HRV and root mean square of successive differences of normal‐to‐normal R‐R intervals are equivalent to ≈6 to 20 years differences in chronological age. Compared with participants who reduced their healthy lifestyle scores, those with stable scores displayed higher subsequent high‐frequency HRV (β=0.24; 95% CI, 0.01–0.48; P=0.046) and higher root mean square of successive differences of normal‐to‐normal R‐R intervals (β=0.15; 95% CI, 0.01–0.29; P=0.042). / Conclusions: Maintaining healthy lifestyles is positively associated with cardiac vagal functioning, and these beneficial adaptations may be lost if not sustained

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020).

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice

Potential biological pathways linking Type-D personality and poor health: A cross-sectional investigation

Type-D personality, defined as a combination of high negative affect and high social isolation, has been associated with poor health outcomes. However, pathways underlying this association are largely unknown. We investigated the relationship between Type-D personality and several biological and behavioral pathways including the autonomic nervous system, the immune system, glucose regulation and sleep in a large, apparently healthy sample.Data from a total of 646 respondents (age 41.6±11.5, 12,2% women) were available for analysis. Persons with Type-D (negative affect and social isolation score ≥10) were contrasted with those without Type-D. Measures of plasma fibrinogen levels, white blood cell count, high sensitivity C-reactive protein, fasting plasma glucose (FPG), cholesterol, high-density and low-density lipoprotein, glycated hemoglobin (HbA1c), creatinine, triglycerides, and albumin were derived from fasting blood samples. Urine norepinephrine and free cortisol were determined by high-performance liquid chromatography. Time-domain heart rate variability (HRV) measures were calculated for the 24hr recording period and for nighttime separately.Persons with Type-D had higher HbA1c, FPG, and fibrinogen, and lower nighttime HRV than those without Type-D, suggesting worse glycemic control, systemic inflammation and poorer autonomic nervous system modulation in Type-D persons. In addition, those with Type-D reported less social support and greater sleep difficulties while no group differences were observed for alcohol and cigarette consumption, physical activity and body mass index.Findings provide some of the first evidence for multiple possible biological and behavioral pathways between Type-D personality and increased morbidity and mortality

International consensus based review and recommendations for minimum reporting standards in research on transcutaneous vagus nerve stimulation (version 2020)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice