OBJECTIVE -Measures of baroreflex sensitivity, heart rate variability (HRV), and the classical Ewing test parameters are currently used for the diagnosis of diabetic autonomic neuropathy and for mortality risk stratification after myocardial infarction. However, the strengths of the associations of these measures of autonomic function with risk of mortality have never been compared in one study population. Furthermore, no evidence is available on the possible effect of glucose tolerance on these associations. RESEARCH DESIGN AND METHODS-The study population (n ϭ 605) consisted of a glucose tolerance-stratified sample from a general population (50 -75 years of age). Cardiac cycle duration and continuous finger arterial pressure were measured under two conditions: at rest and on metronome breathing. From these readings, seven parameters of autonomic function were assessed (one Ewing, five HRV, and one baroreflex sensitivity).RESULTS -During 9 years of follow-up, 101 individuals died, 43 from cardiovascular causes. Subjects with diabetes and low levels of the autonomic function parameters, indicating impaired autonomic function, had an approximately doubled risk of mortality. This association was consistent, though not statistically significant, for all parameters. The elevated risk was not observed in subjects without diabetes, hypertension, or prevalent cardiovascular disease.CONCLUSIONS -Impaired autonomic function is associated with all-cause and cardiovascular mortality. Moreover, the results of the present study suggest that cardiac autonomic dysfunction in patients already at risk (diabetes, hypertension, or history of cardiovascular disease) may be especially hazardous.

Aims/hypothesis. Currently, three categories of measures are used to assess cardiovascular autonomic dysfunction: measures of the Ewing-test, measures of heart-rate variability, and measures of baroreflex sensitivity. We studied the determinants of these measures obtained from cardiovascular autonomic function tests in the Hoorn Study. Methods. The study group (n = 631) consisted of a glucose-tolerance-stratified sample from a 50-to 75-year-old group of people. Cardiac cycle duration (RR interval) and continuous finger arterial pressure were measured under three conditions: during (a) spontaneous breathing, (b) six deep breaths over one minute, and (c) an active change in position from lying to standing. From these readings, ten measures of autonomic function were assessed (three Ewing, six heart-rate variability and one baroreflex sensitivity). As possible determinants we considered age, sex, glucose tolerance, cardiovascular disease, use of anti-hypertensive drugs, anthropometric factors, metabolic factors and lifestyle factors.Results. Multivariate analysis showed that eight of ten cardiovascular autonomic function measures were most strongly associated with glucose tolerance. Furthermore, measures were moderately associated with age, sex, waist-to-hip ratio, use of anti-hypertensive drugs, and insulin. The measures were weakly associated with coronary artery disease but not with lipids. The strongest determinants seemed to differ between subjects with and without diabetes: in the non-diabetic subjects the most strongly associated were age and use of anti-hypertensive drugs and in subjects with diabetes, insulin. No consistent differences in association between the three categories of measures were observed. Conclusion/interpretation. The strongest determinants of autonomic function were age, presence of diabetes and use of anti-hypertensive drugs. [Diabetologia (2000) 43: 561±570]Keywords Aging, baroreflex, Type II diabetes mellitus, cardiovascular disease, glucose intolerance, heart-rate variability, hypertension, lifestyle, autonomic nervous system, obesity. Abbreviations: BRS, Baroreflex sensitivity (ms/mmHg); DM, diabetes mellitus; EI difference, expiration-inspiration difference in RR intervals during breathing at 6/min (ms); HRV, heart-rate variability; HF power, high frequency power in the RR-interval spectrum between 0.12±0.40 Hz (ms 2 ); KDM, known diabetes mellitus; LF power, low frequency power in the RR-interval spectrum between 0.04±0.12 Hz (ms 2 ); LF/ (LF + HF), ratio of low frequency power to the sum of low and high frequency power in the RR-interval spectrum; Mean NN, mean of all sinus rhythm (normal-to-normal) RR intervals (ms); NDM, newly-diagnosed diabetes mellitus; RRmax, maximal change in RR interval after standing up (ms); RRmax/min, maximal RR interval between 15 s and 30 s after standing up divided by the minimal RR interval within 15 s after standing up; SBP difference, systolic blood pressure 1.5±2 min after standing up minus systolic blood pressure in supine position (mm...

Controlled 6/min breathing caused significant BRS overestimation under resting conditions. For the group, spontaneous respiration yielded acceptable BRS values, but individual BRS values deviated sometimes considerably. Conversely, with gravitational load, the respiratory pattern had only minor impact on BRS. Our results demonstrate that the risk of an overestimated BRS value is realistic as long as respiration is not controlled and of high-frequency.

Aims/hypothesis. Currently, three categories of cardiovascular autonomic nervous function measures are used: classic Ewing-test measures, measures of heartrate variability (HRV), and measures of baroreflex sensitivity (BRS). Little is known about the agreement between these measures, and reference and reproducibility values for these measures have not been reported within the same group. Methods. As part of the Hoorn Study, 631 subjects aged 50 to 75 participated in a study of autonomic nervous function. Cardiac cycle duration (RR interval) and continuous finger arterial pressure were measured under three conditions: during spontaneous breathing, during six deep breaths over 1 min, and during an active change in position from lying to standing. From these readings, ten measures of autonomic function were assessed (mean heart rate, three Ewing test measures, five HRV measures and one BRS measure). Results. Regression analysis in a healthy subgroup (n=191) showed sex differences for two of the ten measures and seven measures decreased with age. Therefore, appropriate age-specific and sex-specific reference values were calculated. Reproducibility (n=39) of most measures was moderate, with a reliability coefficient of around 50%. Agreement between the measures of autonomic nervous function varied greatly, between 0% and 87%. The HRV-power ratio measure and the blood pressure changes in the lyingto-standing test showed the lowest agreement with all other measures. Conclusion/Interpretation. This study provides agespecific and sex-specific reference values for a wide range of different autonomic function measures in an elderly population. Agreement among the different measures varied widely and reproducibility was only moderate. [Diabetologia (2003) 46:330-338] Keywords Aging, agreement, baroreflex, diabetes mellitus, heart-rate variability, nervous system, autonomic, reference values, reproducibility.

Van de Vooren H, Gademan MG, Swenne CA, TenVoorde BJ, Schalij MJ, Van der Wall EE. Baroreflex sensitivity, blood pressure buffering, and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients. J Appl Physiol 102: 1348 -1356, 2007. First published December 21, 2006; doi:10.1152/japplphysiol.00158.2006.-The arterial baroreflex buffers slow (Ͻ0.05 Hz) blood pressure (BP) fluctuations, mainly by controlling peripheral resistance. Baroreflex sensitivity (BRS), an important characteristic of baroreflex control, is often noninvasively assessed by relating heart rate (HR) fluctuations to BP fluctuations; more specifically, spectral BRS assessment techniques focus on the BP-to-HR transfer function around 0.1 Hz. Skepticism about the relevance of BRS to characterize baroreflex-mediated BP buffering is based on two considerations: 1) baroreflex-modulated peripheral vasomotor function is not necessarily related to baroreflex-HR transfer; and 2) although BP fluctuations around 0.1 Hz (Mayer waves) might be related to baroreflex BP buffering, they are merely a not-intended side effect of a closed-loop control system. To further investigate the relationship between BRS and baroreflex-mediated BP buffering, we set up a computer model of baroreflex BP control to simulate normal subjects and heart failure patients. Output variables for various randomly chosen combinations of feedback gains in the baroreflex arms were BP resonance, BP-buffering capacity, and BRS. Our results show that BP buffering and BP resonance are related expressions of baroreflex BP control and depend strongly on the sympathetic gain to the peripheral resistance. BRS is almost uniquely determined by the vagal baroreflex gain to the sinus node. In conclusion, BP buffering and BRS are unrelated unless coupled gains in all baroreflex limbs are assumed. Hence, the clinical benefit of a high BRS is most likely to be attributed to vagal effects on the heart instead of to effective BP buffering. autonomic nervous system; cardiovascular variability; Mayer waves; spectral analysis; transfer function IN DAILY LIFE, multiple processes perturb blood pressure. The duration of these challenges varies widely. For example, respiration makes blood pressure fluctuate with every breath (13), while physical or mental stress elevates blood pressure for minutes or even longer. The arterial baroreflex is a negativefeedback mechanism that effectively buffers such incidental blood pressure fluctuations (11,20,21,23). In negativefeedback systems, feedback delay often causes resonance in a given frequency band; this is the price to be paid for effective buffering at other frequencies. Resonance in blood pressure (5,8,12,31,49) manifests in the form of the well-known Mayer (22, 33) waves (beat-to-beat blood pressure oscillations with a frequency of ϳ0.1 Hz/period of ϳ10 s). Effective baroreflex blood pressure buffering occurs below the Mayer frequency (10, 16).Besides a sympathetic limb that modulates peripheral resistance, the baroreflex has ...