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Objective: To determine the predictive value of findings on continuous ambulatory electrocardiographic monitoring in elderly subjects. Design - Retrospective chohort study. Ten year follow up of randomly selected elderly subjects who participated in ambulatory electrocardiography study in 1982. Mortality data derived from offical registers. Setting: Turku, Finland. Subjects: 480 people aged 65 or older in 1982 who were living in the coummunity, of whom 72% agreed to participate. Main outcome measures: Mortality from cardiac and non-cardiac causes during 10 year follow up. Results: In the univariate analysis adjusted for age, risk of death from cardiac causes was increased among those with ventricular ectopy of more than 100 beats during the day (odds ratio 2.6; 99% confidence interval 1.4 to 6.1) or at night (3.3; 1.1 to 9.8) and in those with multifocal ventricular ectopic beats during the day (2.3; 1.0 to 5.0) or night (3.0; 1.3 to 7.1) compared with those with no ventricular ectopy. Sinoatrial paused exceeding 1.5 seconds during the day (4.5; 1.8 to 11.1) were also associated with excess mortality from cardiac causes. None of the findings on ambulatory electrocardiography predicted death from non- cardiac causes. A further study of explantory variables in the stepwise logistic regression analysis showed that sinoatrial pauses exceeding 1.5 seconds (4.0; 95% confidence interval 1.8 to 8.9) and night time multifoucal ventricualr ectopy (2.7; 1.2 to 5.9) predicted excess mortality from cardiac causes independently of age or clinically evident heart disease. Conclusion: Daytime sinoatrial pauses exceeding 1.5 secods and night time multifocal ventricular ectopy in the ambulatory electrocardiogram predict increased mortality form cardic causes independenlty of clinically evident cardiac diseases in unselected elderly subjects.

In order to study normal dynamic pupillary function and to determine reference limits for various pupillary variables, 81 healthy subjects aged between 32 and 60 years were examined using a portable infrared pupillometer. Additionally, 36 patients with type I diabetes mellitus were studied. In healthy subjects, sex had no, or only marginal, effect on the responses. Body mass index or smoking habits had no effect on pupillary dynamics. The relative reflex amplitude (RRA) was independent of age. The time to minimum diameter tmin was dependent on maximum constriction velocity (MCV) (P < 0.001) but not on age, initial diameter or reflex amplitude (RA). The MCV, maximum redilatation velocity (MRV) and time to 75% redilatation (t75%) were strongly dependent on RRA (P < 0.001 for each), but age had no or only a marginal effect. No correlation existed between the results of pupillometry and those of Valsalva or deep breathing tests. The lowest normal value for RRA was 29%. The reference limits for MCV, MRV and t75% were calculated in relation to RRA. The smaller the RRA was, the slower the velocities and the shorter the t75% were. Using these reference limits, 25% of the diabetic patients without cardiac autonomic neuropathy and 50% with definite cardiac autonomic neuropathy had abnormalities in at least one out of four pupillary variables. It is concluded that infrared pupillometry may be a useful additional method for the assessment of autonomic function.

Cardiovascular reflexes were studied in 22 healthy women before they were pregnant, once during each pregnancy trimester and after delivery to evaluate the effect of pregnancy on autonomic control of haemodynamics. The Valsalva manoeuvre, the deep breathing test, the orthostatic test and the isometric handgrip test were used to assess changes in autonomic nervous function. We found that pregnancy altered the heart rate response in the Valsalva manoeuvre, the deep breathing test and the orthostatic tests. The deep breathing difference (p = 0.03) and max/min ratio (p = 0.03) decreased in pregnancy, whereas standing heart rate increased (p < 0.0001). Both the systolic and diastolic blood pressure increased after standing up during pregnancy. The circulatory responses to isometric exercise were not affected by pregnancy. The results show that parasympathetic respon-siveness is decreased in pregnancy and that it returns to normal after delivery.

The effect of coronary artery bypass grafting (CABG) on standard cardiovascular reflex tests and pupillometry was studied in 15 patients with coronary artery disease without previous myocardial infarction. The heart rate responses to the deep breathing test and to the Valsalva manoeuvre were attenuated after CABG, whereas CABG had no effect on the beat-to-beat measured blood pressure responses (Finapres) or the pupillometric variables. Although the heart rate responses diminished in almost all of the patients after CABG, the values, however, remained in most cases within the age-related normal range. It is concluded that the attenuation of heart rate responses after CABG is due to perioperative local damage on the effector organ or autonomic nerves rather than due to dysfunction on the baroreceptor level or in cranial level of the autonomic nervous system. Because the blood pressure responses were not affected by CABG and the heart rate responses after CABG mainly remained within the normal range indicating sufficient parasynthetic activity, it is probable that the clinical significance of the effects of CABG on the autonomic nervous system is not very important.

To study the usefulness of standard cardiovascular autonomic reflex tests in the elderly, 224 healthy controls and 49 aged diabetic patients were examined. Based on the data obtained from healthy controls, age-related reference values for several autonomic indices were calculated and their usefulness was tested with aged diabetic patients. It was found (1) that in elderly subjects (aged > or = 50 years) the indices based on heart rate differences are more suitable for the assessment the autonomic parasympathetic control than indices based on R/R interval ratios, (2) that the tests (and indices) of choice in the elderly subjects are the Valsalva manoeuvre (Valsalva difference and tachycardia difference) and the active orthostatic test (Max-Rest difference, immediate and later change in systolic blood pressure), (3) that the usefulness of the deep breathing test is limited in the elderly, (4) that such commonly used indices as the Valsalva ratio and the Max/Min ratio in orthostatic test are not useful in the elderly, and (5) that the isometric handgrip test is of little use in the assessment of the autonomic function in the elderly. In conclusion, standard cardiovascular autonomic reflex tests can be used in the assessment of autonomic function to some extent also in the elderly subjects. However, one must bear in mind the limitations in their applicability in that age group.

Objective To study the physiological responses to noninvasive cardiovascular autonomic function tests in normal pregnancy. Design Cardiovascular autonomic responses in 60 women at 22 to 29 weeks gestation and 62 nonpregnant women were investigated using the Valsalva manoeuvre as well as orthostatic, quiet breathing, deep breathing, and isometric handgrip tests. Results Compared with nonpregnant women, those who were pregnant showed significantly lower heart rate variability during normal breathing and a blunted tachycardic reaction to blowing during the Valsalva manoeuvre. The vagally controlled biphasic heart rate response to standing was also attenuated in the pregnant group. Conclusions The cardiovascular responses were blunted in mid-pregnancy indicating a decrease in parasympathetic cardiovascular control.

The results of cardiovascular autonomic reflex tests on 224 healthy, randomly selected subjects were analysed to study possible sex differences in the autonomic responses. The heart rate response to the Valsalva manoeuvre (Valsalva ratio) was greater in females over 50 years than in males of the same age (1.58 +/- 0.34 vs. 1.44 +/- 0.30, p0.05). The heart rate response to deep breathing (E/I ratio) was higher in females under 50 years than in males under 50 years (1.37 +/- 0.17 vs. 1.34 +/- 0.18, p0.001). The diastolic blood pressure response to isometric handgrip was higher in males under 50 years than in females of the same age (p0.05). Although there were sex differences in the magnitude of the responses, the effect of age was similar in males and females and accelerated attenuation of the autonomic responses could not be demonstrated with increasing age. It can be concluded that significant sex differences exist in cardiovascular autonomic responses. The implication of such differences need consideration.

In order to study the association between warm thermal-perception thresholds (WPT), cold thermal-perception thresholds (CPT) and cardiovascular autonomic function, we examined 91 otherwise healthy patients with diabetes mellitus (69 with type I and 22 with type II). The covariance analysis revealed that WPT was associated with the deep-breathing EI ratio and the Valsalva ratio ( p = 0.004 and p = 0.008, respectively) whereas CPT was associated with the Valsalva ratio and the postural blood pressure decrement ( p = 0.008 and p = 0.004, respectively). These associations possibly reflect histological similarities between the parasympathetic nerves and those mediating warm sensation, and between the sympathetic nerves and those mediating cold sensation.

The association of disease duration with deterioration of cardiovascular autonomic reflexes was studied in two groups of young patients with insulin-dependent diabetes mellitus (IDDM). The mean age of the patients in both groups was 31 years and the mean duration of the disease was 3 (n = 18) and 16 (n = 22) years. No significant difference in group means was seen in the test parameters of autonomic nerve function. However, five patients with long-term disease, but none with short-term disease, had test scores indicating cardiac autonomic neuropathy. It was concluded that (1) the duration of the disease has no overall effect on autonomic nerve function in young patients with IDDM, but (2) a few individuals with IDDM may have some precipitating factors leading to autonomic neuropathy in the course of the disease.

Possible effects of environmental stress-induced elevation of the heart rate on the magnitude of cardiovascular autonomic responses were studied in 123 healthy subjects. The nocturnal heart rate was evaluated using ambulatory 24-h ECG monitoring. Some of the cardiovascular responses were found to be significantly weaker in those subjects whose resting heart rate during testing was greater than 10 beats min-1 higher than the resting nocturnal heart rate. It is thus highly important to minimize the environmental disturbances during autonomic testing.

The purpose of this study was to investigate the effect of the beta-adrenergic antagonist, propranolol, on the nocturnal masseter muscle activity of a heavy sleep bruxist. Three all-night polysomnographic registrations were performed with bilateral masseter muscle EMG recordings. The first night study served as the baseline night, the second night registration was performed after total sleep deprivation and the third night registration was made with propranolol. Sleep deprivation decreased the masseter contraction (MC) index by 61% and propranolol by 72% when compared to the level of the baseline night. This preliminary observation is in line with our hypothesis suggesting a link between autonomic regulation of circulation and rhythmic activation of masticatory muscles, especially when associated with body movements during sleep.

To examine the hypothesis of disturbed autonomic function, non-invasive cardiovascular reflex tests were performed on 11 sleep bruxists in the waking state. The tests included the Valsalva manoeuvre, a deep-breathing test, and an orthostatic test (standing up). The R-R intervals were monitored continuously, and blood pressure was measured non-invasively and continuously using the Finapres method. In total, 64% of bruxists showed abnormalities in at least two variables reflecting the cardiovascular autonomic function. Abnormalities were found in blood pressure regulation during the Valsalva strain, and in the immediate biphasic heart rate response during standing up, but not in the vagally mediated deep-breathing difference. These findings suggest that bruxism is accompanied by abnormalities in autonomic function, particularly in sympathetic vasoconstrictor function.

To assess normal autonomic haemodynamic responses to the Valsalva manoeuvre, 158 healthy unmedicated subjects, aged 25-60 years, were examined. For measurement of beat-to-beat blood pressure on a finger, the Finapres instrument was used. Phase-to-phase changes in instantaneous blood pressure and heart rate and the latency response between the end of a Valsalva manoeuvre and points on the resultant blood pressure and heart rate were calculated, and the reference limits for various indices were determined. Sex had no or only marginal effect on blood pressure or heart rate responses or latencies. Ageing was accompanied by a smaller decrease and smaller partial recovery of blood pressure during the strain, with attenuation of reflectory bradycardia, and lengthening of the latencies. It is concluded that age-related reference values should be applied in the interpretation of the Valsalva responses. The following responses should be analysed: mean blood pressure decrease and partial recovery during the strain (adrenergic vasoconstrictor function), reflectory bradycardia after the strain (parasympathetic function), and the latencies (sympathetic and parasympathetic function).

The effect of the resting heart rate on heart rate responses in standard cardiovascular autonomic function tests was studied in a sample of 845 subjects. The responses, which were calculated using instantaneous heart rate changes and R—R interval ratios, were divided into quantiles according to their absolute values. The effect of resting heart rate on each cardiovascular index was studied by linear regression analysis, first in the whole group and then in the group with responses belonging to the lowest quantile. As regards the whole group, eight out of ten indices diminished significantly with increasing resting heart rate. However, no response-attenuating effect of increasing resting heart rate could be found among the responses in the lowest quantile. Since particularly low heart rate responses in cardiovascular reflex testing are of clinical importance when autonomic neuropathy is diagnosed, it can be concluded that the usefulness of standard cardiovascular reflex test based on heart rate changes is not limited by the level of the resting heart rate.

In order to study influence of moderate obesity on autonomic nervous function, nineteen identical twin pairs were studied by standard non-invasive cardiovascular reflex tests and pupillometry. There had to be a difference in Body Mass Index (BMI) of at least 3 kg/m2 between the twins. The mean +/- s.d. BMI was 30 +/- 2 and 23 +/- 1 kg/m2 in obese and non-obese individuals, respectively. All of the participants were healthy and they did not use any drugs known to affect autonomic function. No significant differences were found in any of the heart rate, blood pressure, or pupillary responses between obese and non-obese twins. A strong correlation between lean and obese pairs was found in most autonomic variables reflecting parasympathetic function and in some reflecting sympathetic function. It is concluded that (1) neither sympathetic nor parasympathetic responsiveness is affected significantly by moderate obesity and (2) genetic factors play an essential role in determining the cardiovascular autonomic reactivity.

The effect of acute dose of caffeine (4 mg kg-1) on cardiovascular autonomic responses were studied in 10 healthy subjects. Standard cardiovascular reflex tests were used during which heart rate and blood pressure were continuously measured. Each subject was tested twice in a random order, with and without prior use of caffeine. It was found that immediate heart rate responses following standing up were lower under influence of caffeine. Blood pressures were systematically, although non-significantly, higher and blood pressure responses in isometric handgrip test stronger when caffeine was used before testing. It is suggested that caffeine should not be used before autonomic testing. This is especially important when the test(s) are performed for research purposes or in order to study the blood pressure responses. If the tests are made for diagnostic purposes the following rules should be adopted: (1) if the subject has used caffeine before testing but all heart rate responses are within normal ranges, it can be assumed that the subject does not have cardiac parasympathetic neuropathy and retesting is not necessary: (2) if the patient has used caffeine before testing and the results suggest presence of autonomic neuropathy, the patient must be retested without the prior use of caffeine.

In order to study the effect of smoking on cardiovascular function, 25 healthy subjects with an average smoking history of 25 ± 9 pack-years were examined using the Valsalva manoeuvre and the deep-breathing test. For each smoker there was a healthy, non-smoking control subject of matching age, sex and body mass index. During the tests, heart rate and blood pressure were recorded continuously. Compared with the controls, the smokers had (1) a smaller increase in heart rate during the strain phase of the Valsalva manoeuvre (P = 0.04); (2) weaker rebound increases in arterial pressure after the Valsalva strain (P = 0.007 for systolic and P = 0.02 for diastolic blood pressure); (3) smaller reflex bradycardia after the Valsalva strain (P = 0.02); and (4) a longer latency between post-strain rises in pressure and bradycardia (P = 0.001). This suggests that diminished blood pressure responses occur as a consequence a chronic dysregulation of peripheral vasoconstriction, while diminished heart rate responses are due to attenuated blood pressure responses. A prolonged latency may be a sign of a dysfunction of parasympathetic baroreflex control. It is concluded that heavy smoking is accompanied by a disturbance of cardiovascular autonomic control.

To assess the possible dysrhythmogenic effect of cardiovascular autonomic function tests, ECG tracings of 925 consecutive subjects, taken during a battery of cardiovascular autonomic reflex tests were analyzed. The battery included the Valsalva manoeuvre, deep breathing test, orthostatic and isometric handgrip. The frequency of ventricular extrasystoles increased during or after the tests, compared with the resting phase, in 11% of healthy subjects, in 11% of diabetic subjects and in 23% of subjects with a previous myocardial infarction (p = 0.001 vs healthy subjects). In patients with previous myocardial infarction, the most dysrhythmogenic individual tests were orthostatic and isometric handgrip. In nine subjects, other cardiac rhythm disturbances were detected (including nonsustained ventricular tachycardia, conduction block, and atrial fibrillation). In all cases, the dysrhythmias were asymptomatic and resolved without medical intervention. In conclusion, we consider the cardiovascular reflex test battery safe for the patient. However, due to occasional potentially significant dysrhythmias we recommend continuous monitoring of the electrocardiogram and immediate access to resuscitation facilities during cardiovascular autonomic testing.

Thirty-four patients with RA, 76 diabetic subjects (DM) and 67 healthy controls (CR) were studied in order to study cardiovascular autonomic function in RA. Valsalva manoeuvre, deep breathing test and active orthostatic test were used. Resting heart rate (resting HR) was markedly elevated in the RA and DM groups. Therefore, the groups were compared using analysis of variance with age and resting HR as covariates. The analyses showed no differences in cardiovascular responses between the RA group and CR group but cardiovascular responses were significantly diminished in the DM group compared with both the CR group and RA group. Our data indicate that the parasympathetic efferent pathway mediating cardiovascular reflexes via the nervus vagus is intact in RA. Thus elevated resting HR in RA does not seem to be due to peripheral parasympathetic damage. Physical deconditioning may explain the elevation of resting HR in patients with RA.

Summary. The effects of smoking habits on aotnomic cardiovascular heart rate reflexes were studied in 143 healthy subjects by using the Valsalva manoeuvre and deep breathing tests. Smoking seemed to cause attenuation of the Valsalva heart rate response. This attenuation was present also after adjustment for possible confounding factors including alcohol consumption. Our findings show that in subjects with smoking history there may occur dysfunction in some part of the autonomic reflex arch mediating the Valsalva heart rate response.

Summary. Spectral analysis of heart rate variability was used to study autonomic nervous control in mid-pregnancy. Fifty women (age 22–36 years) with singleton pregnancies (mean duration of gestation 27.7 weeks) and 39 non-pregnant female controls (age 21–39 years) were studied using controlled breathing and orthostatic tests. During spontaneous breathing the overall heart rate variability was lower in pregnant subjects indicating a decreased parasympathetic tone at rest. The decreased parasympathetic tone probably counts for the increased heart rate in pregnancy. The parasympathetic efferent capacity of autonomic cardiac control was found to be similar in pregnant and non-pregnant subjects, as no difference was seen during controlled breathing in periodic heart rate variability between the groups. Standing up caused a similar change in low frequency and mid-frequency bands in both groups, but high frequency heart rate variability increased in pregnant subjects and decreased in the controls indicating an increased sympathetic tone at rest in mid-pregnancy.

Eighty-five subjects, aged 31-55 years, suffering from uncomplicated essential hypertension and receiving no regular medication were randomized to sodium restriction and control groups. Systolic (SBP) and diastolic (DBP) blood pressure were measured during an orthostatic test at baseline and after 6 months sodium restriction. The mean daily sodium excretion of 43 treated subjects decreased from 193 +/- 91 mmol to 95 +/- 70 mmol (p less than 0.001). Treated patients were divided on the basis of their mean overall out-patient clinic (OC) DBP decrease in the sitting position during the 6 months (monthly measurements) into sodium-sensitive (DBP decrease greater than 10 mmHg, n = 17), indeterminate (DBP decrease 5-10 mmHg, n = 18) and sodium-resistant (DBP decrease less than 5 mmHg, n = 8) subgroups. At 6 months the level of DBP in the supine position was lower than at baseline in both sensitive and resistant subgroups, whereas in the standing position a lower DBP than at baseline was seen only in the sodium-sensitive subgroup. The magnitude of the subsequent OC DBP decrease was significantly associated with a high baseline seated OC DBP (p less than 0.001) and a high, for baseline OC DBP adjusted orthostatic DBP increase (p = 0.014). Our data suggest that posture should be included in the concept of sodium sensitivity and that an orthostatic test is useful in the prediction of seated and standing DBP decrease produced by moderate, long-term sodium restriction.

Observations on 1,282 measurements of non-invasive cardiovascular reflex testing of autonomic function in 1,023 control subjects and patients with different disorders are presented. It is suggested that the Valsalva manoeuvre be performed three times rather than once and the highest Valsalva ratio should be used instead of the mean or first of the three ratios. The deep breathing test gives equally reliable information when three breathing cycles are used instead of six. Symptoms were detected in up to 15% of the subjects depending on the test, although the majority of these were minor and transient. The frequency of ventricular/supraventricular extrasystoles increased especially during the Valsalva manoeuvre (+67%/+40%) and post-strain (+49%/+25%) phases and early recovery phase of the orthostatic test (+69%/+156%) and to a lesser degree during deep breathing (+18%/+50%) and handgrip (+36%/-11%) phases compared with the resting phase. However, severe cardiac rhythm disturbances were very rare. 1-2% of the younger (less than 50 years) and 10% of the older subjects were not able to perform the tests adequately. The R-R intervals on which the results are based should be selected carefully, and use of a continuous non-invasive method of blood pressure monitoring should provide further useful information.

Ten healthy normal subjects participated in a follow-up study in which the reproducibility of noninvasive cardiovascular autonomic function testing was studied. The tests used were the Valsalva manoeuvre, deep and quiet breathing, standing upright and isometric handgrip exercise. These tests were performed six times within a 2-year period. The reproducibility of these autonomic function tests within a day was evaluated in a separate study involving nine healthy subjects. In this study the tests were performed three times between 08.00 and 15.00. The results indicate that indices based on R-R interval ratios during testing were highly reproducible; that the indices remain reproducible over a 2-year follow up period and that reproducibility within a day was similar to that within longer time periods. The reproducibility of pressor responses to isometric exercise was poor. It is concluded that indices based on R-R ratios are suitable for use in follow up studies of autonomic function.