Risk factors for mortality of medical causes within 30 days of electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is used to treat severe psychiatric disorders and is associated with reduced risk of suicide and all-cause mortality in patients with severe depression. We investigated the causes of death occurring shortly after ECT and identified potential risk factors for medical causes of death. METHODS: Patients treated with ECT between 2012 and 2018 were included in this Swedish register-based study. Multivariate binary logistic regression was used to calculate odds ratios for covariates to determine potential predictors of 30-day mortality. RESULTS: Of the 20,225 included patients, 93 (0.46 %) died of suicide and 123 (0.61 %) died of medical causes after ECT. Cardiovascular disease was the most common medical cause of death (n = 49, 40 %). An older age, a Charlson Comorbidity Index of 1 or more, atrial fibrillation, kidney disease, reflux disease, dementia, and cancer were associated with increased risk of death by medical causes. LIMITATIONS: Real-life observational studies based on registry data may demonstrate associations, but cannot determine causality. If medical records had been available, we would be better able to determine if deaths were due to the ECT, anesthesia, pre-existing medical conditions, or the mental disorder. CONCLUSIONS: ECT appears to be a low-risk medical procedure. Older individuals with severe somatic diseases have the highest risk of death and extra measures should be considered to optimize their medical health during the pre-ECT workup, and during and after ECT.

Automatic computerized analysis of heart rate variability with digital filtering of ectopic beats.

Analysis of heart rate variability (HRV) has been used in studies of autonomic function and risk assessment in different patient groups such as in patients with diabetes mellitus, after myocardial infarction (MI) and other cardiovascular disease. Ectopic beats can, however, interfere with HRV analysis and give erroneous results. We have therefore studied the impact of ectopic beats on HRV analysis and the ability of a filter algorithm to correct this. Power spectral analysis of synthetic data with an increasing proportion of ectopic beats and 24-h Holter recordings from 98 healthy subjects and 93 post MI patients was done with and without digital filtering and interpolation of errors in the data stream. The analysis of HRV was seriously hampered by less than 1% of ectopic beats. A filter algorithm based on detection and linear interpolation of ectopic beats and other noise in the data stream corrected effectively for this in the synthetic data employed. In the healthy subjects and the post MI patients, filtering markedly reduced the extra variability related to non-normal beats. The software could automatically analyse over one hundred 24-h files in one batch. HRV analysis should include filtering for ectopic beats even with a small number of such beats. It is possible to make a fast analysis automatically even in huge clinical series, which makes it possible to use the method both clinically and in epidemiological studies.

Blood pressure and cardiovascular autonomic function in healthy children and adolescents.

OBJECTIVES: To investigate the relationship between blood pressure levels and cardiovascular autonomic function in adolescents and preadolescents. STUDY DESIGN: We measured variability of beat-to-beat arterial pressure and R-R intervals using power spectral analysis in 56 adolescents (aged 13-16 years; mean age, 9.0 +/- 1.4 years) and 71 preadolescents (6-12 years; mean age, 13.5 +/- 1.1 years) in the supine and standing positions. RESULTS: Adolescents had higher levels of systolic arterial pressure and lower high-frequency power of RR intervals than preadolescents. Correlation between the basal level of arterial pressure and autonomic function was observed in adolescents but not in preadolescents. In adolescents, multivariate analysis indicated that the basal level of arterial pressure was inversely related with the high-frequency power of RR intervals and positively with the ratio of low-frequency and high-frequency power. No significant relation was found in preadolescents. During standing, adolescents had a more marked increase in diastolic arterial pressure, heart rate, low frequency of R-R intervals, and low frequency of arterial pressure compared with those of preadolescents. Changes in diastolic pressure showed a significant negative correlation with changes in high frequency of R-R intervals. CONCLUSION: Cardiovascular autonomic function plays an important role in increasing blood pressure levels associated with increased modulation of vagal tone of the heart after puberty but does not in the preadolescent.

Autonomic neuropathy--a complication less pronounced in patients with Type 1 diabetes mellitus who have lower blood glucose levels.

AIMS: Autonomic neuropathy is a serious diabetic complication, probably contributing to the death of many young people with Type 1 diabetes mellitus. It is often not diagnosed. METHODS: Patients with Type 1 diabetes from the Stockholm Diabetes Intervention Study were investigated with power spectral analysis (n = 88), heart rate and blood pressure reactions to tilting (n = 66), and heart rate variability during deep breathing (n = 70) a mean of 11.4 years after randomization to intensified conventional treatment (ICT) or standard treatment (ST), the treatment groups similar with regard to age, duration of diabetes and metabolic control at baseline (HbA1c 9.4 (1.3)%, mean (SD)). Blood glucose levels (mean of 29 HbA1c values) during the 10 years were lower in the patients from the ICT group (7.2 (0.6) vs. 8.3 (1.0)%, P = 0.001). RESULTS: Heart rate variability (HRV) in the high frequency range (P = 0.034), the expiration-inspiration ratio (P = 0.020), and the brake index during tilt (P = 0.044) were lower in the ST group, indicating more pronounced parasympathetic insufficiency. Systolic blood pressure fell by 10 (16) mmHg in the ST group, and by 2.5 (15) mmHg in the ICT group 8 min after rising from the supine to a 70 degrees upright position (P = 0.034). A decreased autonomic function was associated with age and higher HbA1c. CONCLUSION: Better autonomic nerve function is associated with lower HbA1c and lower age which were both the same in the intensively and the conventionally treatment groups at baseline. After a mean of 11.4 years autonomic function was better in the intensively treated group.

24-hour ECG frequency-domain measures in preeclamptic and healthy pregnant women during and after pregnancy.

OBJECTIVE: The aim of the present study was to evaluate the autonomic balance in women with preeclampsia and in healthy women during and after pregnancy by means of a 24-h ECG Holter recording combined with power spectral analysis. METHODS: Fifteen preeclamptic and 15 healthy women underwent 24-h Holter monitoring in the 32nd-36th week of gestation and 3-6 months postpartum. The power spectrum of the maternal electrocardiogram was analyzed with an autoregressive algorithm. MAIN OUTCOME MEASURES: The power spectrum contains two major components: a low-frequency peak, primarily attributed to sympathetic tone, and a high-frequency peak, reflecting vagal tone. RESULTS: The power spectrum of maternal heart rate variability did not differ between preeclamptic and normal women during pregnancy. After delivery, the amplitude of all components became significantly higher than those during pregnancy, with one exception: the high-frequency component in the patients who had been preeclamptic. In a comparison of the two groups, the high-frequency component after delivery was significantly lower in women who had preeclampsia than in normal healthy women (p = 0.03). CONCLUSIONS: During pregnancy, the power spectrum is reduced and cannot be used to distinguish between patients with preeclampsia and normal healthy women. Three to 6 months after delivery, the high-frequency component is still reduced in the preeclamptic group of women. This indicates an impaired vagal modulation even in the nonpregnant state in this group of women, unlike those who had a normotensive pregnancy.

Autonomic function in children with type 1 diabetes mellitus.

We investigated autonomic function in 58 children and young adults with Type 1 diabetes mellitus (aged 7-22 years, duration from 3 to 18, 8.6 +/- 3.4 years) and in 74 healthy controls (6-21 years) using power spectral analysis of blood pressure and heart rate in addition to conventional standard autonomic function tests: deep breathing, the Valsalva manoeuvre, and a standing test. None of the diabetic patients were symptomatic. Reproducibility of the tests was assessed by determining the coefficient of variation in 9 controls (7.8-37.7%). Thirteen per cent of the subjects had difficulty in adequately performing the Valsalva manoeuvre. After adjustment for age, sex, body mass index, and respiratory frequency, results of the Valsalva manoeuvre and deep breathing were not different between patients and controls and there was no significant postural reduction in systolic blood pressure (> or = 20 mmHg) in the patients. Heart rate variation in the supine position during natural breathing was low in patients, although power spectral analysis of heart rate variation did not show a significant decrease in the power density in the high and the low frequency in patients compared to healthy controls. Beat-to-beat blood pressure fluctuation was significantly lower in patients and correlated with metabolic control (mean annual haemoglobin A1c), but not with disease duration and was abnormal in 7 diabetic children (12%). In contrast, tests of vagal activity were not impaired in the patients in this age range. We concluded that vagal involvement in Type 1 diabetic patients determined by spectral analysis of R-R intervals in addition to conventional tests is uncommon, but that beat-to-beat blood pressure variation was more likely to be affected.

Heart rate variability in patients with epilepsy.

Autonomic function was studied by the use of spectral analysis of heart-rate variability in patients with epilepsy in relation to type of epilepsy and anti-epileptic drug therapy. A total of 21 patients with juvenile myoclonic epilepsy (JME) and 21 with temporal lobe epilepsy (TLE) were included; 18 patients were treated with carbamazepine (CBZ), 16 with valproate (VPA) and seven with phenytoin (PHT). One healthy drug free control, matched for age and sex, was selected for each patient. Patients and controls underwent an ambulatory 24 h EKG. Heart-rate variability was analyzed in time and frequency domains. Patients with TLE had significantly lower S.D. of the RR-intervals, lower low frequency power and a lower low frequency/high frequency power ratio than their controls. A lower low frequency/high frequency power ratio was the only significant difference between the JME patient group and their controls. Treatment, however, may have had a considerable influence on the heart rate variability in the epilepsy patients. Patients on CBZ had significantly lower S.D. of RR-intervals, low frequency power and a low frequency/ high frequency power ratio than did their matched healthy drug free controls. The ratio of low frequency/high frequency power was also lower in patients on VPA compared with their controls, but apart from that no differences could be demonstrated between this treatment group and the controls. In conclusion, patients with epilepsy appear to have an altered autonomic control of the heart, with a reduction in some heart-rate variability measures, suggesting a decreased sympathetic tone, which may be related to the drug therapy or the epilepsy as such. Further studies are warranted to explore these changes and their possible relevance for sudden death in epilepsy.

Habitual snorers and sleep apnoics have abnormal vascular reactions of the soft palatal mucosa on afferent nerve stimulation.

A local disturbance in the afferent nerves involved in the reflexogenic dilation of the upper airways (UAs) could contribute to the increased collapsibility seen in patients with obstructive sleep apnea (OSA). Laser Doppler perfusion monitoring, combined with electrical stimulation, is a method for investigating the afferent nerve regulation of the microcirculation. It was used in the mucosa of the soft palate in 35 patients with various degrees of UA obstruction and in 13 control subjects, all nonsmoking men. In a majority of snorers and patients with mild OSA, stimulation induced an exaggerated vasodilation, compared with controls. In contrast, in patients with severe OSA, the vasodilation was significantly reduced, compared with controls. These signs of disturbances in the microcirculation support the hypothesis of a local progressive afferent nerve lesion in heavy snorers with or without OSA.

Ultrasound-Doppler technique for monitoring blood flow in the brachial artery compared with occlusion plethysmography of the forearm.

Blood flow changes in the brachial artery of seven subjects during and after submaximal static handgrip contractions were measured by duplex Doppler ultrasound technique. These measurements were compared with the results of occlusion plethysmography, measured immediately (2-3 heartbeats) after. For the combined data from all measurements, a common calibration line could be drawn (linear regression, r=0.92). The flow measurements from the two methods were tested by a four-way analysis of variance and there was no significant difference between the methods during (static) exercise, indicating acceptable coherence. Occlusion plethysmography may well be used for monitoring forearm blood flow during conditions of static exercise. In addition, the cuff occlusion pressure of the plethysmograph (50 mmHg) decreased the blood flow of the brachial artery by approximately 28% as measured by duplex Doppler ultrasound.

Heart rate variability in healthy subjects is related to age and gender.

The effects of age and gender on heart rate variability as measured by spectral and time domain analysis of 24 h ECG recordings were evaluated in 101 healthy subjects, 49 men and 52 women (20-69 years of age). In the frequency domain, total power, very low-frequency power, low-frequency power and high-frequency power were negatively correlated to age (P < 0.001 for all variables). Total power decreased by 30% between 20-29 and 60-69 years of age. In the time domain, SDNN-index, the mean of the standard deviations of all normal R-R intervals for all 5 min segments of a 24 h ECG recording, was negatively correlated to age (P < 0.001). Total power, very low-frequency power, low-frequency power and the low-frequency/high-frequency ratio were lower in women (P < 0.05, P < 0.05, P < 0.01 and P < 0.01), although the absolute differences were much smaller than for age. There was a pronounced circadian variation; at night total power increased in all age groups (P < 0.01). The results show that age, and to a lesser degree gender, are important determinants of heart rate variability in healthy subjects. Heart rate variability is a valuable tool for risk stratification in cardiovascular disease, but the physiological effects of ageing, with diminishing heart rate variability in older age groups, must also be taken into account.

Markers of risk after acute myocardial infarction. A comparison of clinical variables, ambulatory and exercise electrocardiography, echocardiography, and stress echocardiography.

BACKGROUND: Short-term mortality after myocardial infarction has decreased continuously among members of selected populations. Nonetheless, the long-term prognosis among members of unselected populations remains bad. Further research in risk stratification is therefore needed. In the present study we tested the additive value of clinical variables, echocadiography, ambulatory electrocardiography, exercise testing, and stress echocardiography in assessing the long-term prognosis after acute myocardial infarction. METHODS: Two-dimensional echocardiography and ambulatory electrocardiography (analysis of ST-segment changes and of heart rate variability) were performed for 74 patients aged < 75 years who had had an acute myocardial infarction. Before their discharge from hospital, 70 patients were subjected to a combined exercise test and stress echocardiography. The time of follow-up was > or = 3 years. RESULTS: During follow-up 18 patients died, and 38 suffered cardiac events defined as death, nonfatal reinfarction and the need for revascularization. We first tested 31 covariates in a univariate regression analysis. A subsequent multivariate analysis was performed in two stages. During the first of these, clinical variables (a history of systemic hypertension, infarct localization, and diabetes mellitus) and variables derived from noninvasive tests (new-onset wall-motion abnormality during stress echocardiography, ST-segment depression and heart-rate variability during ambulatory electrocardiography, the ejection fraction by echocardiography at rest, and the double product during exercise tests) predicted mortality. After the second stage, however, the only remaining independent predictors of mortality were the presence of a new-onset wall-motion abnormality (P < 0.0001, relative risk 13.5, 95% confidence interval 3.6-51.3), ST-segment depression during ambulatory electrocardiography (P = 0.003, relative risk 5.0, 95% confidence interval 1.7-15.7) and a decreased heart rate variability (P = 0.007). CONCLUSIONS: The only variables that were of independent value in assessing the long-term mortality were those expressing residual myocardial ischemia and the cardiovascular sympatho-vagal balance. It is, therefore, recommended that one should monitor these variables for patients recovering from an acute myocardial infarction.

Heart rate variability as a means of assessing prognosis after acute myocardial infarction. A 3-year follow-up study.

AIMS: The present study evaluated the prognostic value of heart rate variability after acute myocardial infarction in comparison with other known risk factors. The cut-off points that maximized the hazards ratio were also explored. PATIENTS AND METHODS: Heart rate variability was assessed with 24 h ambulatory electrocardiography in 74 patients with acute myocardial infarction, 4 +/- 2 days after hospital admission and in 24 healthy controls. Patients were followed for 36 +/- 15 months. RESULTS: During follow-up, 18 patients died, nine suffered a non-fatal infarction and 20 underwent revascularization procedures. Heart rate variability was higher in survivors than in non-survivors (P = 0.005). This difference was found at higher statistical levels when comparing non-survivors vs controls (P = 0.0002). A similar statistically significant difference was also found between survivors vs controls (P = 0.04). Patients suffering non-fatal infarction and cardiac events (defined as death, non-fatal infarction or revascularization) had a lower heart rate variability than those without (P = 0.03 and P = 0.03, respectively). With multivariate regression analysis, decreased heart rate variability independently predicted mortality and death or non-fatal infarction. The presence of a left ventricular ejection fraction < 40% and a history of systemic hypertension were, however, stronger predictors. The cut-off points that maximized the hazards ratio using the Cox model differed from those reported by others. CONCLUSION: Decreased heart rate variability independently predicted poor prognosis after myocardial infarction. However, the cut-off points that should be used in clinical practice are still a matter for further investigation.

Telephone help line for cancer counseling and cancer information.

PURPOSE: A telephone help line for providing cancer counseling and information was started in 1990 at the University Hospital of Uppsala, Sweden. The current study aimed to assess the experience of the telephone help line after 3 years of operation and to compare the results with telephone services in other countries. DESCRIPTION OF STUDY: For each telephone call, a standard report form was completed and a short narrative description of the caller's concerns was written. RESULTS: During the first 3 years, 735 calls were registered. Most of the calls were made by next of kin (30%) and patients (28%). Most (77%) of callers were women. The issues addressed were mainly medical or psychosocial. The medical questions were, in most cases, related to a patient's illness or treatment. The psychosocial questions dealt with the caller's (patient or next of kin) own anxiety, and these calls developed into supportive dialogues. Patients made more medical inquiries than next of kin, whereas family members were more concerned with psychosocial questions (P < 0.01). Questions relating to breast cancer accounted for a great part of the calls from patients (34%), but significantly less from the relatives (10%; P < 0.0001), whereas the opposite was true for colorectal adenocarcinomas (P < 0.01). These findings are discussed together with cultural differences between Sweden and other countries, particularly the United States. CLINICAL IMPLICATIONS: The telephone help line can supply information to patients, next of kin, and the general public on their own premises. Another important task is to function as a link between people with symptoms and appropriate health service.

Early atherosclerosis is retarded by improved long-term blood glucose control in patients with IDDM.

Microangiopathy is retarded by improved blood glucose control in patients with IDDM. Whether or not this is true for macroangiopathy (atherosclerosis) has remained unclear. A total of 59 patients (44 +/- 1.5 years, previous HbA1C 9.4 +/- 0.2%, mean +/- SE) with IDDM were investigated. Of the 59 patients, 31 had been randomized to long-term intensified conventional insulin treatment (ICT), and the remaining 28 had received standard insulin treatment (ST). Blood glucose control was significantly better in the ICT patients with an HbAlc value (mean of 29 values during 10 years) of 7.1 +/- 0.1% compared with the ST patients' 8.2 +/- 0.2% (P < 0.0001). With high-frequency ultrasound, endothelial function was measured as flow-mediated dilation of the right brachial artery. The carotid arteries were scanned for plaques, intima-media thickness was measured, and arterial wall stiffness was calculated in the right common carotid artery. These measurements correlate with manifest and/or risk factors for coronary atherosclerosis. The patients in the ST group had stiffer arteries (P = 0.011) and thicker intima-media in the left common carotid artery (P = 0.009) than those in the ICT group. Patients with lower HbA1c generally had better endothelial function (P = 0.028) and less stiff arteries (P = 0.009). Better blood glucose control in patients with IDDM is related not only to less microangiopathy but also to a slower development of atherosclerosis.

Autonomic cardiovascular control in normal and pre-eclamptic pregnancy.

BACKGROUND: Pre-eclampsia is regarded as a primary placental disorder, in which defect placentation causes endothelial and cardiovascular disturbances. Evidence of disturbed neural cardiovascular control in this condition has been suggested, as well as in other hypertensive diseases. The purpose of the present study was to non-invasively evaluate the sympathovagal balance during normal and pre-eclamptic pregnancy. METHODS: In twelve healthy pregnant women, thirteen pre-eclamptic women and ten nonpregnant controls, heart rate, blood pressure and breathing movements were registered and recorded on a tape recorder for off-line analysis. Variability in heart rate, blood pressure and breathing movements were computed by an autoregressive spectral analysis algorithm. Heart rate variability was quantitated as the area under the spectral curve, and Student's t-test was performed on logarithmic values. RESULTS: Heart rate variability contained two major components in power, a low frequency peak predominantly attributed to sympathetic tone, and a high frequency peak reflecting vagal tone. Women with pre-eclampsia were characterized by a significantly reduced high frequency peak compared to healthy pregnant (p = 0.03) and non-pregnant (p = 0.02) women. In the low frequency band there were no significant differences in power between the groups. Blood pressure variability did not differ between the groups. CONCLUSIONS: The present results indicate that pre-eclampsia is associated with decreased vagal control of the heart. Furthermore, the results indicate that pregnancy per se does not change sympatho-vagal balance.

Noninvasive test of microvascular endothelial function in normal and hypertensive pregnancies.

OBJECTIVE: To examine microvascular endothelial cell function in vivo in pre-eclampsia. DESIGN: Iontophoresis of acetylcholine (Ach), which gives rise to endothelial cell dependent vasodilatation, and of sodium nitroprusside (SNP), which elicits vasodilatation independently of functioning vascular endothelium. SETTING: Södersjukhuset, Stockholm, Sweden. SUBJECTS: Ten pre-eclamptic patients, ten healthy pregnant women and ten healthy nonpregnant women were examined. MAIN OUTCOME MEASURES: The degree of vasodilatation following iontophoretic administration of Ach compared with SNP was recorded with a laser Doppler technique, the data being analysed on a personal computer. RESULTS: Both Ach and SNP administration resulted in marked vasodilatation; the magnitude of the vasodilatation was similar in the three groups of women. CONCLUSION: Following iontophoretic administration of endothelial cell dependent or independent vasodilatators, laser Doppler measurement of blood flow demonstrated no microvascular endothelial cell dysfunction in pre-eclamptic women.

Temperature thresholds in the oropharynx of patients with obstructive sleep apnea syndrome.

The temperature thresholds for warmth and cold were determined on the oropharyngeal mucosa of 15 patients with obstructive sleep apnea syndrome (OSAS) and 15 age-matched nonsnoring control subjects. We found that six of the patients with OSAS were not able to detect either the upper (50 degrees C) or lower (25 degrees C) temperature limits of the test when recording from the tonsillar pillar, whereas all control subjects detected the temperature change within the measuring range. The OSAS patients showed a statistically significant higher threshold for warmth on the anterior tonsillar pillar, 46.8 degrees C (95% confidence interval 45.2-48.4) versus 42.5 degrees C (41.3-43.8) for the control subjects (p = 0.0006). The same was found on the tip of the tongue-40.1 degrees C (38.7-41.6) for OSAS patients and 38.2 degrees C (37.1-39.4) for the control subjects (p = 0.036). Determination of temperature thresholds on the skin is an established method of detecting a neuropathy. We speculate that patients with OSAS suffer from a neuropathy in the pharynx caused by prolonged and progressive trauma to the pharyngeal structures from vibration induced by snoring and/or stretching of the structures during apneas. A neuropathy may interfere with the normal stabilizing function of the pharyngeal muscles and with the local reflex mechanism preventing the upper airway from collapsing during inspiration. It is thus possible that snoring itself, by inducing a neuropathy in the pharynx, may contribute to the sequence of events that transform a snorer into a patient suffering from OSAS.

Non-invasive vs. invasive beat-to-beat monitoring of blood pressure.

The present study focuses on the accuracy in tracing fast beat-to-beat changes in blood pressure using a non-invasive technique. The measurements using a commercially available apparatus (Finapres, Ohmeda, USA) were compared to ipsilateral intra-arterial radial pressure. Eight patients were studied at rest, during deep breathing with a fixed rate of 6 breaths min-1, and during an exercise test on an ergometer cycle. A total of 900 systolic pressure values were included for statistical evaluation, covering a pressure range of 86-266 mmHg. On average the systolic correlation coefficient for the whole material was 0.97, with a range of 0.94-0.996. For mean pressure the correlation coefficient was on average 0.97, and for diastolic pressure 0.93. No systematic difference between the non-invasive and the invasive method was found, although for each individual patient a difference between direct and indirect measured blood pressure existed that could be relatively large (systolic pressure: average difference = 0.8 mmHg, SD = 16 mmHg). We found the method easy to handle and consider it excellently suited to track relative changes in blood pressure.

Confounding factors in non-invasive tests of neurovascular function in diabetes mellitus.

Disturbances of neurovascular function in the extremities may occur in patients with diabetes mellitus, exposure to toxic substances and chronic exposure to vibrating hand tools, as well as in Raynaud's phenomena. In these conditions symptoms of paraesthesia, finger numbness and blanching occur, so nerve conduction studies, vibration and temperature threshold measurements and neurovascular function tests are used for objective assessment of neurological dysfunction. The aim of the present study was to examine some factors which may confound quantitative neuro-vascular function measurements if used to assess neuropathy in diabetics. All subjects were consenting volunteers without exposure to known neurotoxic chemicals. The 5 groups were (a) healthy non-diabetic subjects not exposed to vibration (n = 10, mean age 52.3 yrs) (b) 2 insulin dependent and 8 non-insulin dependent diabetic subjects with a mean of 6 years treatment (n = 10, mean age 55.7 yrs) (c) maintenance employees exposed to high frequency pneumatic hand tools (n = 10, mean age 52.2 yrs) (d) subjects who were not diabetic or exposed to vibrating tools, but were being treated with the ACE-inhibitor enalapril 20 mg daily for hypertension (n = 5, mean age 54 yrs) (e) subjects who had smoked more than 10 cigarettes daily for at least 15 yrs (n = 10, mean age 51 yrs). Neurovascular tests included axon reflex responses measured by laser Doppler velocimeter evoked on the dorsum of the finger by iontophoresis of acetylcholine 16 mC in a circumferential chamber: cutaneous microvascular dilator responses to endothelial stimulation by iontophoretic application of the muscarinic agonist pilocarpine 16 mC and to direct nitrodilator sodium nitroprusside 16 mC. The skin temperature of the digits was held between 33 degrees and 34 degrees C during testing and dilator responses were measured as flux change by on-line computer analysis using 'Perisoft'. There was a significant reduction (P < 0.05) in the neurovascular responses of both diabetics and vibration--exposed subjects to acetylcholine and, in the case of vibration-exposed subjects, to pilocarpine, but nitroprusside responses were not significantly different. Our findings of reductions in neurovascular responses in diabetics and in subjects exposed to higher frequency vibration is consistent with recent epidemiological findings. Furthermore, subjects treated with an ACE-inhibitor (enalapril) showed significant reduction in acetylcholine-evoked axon reflex responses, while the test group of smokers showed a significant reduction in their dilator response to pilocarpine.(ABSTRACT TRUNCATED AT 400 WORDS)