Twenty-four-hour pattern of blood pressure and spectral analysis of heart rate variability in diabetic patients with various degrees of autonomic neuropathy. Comparison to standard cardiovascular tests.

We performed four cardiovascular tests of autonomic function (deep breathing, lying to standing, Valsalva manoeuvre, postural hypotension) and simultaneous 24h recordings of blood pressure (BP) and ECG in 35 normotensive diabetic subjects. Autoregressive power spectrum analysis of RR interval variability was applied to 24h ECG recordings to obtain for day and night periods power of low- (0.03-0.15 Hz, LF) and high-frequency (0.18- 0.40 Hz, HF) components, relative markers of sympathetic and vagal activity respectively, and their ratio (LF/HF), assumed as index of sympathovagal balance. Eighteen patients showed normal cardiovascular tests, 6 patients one abnormal heart rate test, 5 patients two abnormal heart rate tests, and 6 patients also abnormal postural hypotension test. In diabetic patients with increasing degree of autonomic neuropathy, there was a progressive reduction of day-night change in systolic BP (p < 0.01), of LF during the day (p < 0.01), of HF during the night (p < 0.04), of day-night change in HF (p < 0.02), and of day-night change in HF/LF (p < 0.03). Day-night change in systolic BP was related to postural hypotension (p < 0.001) and to deep breathing (p < 0.01). Day LF was related to lying to standing (p < 0.001), to postural hypotension (p < 0.005) and to deep breathing (p < 0.007). Night HF was related to deep breathing (p < 0.0002) and to lying to standing (p < 0.02). Day-night change in HF/LF was slightly related to deep breathing, lying to standing, and to postural hypotension (p < 0.04). In a multiple regression analysis including age, diabetes duration, and cardiovascular tests as independent variables, day-night change in BP and day LF were only related to postural hypotension, whereas night HF was related to deep breathing. In conclusion, in diabetic patients with increasing autonomic damage, there is a progressive impairment of nocturnal fall of BP and of sympathetic activity during the day, blunted nocturnal increase of vagal activity and lower circadian variation in sympathovagal balance. The significant but not very close correlation of day-night pattern of BP and sympathovagal activity to standard cardiovascular reflex tests, supports the independent usefulness of 24h BP monitoring and spectral analysis of heart rate variability in diabetic neuropathy.

Relationship between the circadian rhythms of blood pressure and sympathovagal balance in diabetic autonomic neuropathy.

In diabetic autonomic neuropathy, abnormal circadian patterns of blood pressure and sympathovagal balance with reduced fall of blood pressure and prevalence of sympathetic activity during the night have been described. To correlate the abnormalities of blood pressure to those of sympathovagal balance, we simultaneously performed 24-h noninvasive monitoring of blood pressure and ECG in 25 diabetic patients (45.6 +/- 13.6 yr of age with a 17.6 +/- 9.1 yr duration of diabetes) with various degrees of cardiovascular reflex impairment. Autoregressive power spectrum analysis of RR interval variability was applied to 24-h ECG recordings to obtain for day and night periods the mean power of low- (0.03-0.15 Hz) and high-frequency (0.18-0.40 Hz) components, which are relative markers of sympathetic and vagal activity, respectively, and their ratio (low frequency/high frequency), assumed as index of sympathovagal balance. Diabetic patients showed a lower percentage of day-night change in systolic blood pressure (9 +/- 5.48 vs. 11.6 +/- 4.78%, P < 0.037), a lower day low frequency (5.9 +/- 0.81 vs. 6.62 +/- 0.73 In-ms2, P < 0.001), a lower night high frequency (6.06 +/- 0.71 vs. 6.52 +/- 0.85 In-ms2, P < 0.05), a lower day low frequency:high frequency ratio (1.82 +/- 1.77 vs. 3.05 +/- 1.82, P < 0.01), and a lower percentage of day-night change in low-frequency:high frequency ratio (-13.4 +/- 109.9 vs. 28.7 +/- 29.7%, P < 0.05), when compared with control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired circadian modulation of sympathovagal activity in diabetes. A possible explanation for altered temporal onset of cardiovascular disease.

BACKGROUND: Diabetic subjects have a high incidence of cardiovascular accidents, with an altered circadian distribution. Abnormalities in the circadian rhythm of autonomic tone may be responsible for this altered temporal onset of cardiovascular disease. METHODS AND RESULTS: To assess circadian changes of sympathovagal balance in diabetes, we performed 24-hour power spectral analysis of RR interval fluctuations in 54 diabetic subjects (age, 44 +/- 2 years) with either normal autonomic function or mild to severe autonomic neuropathy and in 54 age-matched control subjects. The power in the low-frequency (LF, 0.03-0.15 Hz) and high-frequency (HF, 0.18-0.40 Hz) bands was considered an index of relative sympathetic and vagal activity, respectively. Diabetic subjects with autonomic abnormalities showed a reduction in LF compared with control subjects (5.95 +/- 0.12 In-msec2 versus 6.73 +/- 0.11, p < 0.001) and an even greater reduction in LF, particularly during the night and the first hours after awakening (5.11 +/- 0.18 In-msec2 versus 6.52 +/- 0.14, p < 0.001). Day-night rhythm in sympathovagal balance was reduced or absent in diabetic subjects compared with control subjects. CONCLUSIONS: Diabetic subjects with or without signs of autonomic neuropathy have a decreased vagal activity (and hence a relatively higher sympathetic activity) during night hours and at the same time of the day, during which a higher frequency of cardiovascular accidents has been reported. These observations may provide insight into the increased cardiac risk of diabetic patients, particularly if autonomic neuropathy is present.

[Transient cerebral ischemia and the risk factors]. / Ischemia cerebrale transitoria e fattori di rischio.

A retrospective study was carried out in a general medicine ward of 100 male patients suffering from their first transient ischemic attack (TIA) in order to evaluate the incidence of different cerebrovascular risk factors. The results were then compared with those from another group of 100 patients suffering from initial cerebral ischemic softening (CIS) in order to identify a cerebrovascular risk population taking into account clinical similarities and common and divergent features. The study revealed that age is the prime risk factor in the genesis of TIA, followed by arterial hypertension and hypercholesterolemia. From a comparison with the group of patients affected by initial CIS it was clear that TIA is typical of senility and is more closer correlated to age than other risk factors; therefore, che TIA population is an expression of those who have "survived" cerebrovascular death due to the lesser exposure to risk factors.

Clinical assessment of respiratory sinus arrhythmia by computerized analysis of RR interval and respiration.

Heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) are often considered as interchangeable terms. However, the application of power spectral analysis to describe spontaneous fluctuations in heart period has clearly shown that RSA is only a part of HRV, and that in specific situations their respective patterns may diverge. In order to quantify the RSA we have used a mathematical method based on combined spectral analysis of respiration and RR interval (cross-correlation function), and evaluated its performance in terms of reproducibility, sensitivity to parasympathetic withdrawal and in clinical evaluation of autonomic function. Compared to other indices of HRV the cross-correlation between RR interval and respiration showed a greater sensitivity to parasympathetic withdrawal, better reproducibility and a high sensitivity in detecting autonomic dysfunction in diabetic patients. These findings suggest that specific indices of RSA, such as the cross-correlation, can be a valid tool for the diagnostic approach to cardiac autonomic dysfunction.

Noninvasive assessment of the relationship between cardiac and autonomic function in diabetes.

In order to assess a possible relationship between left ventricular (LV) function and cardiac autonomic involvement in type-1 insulin dependent diabetes, we performed M-mode echocardiograms and autonomic function tests in 21 patients (mean age +/- SD, 38 +/- 11 years, range 18-55, 16 male and 5 female). In 7 patients and in 21 age-matched controls the echocardiogram was also recorded before and during handgrip. At rest, ventricular function abnormalities were found only in 4 subjects, and no significant correlation was found between echocardiographic parameters and autonomic function tests. Unlike controls, during handgrip diabetic subjects failed to increase peak Vcf and peak filling rate, and increased their left ventricular end-systolic diameter. The changes in LV parameters during handgrip were significantly correlated with resting autonomic function tests (p less than 0.025). Our results suggest that resting cardiac function may be normal in diabetics despite high incidence of abnormal autonomic tests. Latent abnormalities of left ventricular function can be unmasked by acute haemodynamic challenges such as handgrip, and are correlated with abnormalities in autonomic function tests.

[The variability of the heart rate, arterial pressure and peripheral circulation as the indices of autonomic control in essential hypertension]. / Variabilità della frequenza cardiaca, della pressione arteriosa e del circolo periferico quale indice del controllo autonomico nell'ipertensione essenziale.

In recent years the influence of autonomic nervous system on cardiac rhythm and blood pressure has been increasingly studied by analysis of cardiovascular fluctuations, particularly in diabetic and normal persons under various physiologic conditions, while still few data exist on essential hypertension. To characterize the autonomic cardiovascular control in essential hypertension we studied 22 untreated hypertensives, diagnosed within 1 year (mean age 43 +/- 2 years, mean +/- SEM) and 16 age-matched normotensives. Recordings of RR interval, breathing activity, noninvasive blood pressure (Finapres) and skin arteriolar flow (infrared photoplethysmogram) were obtained while in supine position and after sympathetic activation induced by passive transition to upright posture (tilting table). Autoregressive power spectral analysis was then carried out, and low- (0.03-0.15 Hz, LF) and high-frequency fluctuations (0.15-0.35 Hz, HF) were measured. LF and HF have been considered as markers of sympathetic and parasympathetic activity on the heart, respectively, and as markers of sympathetic and mechanic chest activity on the circulation, respectively. In supine position both cardiac and vascular variability were similar in both hypertensive and normotensive groups. After tilting however the increase in the sympathetic component of cardiac variability was blunted in hypertensives with respect to normotensives (hypertensives LFnu from 43.6 +/- 4.7 nu to 59.4 +/- 5.1 nu, p less than 0.005; normotensives LFnu from 36.9 +/- 3.3 nu to 83.4 +/- 2.6 nu, p less than 0.001), the increase in LFnu being statistically (p less than 0.001) reduced in the hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic nervous system and microcirculation in diabetes.

In order to evaluate the occurrence of sympathetic impairment of skin microvascular control in diabetes, we evaluated the spectral analysis of forearm skin laser-Doppler fluctuations in nine insulin-dependent diabetic subjects and in 21 controls of similar age. Low-frequency oscillations (around 0.1 Hz) were significantly lower in diabetics than in controls (2.333 +/- 0.340 (mean +/- SEM) units vs. 3.486 +/- 0.093 units, P less than 0.001), whereas no significant differences were found between the two groups regarding high-frequency respiration-related oscillations. These results suggest that the loss of rhythmicity in diabetic subjects is selectively related to low-frequency oscillations, mostly under sympathetic control, and is likely to be dependent on autonomic abnormality.

Relationship between retinal ischemia and cardiovascular autonomic damage in diabetes.

In order to investigate the relationship between ischemic diabetic retinopathy and cardiac autonomic dysfunction we studied 40 diabetic patients (mean age +/- SEM: 48 +/- 2 years). Retinopathy was evaluated by fluorescein angiography and patients were divided into three groups: a) with ischemic retinopathy (15 patients), b) with edematous retinopathy (13 patients) and c) without retinopathy (12 patients). Cardiac autonomic function was assessed by 4 tests based on cardiovascular reflexes (heart rate response to Valsalva maneuver and to deep breathing; systolic blood pressure fall after standing and diastolic blood pressure rise during handgrip) and by the cross-correlation test, a computerized technique for the analysis of respiratory sinus arrhythmia based on spectral analysis of electrocardiographic and respiratory signals. Abnormalities of cardiac autonomic tests were present in 26/40 patients (65%); considering the retinal angiographic classification, autonomic test abnormalities were found in 13/15 (86.6%) patients with ischemic retinopathy, in 7/13 (53.9%) patients with edematous retinopathy and in 6/12 (50%) patients without retinopathy. The prevalence of cardiac autonomic dysfunction was significantly higher (p less than 0.005) in the ischemic retinopathy group compared to the other groups. These results show a strong association between ischemic retinopathy and cardiac autonomic dysfunction.

Cardiac autonomic dysfunction in obese subjects.

1. The prevalence of cardiac autonomic alterations was evaluated in 23 obese subjects with body mass index 37.2 +/- 3.03 kg/m2 (mean +/- SD), compared with 78 controls with body mass index 22.5 +/- 2.6 kg/m2 (P less than 0.001). 2. Cardiac autonomic function was assessed by four standard tests (heart rate response to deep breathing and to the Valsalva manoeuvre, systolic blood pressure fall after standing and diastolic pressure rise during handgrip) and by the cross-correlation test, a new method of computerized analysis of respiratory sinus arrhythmia based on spectral analysis of electrocardiographic and respiratory signal. 3. Considering tests indicative of parasympathetic function, only the heart rate response to the deep breathing and the cross-correlation test were significantly lower in the obese than in the control group [deep breathing = 13.95 +/- 8.65 beats/min (mean +/- SD) vs 24.5 +/- 7.65, P less than 0.001; cross-correlation 4.28 +/- 0.74 units vs 5.14 +/- 0.63, P less than 0.001]. Deep breathing and/or cross-correlation were abnormal in 10 (43.5%) obese subjects (deep breathing: seven subjects, cross-correlation: eight subjects). No significant difference between groups was found for the response to the Valsalva manoeuvre: the Valsalva ratio was 1.69 +/- 0.45 in obese subjects and 1.88 +/- 0.33 in controls (P = NS). The Valsalva ratio was abnormal in three obese subjects. 4. No significant differences were found between groups for tests indicative of sympathetic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross correlation of heart rate and respiration versus deep breathing. Assessment of new test of cardiac autonomic function in diabetes.

Cross correlation is a mathematical function whereby spectral analysis is used to describe the relationship between heart-rate fluctuations (256 R-R intervals) and respiration (simultaneously obtained by pneumotacograph). To assess its usefulness for testing autonomic integrity, cross correlation and deep breathing were compared in 141 diabetic subjects (aged 39 +/- 14 yr) and in 77 control subjects (aged 33 +/- 13 yr). To characterize patients, Valsalva maneuver, 30:15 ratio, tilt, and handgrip tests were performed in 96 of these patients; 23 had two or more abnormal tests (group A), 28 had one (group B), and 45 had none (group C). Sensitivity to parasympathetic withdrawal was compared in 9 control subjects (aged 26 +/- 4 yr) by four sequential 0.01-mg/kg i.v. atropine administrations. Reproducibility was compared in 11 control subjects (aged 25 +/- 2 yr) by repeating the tests four times for 2 consecutive days. Considering all 141 patients, cross correlation and deep breathing were less than 2SD of the mean of control subjects in 64 and 36 subjects, respectively. Considering patients who also performed other tests of autonomic function, cross correlation and deep breathing were less than 2SD of the mean of controls in 42 and 30 subjects, respectively (group A, 20 and 15; group B, 12 and 9; group C, 10 and 6). Cross correlation had better reproducibility than deep breathing (C.V. 10.3 vs. 30.6% at 6 breaths/min) and greater sensitivity to atropine (after the 1st injection, cross correlation and deep breathing decreased to 34.6 and 48.2% of baseline values, respectively; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Cerebral ischemic malacia. A retrospective study of CAT scan-documented cases]. / Il rammollimento ischemico cerebrale. Studio retrospettivo su casistica TAC documentata.

One hundred male patients affected by ischaemic stroke were studied with the use of CT scans. A clinical-biohumoral pattern was traced for every patient, with particular regard to the incidence of risk factors for stroke of which systolic arterial hypertension, appear to be the most frequent. It would be useful to extend this research to female patients as well in order to discover any significant differences between sexes.

Relationship between fluctuations in heart rate and asymptomatic nocturnal ischaemia.

In order to quantify autonomic changes related to asymptomatic nocturnal myocardial ischaemia, we analyzed heart rate fluctuations recorded during Holter monitoring in 9 subjects with coronary heart disease (21 episodes) and in 11 age-matched controls. R-R interval spectral analysis was computed in sequences of 256 heart beats, taken during the ischaemic episode, 4, 8 and 60 minutes before, and 4 and 60 minutes after. Mean heart rate, R-R interval variability (assessed by R-R interval standard deviation), low and high (respiration-linked) frequency components of R-R interval spectrum were evaluated. Mean heart rate and R-R interval variability increased only during ischaemia (from 62.9 to 73.3 beats/minute, P less than 0.02, and from 39 to 88 msec, P less than 0.01, respectively). While high-frequency components of heart rate variability remained unchanged, low-frequency peak increased during ischaemia (from 9.4 to 43.3 sec2 X 10(-3)/Hz, P less than 0.01) and also 8 minutes (P less than 0.05) and 4 minutes before (P less than 0.05). Despite a moderate increase of heart rate occurring only during ischaemia, the early rearrangement of heart rate fluctuations suggests the occurrence of changes of autonomic tone before the electrocardiographic onset of ischaemia. Due to its limited amount, this phenomenon appears to be a consequence, most likely unspecific, of factors responsible for the genesis of myocardial ischaemia.

[Clinical definition of asymptomatic abdominal masses]. / Definizione clinica di masse addominali asintomatiche.

Five patients with asymptomatic abdominal masses (abdominal leiomyosarcoma, giant hydronephrosis, renal cell carcinoma, squamous cell carcinoma of the lung metastatic to the adrenal gland, retroperitoneal non-Hodgkin's lymphoma) are reported. Non invasive investigations such as Echography and Computed Tomography, are very advantageous for the quick diagnosis of asymptomatic abdominal masses and for subsequent therapy.

Bedside diagnosis of cardiac autonomic damage by computerized analysis of heart rate-respiration relationship.

In this study we propose a method for the analysis of the relationship between heart rate changes and respiration as a possible diagnostic tool for cardiac autonomic damage. The method consists in recording R-R intervals and respiratory amplitude by a suitably equipped personal computer, and by evaluating the cross-correlation peak between the two signals. This mathematical function appeared to be more sensitive to the degree of concordance between the two signals, rather than their absolute amplitude. The cross-correlation appeared to be lower in diabetics with autonomic dysfunction, markedly decreased after injection of atropine (only in normals), slightly increased after propranolol. Hyperpnea increased the cross-correlation peak between 3-18 breaths/min in normals, but only at lower frequencies, if at all, in diabetic subjects with various degrees of autonomic dysfunction. The cross-correlation showed the best reproducibility among R-R change tests. These preliminary results suggest that this method may provide new information on autonomic integrity and a substantial advantage in terms of reproducibility.