Carmela Bucca

Abnormal passive head-up tilt test in subjects with symptoms of anxiety power spectral analysis study of heart rate and blood pressure

Previous reports that subjects with anxiety symptoms are at higher risk of sudden death may imply that anxiety induces stable sympathetic hyperactivity. To address this subject, in persons with and without anxiety symptoms, we evaluated autonomic nervous system activity by power spectral analysis of heart-rate and arterial-pressure variability at baseline (rest) and after sympathetic stress (tilt). The 117 subjects selected (56 men and 61 women, age range 23-87 years) were subdivided by questionnaire into three groups: 49 subjects (mean age 55.8+/-2.8 years) had no anxiety symptoms; 36 (mean age 56.8+/-3.6 years) had one anxiety symptom; and 32 (mean age 55.0+/-2.9 years) had two or more anxiety symptoms. Power spectral analysis recognizes three main components: high frequency (HF), chiefly reflecting vagal efferent activity; low frequency (LF), reflecting sympathetic activity; and very-low-frequency (VLF). The ratio of low- to high-frequency powers (LF:HF) of heart rate variability provides a measure of sympathovagal balance. Power spectral analysis showed that subjects with two or more anxiety symptoms had significantly lower resting values for all power spectral components of heart rate variability: total power (TP), VLF, LF, and HF than did symptomless controls (P<0.05). The highest anxiety-score groups also had a higher baseline LF:HF than the other two groups (P<0.05). Their resting LF:HF ratio correlated positively with anxiety symptom scores (r=0.72, P<0.0001). Tilt induced opposite results: the highest anxiety-score groups had a significantly lower LF:HF ratio; the ratio correlated inversely with their anxiety scores (r=-0.69; P<0.0001). Recordings of resting systolic arterial pressure variability showed that the group with two or more anxiety symptoms had significantly higher LF power (P<0.05) than symptomless controls. Our findings suggest that persons with high anxiety scores have baseline cardiac sympathetic hyperactivity. They also have low heart-rate variability, possibly explaining their susceptibility to sudden cardiac death.

Heart Rate and Blood Pressure Variabilities in Salt-Sensitive Hypertension

In salt-sensitive hypertension, a high sodium intake causes plasma catecholamines to rise and pulmonary baroreceptor plasticity to fall. In salt-sensitive and salt-resistant hypertensive subjects during low and high sodium intakes, we studied autonomic nervous system activity by power spectral analysis of heart rate and arterial pressure variabilities and baroreceptor sensitivity. In all subjects, high sodium intake significantly enhanced the low-frequency power of heart rate and arterial pressures at rest and after sympathetic stress. It also increased heart rate and arterial pressure variabilities. During high sodium intake, salt-sensitive hypertensive subjects had significantly higher low-frequency powers of systolic arterial pressure (7.5 mm Hg2, P < .05) and of heart rate at rest (59.2 +/- 2.4 normalized units [NU], P < .001) than salt-resistant subjects (6.6 +/- 0.3 mm Hg2, 55.0 +/- 3.2 NU) and normotensive control subjects (5.1 +/- 0.5 mm Hg2, 41.6 +/- 2.9 NU). In salt-sensitive subjects, low sodium intake significantly reduced low-frequency normalized units (P < .001) and the ratio of low- to high-power frequency (P < .001). High-sodium intake significantly increased baroreflex sensitivity in control subjects (from 10.0 +/- 0.7 to 17.5 +/- 0.7 ms/mm Hg, P < .001) and salt-resistant subjects (from 6.9 +/- 0.7 to 13.9 +/- 0.9, P < .05) but not in salt-sensitive subjects (7.4 +/- 0.3 to 7.9 +/- 0.4). In conclusion, a high sodium intake markedly enhances cardiac sympathetic activity in salt-sensitive and salt-resistant hypertension. In contrast, although reduced sodium intake lowers arterial pressure and sympathetic activity, it does so only in salt-sensitive subjects. Hence, in salt-resistant subjects, neither arterial pressure nor sympathetic activity depends on salt intake. During a high sodium intake in normotensive subjects and salt-resistant hypertensive subjects, increased sympathetic activity is probably compensated by enhanced baroreflex sensitivity.

Autonomic Modulation and QT Interval Dispersion in Hypertensive Subjects With Anxiety

Anxiety is associated with an increased risk of sudden death. QT dispersion is a marker of cardiac repolarization instability and is seen in conditions of high risk of sudden death. The purpose of this study was to evaluate autonomic nervous system control and QT dispersion in hypertensive subjects with anxiety symptoms. In a recent preliminary study, we observed that hypertensive individuals reporting high scores on a self-assessment anxiety scale had more marked left ventricular hypertrophy. In 105 hypertensive subjects divided into 3 groups according to severity of anxiety, we evaluated autonomic control by short-term power spectral analysis of RR and arterial pressure variability at rest (baseline) and during sympathetic stress (tilt test), left ventricular mass index, and heart rate-corrected QT (QTc) dispersion. At baseline, hypertensive subjects with higher anxiety symptom scores had significantly lower high-frequency RR values expressed in absolute terms (P<0.05) and in normalized units (P<0.05) than their counterparts without anxiety symptoms. Hypertensive subjects with anxiety also had a higher mean left ventricular mass index (P<0.001) and greater QTc dispersion (P<0.001). Both indexes and high frequency (P<0.05) correlated with severity of anxiety. These findings suggest that anxiety is associated with autonomic imbalance. This condition could favor an increase in left ventricular mass. Myocardial hypertrophy alone or combined with neuroautonomic imbalance may lead to QT dispersion.

Power spectral analysis of heart rate in subjects over a hundred years old

Altered autonomic regulation of cardiac function may contribute to the onset of cardiovascular disease and provide a substrate for malignant ventricular arrhythmias. This study was designed to assess cardiovascular neuroautonomic status in healthy subjects with short-term power spectral analysis of heart rate variability, including a group over 100 years of age, to identify a neuroautonomic pattern that could help to protect ultra-centenarians against cardiovascular disease. One hundred and twelve subjects (22 men and 90 women, age range 20 to 107 years) were subdivided into five age groups: <40 years (N=26, mean age 30.6+/-0.9); 41 to 60 years (N=27, mean age 51.9+/-1.2); 61 to 80 years (N=37, mean age 70.3+/-1.1); 81 to 100 (N=10, mean age 85.2+/-0.8) and older than 101 years (N=13, mean age: 103.6+/-0.6). Power spectral analysis with autoregressive algorithm provides two indexes of autonomic activity: a low-frequency component oscillating around 0.10 Hz, mainly reflecting sympathetic activity and a high-frequency component around 0.30 Hz, reflecting parasympathetic activity. Subjects 40 years of age or younger had significantly higher spectral high-frequency power values expressed in logarithmic form than the other age groups (P<0.05), the age group from 41 to 100 years had values similar to those of the other groups. However, the age group over 101 years had significantly higher values than the group from 81 to 100 years (P<0.05). Low-frequency spectral density expressed in logarithmic form and in normalized units decreased with age (P<0.0001). These data confirm an age-related decline in sympathetic activity. Compared with elderly subjects from 81 to 100 years of age ultra-centenarians have significantly higher spectral parasympathetic indexes. Parasympathetic predominance may be the neuroautonomic feature that helps to protect ultra-centenarians against cardiovascular disease.

Age-dependent influence on heart rate variability in salt-sensitive hypertensive subjects

OBJECTIVE: The known association between systemic arterial hypertension in its initial stages and increased sympathetic nervous system drive prompted us to evaluate the influence of age on autonomic nervous system function in subjects with salt‐sensitive arterial hypertension.

QT interval dispersion and autonomic modulation in subjects with anxiety

This study was designed to assess Q-T interval dispersion as a marker of electrical instability in subjects with anxiety. Recent observations have shown that the presence of anxiety symptoms increases the risk of sudden death. The Kawachi anxiety questionnaire identified 29 subjects (male/female ratio 13:16) who scored 0, 22 subjects (male/female ratio 14:8) who scored 1, and 37 subjects (male/female ratio 13:24) who scored 2 or more. In all subjects we measured electrocardiographic interlead QT dispersion and autonomic function through spectral analysis of R-R interval and blood pressure variabilities and left ventricular mass. Compared with subjects who scored 0, those reporting 2 or more symptoms showed increased heart rate-corrected QT dispersion (54.9+/-1.7 ms vs. 34.9+/-3.2 ms, P<.001), sympathetic modulation (normal logarithm low-frequency power/high-frequency power 0.59+/-0.1 vs. 0.12+/-0.04, P<.05), and left ventricular mass (120.7+/-3.5 g/m2 vs. 97.9+/-2.8 g/m2, P<.001). Probably because it augments sympathetic activity, anxiety causes left ventricular mass to increase and, like hypertension, increases heart rate-corrected Q-T interval dispersion. The consequent electrical instability could be the substrate responsible for inducing fatal ventricular arrhythmias.

Left ventricular mass and heart rate variability in middle-aged and elderly salt-sensitive hypertensive subjects

Previous reports have shown that in salt-sensitive hypertension a high dietary salt intake can increase sympathetic activity. We evaluated the influence of the autonomic nervous system on myocardial hypertrophy by power spectral analysis of heart rate variability in middle-aged and elderly salt-sensitive hypertensive subjects. We compared autonomic nervous system activity in 32 salt-sensitive hypertensive patients (15 subjects with mean age, 42.4+/-2.4 years and 17 subjects with mean age, 74.6+/-1.6 years) and 20 age-matched normotensive controls. Power spectral analysis detects four spectral components: total power (TP), high-frequency (HF), low-frequency (LF) and very-low-frequency (VLF) power. In the elderly subjects we found an association between the left ventricular mass index (LVMI) and the following variables: very-low frequency (P<0.0001), 24-h urinary sodium excretion (P<0.0001) and diastolic blood pressure (DBP) (P<0.0001). In contrast, in middle-aged subjects we found a significant association between the LVMI and LF (P<0.001). In middle-aged, but not in elderly salt-sensitive hypertensive subjects, increased sympathetic activity correlated with the LVMI (P<0.0001). Our findings suggest an association between sympathetic hyperactivity and the LVMI in middle-aged subjects with salt-sensitive hypertension.

Sympathetic activity and anxiety in hypertensive and normotensive subjects

Summary Epidemiological studies have shown that chronic anxiety is associated with a higher risk for sudden death through sympathetic hyperactivity. We studied the autonomic nervous system activity by spectral analysis of heart rate and blood pressure variability at rest in 33 normotensive and in 31 hypertensive subjects with anxiety symptoms. Power spectral analysis recognizes two main components: low frequency (LF), reflecting mainly sympathetic activity, and high frequency (HF), reflecting mainly vagal efferent activity. The ratio of low to high frequency powers (LF/HF) of heart rate variability provides a measure of sympathovagal balance. Power spectral analysis showed that the anxiety correlated positively with resting LF/HF ratio but correlated inversely with aging. In conclusion, we demonstrated an evidence for the prevalence of sympathetic indexes in subjects with anxiety symptoms. These are valuable markers of higher risk for sudden death and so, our opinion is that there is a natural selection with aging.

The Role of the Autonomic Nervous System in Congestive Heart Failure

Altered sympathovagal balance could be a substrate for malignant ventricular arrhythmias in congestive heart failure. The aim of this study is to assess neuroautonomic function by power spectral analysis in patients with congestive heart failure and the effects of treatment with Carvedilol in these patients. We compared the LF/HF ratio of all patients at baseline and after sympathetic stress (tilt). In group I, we considered 10 patients with congestive heart failure and 10 controls mean aged 60 years, while in group II were 10 patients with heart failure 70 years old and normal subjects age-matched. In group I, at rest the subjects with congestive heart failure had a significantly greater LF/HF (p<0.001) than controls. In contrast, it increased significantly after tilt in control subjects. In group II, at rest LF/HF did not differ between patients with congestive heart failure and normal subjects, while after tilt it resulted higher in controls (p<0.05). After a month of 25 mg daily of Carvedilol administration in patients with heart failure in group I, both at rest and after tilt, LF/HF was significantly greater in patients in wash-out than treated (p<0.001). In group II there weren’t significant differences both at rest and after tilt. This study showed increase of sympathetic activity in patients with congestive heart failure mean aged 60 years, less evident in patients aged 70 years. Carvedilol can exert beneficial myocardial effects in these patients, because reduces morbidity and mortality and can favorably influence the course of disease and prolong survival.

Baroreflex sensitivity in the elderly with silent myocardial ischemia

In order to assess high-pressure baroceptor sensitivity and parasympathetic function in elderly patients with silent myocardial ischemia, we selected 45 inpatients in our geriatric unit for a prospective cohort study of patients with coronary heart disease. All patients were over 65 years of age (37 men and 8 women) and had coronary heart disease, documented by an angiographic study and electrocardiographic evidence of myocardial ischemia during exercise stress testing, performed according to the Bruce protocol. The subjects were divided in three subgroups: group 1 (22 patients) with electrocardiographic and echocardiographic history of myocardial infarction but no angina chest pain during exercise testing; group 2 (13 patients) with no exercise induced chest pain; and group 3 (10 patients) with exercise-induced chest pain. Baroceptor sensitivity was assessed in all subjects, by evaluating heart rate changes expressed in RR interval on the basis of changes in the mean arterial pressure during intravenous infusion of stepwise doses (50-100 and 150 microg) of phenylephrine hydrochloride. Heart rate changes were also evaluated during overshoot of the Valsalva maneuver (Valsalva max.), providing an index of parasympathetic activity. Our results showed that group two patients (only silent ischemia) had significantly (P>0.001) greater baroceptor sensitivity than the other two groups (group 2; 15.2+/-1.9 ms/mmHg; group 1: 10.0+/-1.7 ms/mmHg; and group 3: 9.8+/-1.7 ms/mmHg). Group two also showed a significant positive correlation (r=0.58; P<0.05) between baroceptor sensitivity and end-diastolic pressure and a significant inverse correlation (r=-0.672; P<0.05) between baroceptor sensitivity and the ejection fraction. Group 2 patients had a significantly longer RR interval than group 1 (P<0.05) and group 3 (P<0.05); a significant positive correlation (r=0.620; P<0.05) between Valsalva max. and end-diastolic pressure; and a significant inverse correlation (r=0.694; P<0.05) between Valsalva max. and the ejection fraction. Valsalva max. and baroceptor sensitivity correlated significantly in all three groups (group 1, r=0.707; P<0.001; group 2, r=0.94; P<0.001; and group 3; r=0.833; P<0.05). In conclusion our data suggest that elderly patients with silent ischemia appear to have an increased capacity for evoking parasympathetic reflexes that could inhibit pain perception.