Gianfranco Piccirillo

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.

Age-adjusted normal confidence intervals for heart rate variability in healthy subjects during head-up tilt

PURPOSEnAging leads to a decline in autonomic nervous system function. In this study, designed to assess the influence of age on neuroautonomic regulation of cardiac activity, heart rate variability was measured by power spectral analysis and normal ranges were determined in a population of healthy subjects.nnnPATIENTS AND METHODSnIn 83 healthy volunteers (42 men and 41 women; age range 25-85 years) autonomic nervous system function was assessed by autoregressive spectral analysis of heart rate variability in clinostatism and after passive orthostatic load (head-up tilt). The analysis considered two spectral components relevant to the study of the autonomic nervous system--high-frequency power (approximately 0.05 Hz) and low-frequency power (approximately 0.10 Hz)--and the ratio between them. Low-frequency spectral components, in particular the ratio between low- and high-frequency spectra, reflect sympathetic activity; high-frequency components reflect parasympathetic activity.nnnRESULTSnFor data comparison, the study group was subdivided into three age groups: 25 subjects (12 men and 13 women) under 44 years of age; 28 (15 men and 13 women) aged 44-64 years; and 30 (15 men and 15 women) over 64 years of age. The natural logarithms and normalized units of low- and high-frequency power, and the low-to-high power ratio were used to calculate 95% confidence intervals. Power spectral analysis at baseline and after postural tilt showed significantly higher low-frequency power of heart rate variability (P < 0.05), natural logarithm of power (P < 0.001) and normalized units (P < 0.001) in the two younger groups than in the oldest group. The two younger age-groups also had significantly increased high-frequency power (P < 0.05) and natural logarithm of power (P < 0.05). The oldest age group had significantly increased high-frequency power analyzed in normalized units (P < 0.001).nnnCONCLUSIONnThe age-related lowering observed in nearly all the spectral frequency components of heart rate variability confirms in healthy subjects that autonomic nervous system function declines with age.

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.

Influence of Vitamin C on Baroreflex Sensitivity in Chronic Heart Failure

Abstract— Chronic heart failure (CHF) reduces baroreflex sensitivity. Low baroreflex sensitivity, a risk factor for sudden death, could arise partly from CHF‐dependent endothelial dysfunction. Vitamin C at high doses has a protective role against CHF‐related endothelial damage. This study was conducted to investigate the effect of vitamin C on baroreflex sensitivity in CHF. A study group of 33 subjects with CHF secondary to postischemic dilated cardiomyopathy with an ejection fraction <=35% and a control group (11 subjects) underwent assessment of baroreflex sensitivity by the phenylephrine method and an autonomic nervous system study by power spectral analysis. Variables were assessed after infusion of placebo and high doses of vitamin C (2.5 mg). In subjects with CHF, baroreflex sensitivity was significantly higher after vitamin C than after placebo infusion (placebo: 4.1±0.4 versus vitamin C: 5.3±0.5 ms/mm Hg, P <0.001). Low‐frequency of R‐R (LFRR), expressed in normalized units (NU) (P <0.05); LF/high‐frequency (HF) ratio (P <0.05), and LF of SBP (LFSBP) decreased significantly; HF power (P <0.05), and [alpha]‐HF (P <0.001) increased. Conversely, in the control group, baroreflex sensitivity and other spectral variables measured at baseline, after placebo, and after vitamin C infusion remained statistically unchanged (placebo: 10.2±0.1 versus vitamin C: 10.0±0.2 ms/mm Hg, NS). Acute administration of vitamin C at high doses improves baroreflex sensitivity and vagal sinus modulation in patients with CHF. This finding could have notable clinical and therapeutic implications. Key issues to understand are whether the beneficial effect persists during chronic administration and whether it helps to improve survival.

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.

Heart rate variability in hypertensive subjects

Hypertension is often associated with findings of sympathetic hyperactivity. Evidence shows that adrenergic receptor stimulation can induce left ventricular hypertrophy. Using an autoregressive algorithm in a power spectrum analysis of heart-rate variability in 14 subjects with mild hypertension (mean age 41 +/- 9.0 years) and 9 age-matched normotensives we compared autonomic nervous system function at baseline (rest) and during sympathetic stress (passive head-up tilt). The spectrum comprised four spectral frequency-domains: total power (0.0033-0.40 Hz), high-frequency power (0.16-0.40 Hz), low-frequency power (0.04-0.15 Hz) and very-low-frequency power (0.0033-0.04). The high-frequency spectral component predominantly reflects vagal activity, the low-frequency component sympathetic nervous system activity. The ratio between low-and high-frequency power expresses the sympathovagal balance. Results were expressed as natural logarithms of power and normalized units. In addition, we compared spectral densities obtained, with the left ventricular mass index evaluated by M-mode echocardiography. Hypertensive subjects had greater low-frequency and low-high frequency ratio values (P < 0.001) than normotensive controls. They also had a low capacity for increase after tilt. Multiple regression analysis showed that the left-ventricular mass index was independently associated with the body mass index (P < 0.0027), very-low frequency (P < 0.043), and low frequency (P < 0.0138) expressed as the natural logarithm, low-high frequency ratio (P < 0.0172) and systolic blood pressure (P < 0.0353). Our findings confirm enhanced sympathetic activity in hypertensive subjects. They also indicate a close association between the left-ventricular mass index and spectral indices of sympathetic activation.

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.

Heart rate and blood pressure variability in subjects with vasovagal syncope

Autonomic nervous system control in subjects with vasovagal syncope is controversial. In the present study, we used short-term spectral analysis to evaluate autonomic control in subjects with recurrent vasovagal syncope. We assessed the ability of spectral indices of HR (heart rate) variability to predict tilt-test responses. A series of 47 outpatients with recurrent vasovagal syncope and with positive responses to head-up tilt testing underwent a further study of RR variability during controlled breathing at rest and during tilt testing. During controlled breathing, RR interval variability of total power (TP(RR); P<0.001), low-frequency power (LF(RR); P<0.05), high-frequency power (HF(RR); P<0.001) and HF expressed in normalized units (HFnu(RR); P<0.001) were all higher, and LF expressed in normalized units (LFnu(RR)) and LF/HF ratio were lower in subjects with vasovagal syncope than in controls (P<0.001). To assess the ability of spectral components of RR variability to predict tilt-test responses, we prospectively studied 109 subjects with recurrent vasovagal syncope. The two normalized measures, HFnu(RR) and LFnu(RR), determined during controlled breathing alone predicted a positive tilt-test response (sensitivity, 76%; specificity, 99%; positive predictive value, 96%; and negative predictive value, 90%). During tilting, subjects with vasovagal syncope had lower SBP (systolic blood pressure; P<0.05), LF component of peak SBP variability (LF(SBP)) and LFnu(RR) than controls, and higher TP(RR), HF(RR), HFnu(RR) and alpha HF (P<0.001). These spectral data indicate that vagal sinus modulation is increased at rest in subjects with vasovagal syncope. Spectral analysis of RR variability during controlled breathing, a procedure that predicts tilt-test responses, could be a useful guide in choosing the method of tilt testing.

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.