M. Cacciafesta

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.

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.

Influence of sex and age on blood pressure variability

The aim of this study has been to identify changes of 24-h blood pressure variability, as related to age and sex in hypertensive subjects. As regards this point several international studies have shown the increase of morbidity and mortality caused by cardiovascular diseases in postmenopausal women produced by a lack of sex hormones, which had protected the women until this period. Each hypertensive subject was submitted to an ambulatory blood pressure monitoring (ABPM) and two variability indexes were obtained: S.D. and coefficient of variation (CV). The results have shown a strict correlation between blood pressure variability and age, without significant sex-related differences. A decrease of blood pressure variability and mean blood pressure (BP) values have also been found, in the night-time with respect to the day-time data; it was more pronounced in females than in males but this would not seem an age-related difference. Despite the fact that the correlation between blood pressure variability and age is very significant in every considered period in males, it has been found that women have statistical differences only in the day-time and in the nocturnal diastolic blood pressure (DBP) fluctuations. This might be caused by other independent factors, such as a postmenopausal lack of sex hormones.

Platelet size and left ventricular hypertrophy in hypertensive patients over 50 years of age

Abstract. Both mean platelet volume (MPV) and left ventricular hypertrophy have been described as associated with increased risk for vascular events. Seventy‐six hypertensive patients (37 M and 39 F) over 50 years of age were studied. They were divided into subgroups according to the presence of left ventricular hypertrophy (LVH = LV mass index >125 gm‐2, when LV mass was assessed by M‐mode echocardiography according to Penns Convention). MPV was 3% higher in hypertensive patients with LVH compared with those without LVH (P>0.05) and it was associated with the occurrence of LVH (chi‐square = 8.44, P= 0.042). MPV significantly correlated with left ventricular mass index (r= 0.298, P= 0.004) and interventricular septum thickness (r= 0.231, P= 0.022). Both correlations remained significant after adjustment for age, blood pressure and glycaemia. MPV seemed to be associated with increased left ventricular mass and interventricular septum thickness in middle‐aged to elderly hypertensive patients.

Carvedilol in elderly patients with chronic heart failure, a 12 weeks randomized, placebo controlled open trial

The encouraging results of recent multicenter clinical trials conducted in the US on the effect of carvedilol therapy in patients with chronic heart failure, prompted us to verify its tolerability in a group of elderly patients. For the open, randomized, placebo-controlled study, we selected 40 patients (28 men and 12 women, mean age 76.8+/-5.9 years) with mild, moderate or severe chronic heart failure. Exclusion criteria included dementia, chronic hepatitis, renal failure, severe vascular disease and respiratory failure. All patients were receiving treatment with digitalis, furosemide and ACE inhibitors. The study lasted 12 weeks. During the first week, all subjects received oral placebo or carvedilol, at a dose of 6.25 mg twice daily. The twice daily dose was then increased to 12.5 mg during weeks 2-4 and to 25 mg from weeks 5-12. At 0, after the 2 weeks of run-in, 4 and 12 weeks patients underwent assessment of systolic and diastolic blood pressure, heart rate, left ventricular ejection fraction, cognitive status and functional ability. Our findings indicate that elderly patients with congestive heart failure tolerate carvedilol therapy well. Carvedilol slightly improves heart function without altering functional or cognitive ability. A larger-scale trial in geriatric patients is now required to determine whether this treatment will reduce serious morbidity or mortality from heart failure.

Correlation between MMSE performance, age and education in centenarians

Summary According to numerous investigations, age and education are in correlation with mini-mental state examination (MMSE) scores. However, several of the studies are based on cohorts not including elderly over 90 years of age. We assessed both the independent and joint effects of these factors on MMSE performance in a group of 101 Italian centenarians with the aim of better understanding how age and years of schooling are associated with changes of cognitive status in the longest living patients. Our data demonstrate that the distribution of the MMSE has a wide range in centenarians: mean score was 18.7 ± 7.4 and 43 % of them were included within the normal or borderline area. There were not significant differences by sex. As expected, there is an increase in the prevalence of cognitive impairment as educational level decreases. A cutoff point of 6 years of schooling has emerged as discriminant for a two level distribution of MMSE scores. While the general population scores progressively increase with the passage from one lower category of schooling to the next, centenarians show a single level of increase which entirely accounts for the differences between subjects. Furthermore, centenarians with lower educational level are at higher risk for cognitive deterioration prior to death.

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.