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PROF G.PICCIRILLO
Principali pubblicazioni degli ultimi anni
Effects of sildenafil citrate (viagra) on cardiac repolarization and on autonomic control in subjects with chronic heart failure. PICCIRILLO G, NOCCO M, LIONETTI M, MOISE A, NASO C, MARIGLIANO V, CACCIAFESTA M BACKGROUND: Cases of sudden death associated with sildenafil citrate use have been reported in men with coronary artery disease. The aim of this study was to investigate the drug's effect on cardiac repolarization and sinus autonomic and vascular control in men with mild chronic heart failure (CHF; New York Heart Association classification II). Changes in these variables could predispose patients to malignant ventricular arrhythmias. METHOD: We measured QT dispersion, the QT-RR slope, and the index of QT variability (QTVI) and analyzed spectral power of RR and systolic blood pressure variability in 10 men with dilated cardiomyopathy and in 10 control subjects after administration of a single 50-mg oral dose of sildenafil citrate or placebo at rest (not followed with any attempt at intercourse). RESULTS: In both groups, oral sildenafil citrate decreased the systolic blood pressure (P <.05) and increased the heart rate (P <.05). In subjects with CHF, it also increased the QT-RR (P <.001) and QTVI (from -0.45 +/- 0.07 to -0.27 +/- 0.07; P <.001), but in controls, it increased the QTVI (from -1.20 +/- 0.08 to -0.78 +/-.014; P <.001). In these subjects and controls, oral sildenafil citrate induced a significant reduction in high frequency, expressed in absolute power (subjects with CHF: from 4.04 +/- 0.14 to 3.43 +/- 0.16 natural logarithm ms2; P <.001; controls: from 5.61 +/- 0.44 to 4.98 +/- 0.32 natural logarithm ms2; P <.05) and in normalized units (P <.05). In subjects with CHF but not in controls, it also significantly increased the low frequency to high frequency ratio (from 1.3 +/- 0.12 to 1.89 +/- 0.16; P <.001) and low frequency expressed in normalized units (P <.05). Sildenafil citrate caused no significant changes in the QT interval or dispersion. CONCLUSION: These findings indicate that, in men with heart failure, sildenafil citrate reduces vagal modulation and increases sympathetic modulation, probably through its reflex vasodilatory action. The autonomic system changes induced with sildenafil citrate could alter QT dynamics. Both changes could favor the onset of lethal ventricular arrhythmias. At the dose usually taken for erectile dysfunction, sildenafil citrate has no direct effect on cardiac repolarization (QT interval or dispersion). Am Heart J 2002 Apr;143(4):703-10 QT-interval variability and autonomic control in hypertensive subjects with left ventricular hypertrophy. PICCIRILLO G, GERMANO G, QUAGLIONE R, NOCCO M, LINTAS F, LIONETTI M, MOISE A, RAGAZZO M, MARIGLIANO V, CACCIAFESTA M Left ventricular hypertrophy is a risk factor for sudden death. Malignant ventricular arrhythmias originate from altered cardiac repolarization. Ample data have described spatial abnormalities in cardiac repolarization [QT interval (QT) dispersion] in subjects with hypertension; more data are needed on temporal changes. This study was designed to assess the QT variability index (QTVI), the slope between QT and the RR interval (QT-RR(slope)) and spectral QT variability in subjects with arterial hypertension. The results were compared with those from a population at high risk of sudden death, i.e. patients with hypertrophic cardiomyopathy (HCM) who had received an implantable cardioverter/defibrillator (ICD), and those from normotensive control subjects. A total of 44 hypertensive subjects, six patients with HCM and an ICD and 33 control subjects underwent simultaneous short-term recording (256 beats) of QT, RR and systolic blood pressure variability, in the supine position, during controlled breathing. QTVI and spectral components of QT variability in the hypertensive group were significantly higher than in normotensive control subjects (P<0.001), but significantly lower than in patients with HCM and an ICD (P<0.001). The severity of left ventricular hypertrophy correlated significantly with QTVI and the ratio of low-frequency (LF) to high-frequency (HF) power obtained from the RR variability spectra (RR(LF/HF), slope=0.24, P<0.05; QTVI, slope=4.06, P<0.0001; intercept, slope=2.40, P<0.05; chi(2)=38.8; P<0.0001). The QT--RR slope was significantly higher only in patients with HCM and an ICD (P<0.001). In conclusion, the increased QTVI and the correlation of this index with left ventricular hypertrophy indicates that hypertension increases temporal cardiac repolarization abnormalities. At the level of the cardiac sinus node, this alteration is associated with increased sympathetic and reduced vagal modulation. As already noted in patients with HCM, the increased QTVI could be a factor responsible for triggering malignant ventricular arrhythmias in subjects with hypertension. Clin Sci (Lond) 2002 Mar;102(3):363-71 Influence of age, the autonomic nervous system and anxiety on QT-interval variability. PICCIRILLO G, CACCIAFESTA M, LIONETTI M, NOCCO M, DI GIUSEPPE V, MOISE A, NASO C, MARIGLIANO V As QT variability increases and heart rate variability diminishes, the QT variability index (QTVI) - a non-invasive measure of beat-to-beat fluctuations in QT interval on a single ECG lead - shows a trend towards positive values. Increased QT variability is a risk factor for sudden death. Aging lengthens the QT interval and reduces RR-interval variability. In the present study we investigated the influence of aging and the autonomic nervous system on QT-interval variability in healthy subjects. We studied 143 healthy subjects, and divided them into two age ranges (younger and older than 65 years). For each subject we measured two QTVIs: from the q wave to the end of the T wave (QTeVI) and to the apex of the T wave (QTaVI). Both indexes were calculated at baseline and after sympathetic stress. In 10 non-elderly subjects, both QTVIs were determined after beta-adrenoreceptor blockade induced by intravenous infusion of propranolol or sotalol. The QTVI was higher in elderly than in younger subjects (P<0.001). QTVIs obtained during sympathetic stress remained unchanged in the elderly, but became more negative in the younger group (P<0.05). QTeVI and QTaVI at baseline were correlated positively with age (P<0.01) and anxiety scores (P<0.05), but inversely with the low-frequency spectral power of RR-interval variability (P<0.001). QTVIs were higher in subjects with higher anxiety scores. In younger subjects, sotalol infusion increased both QTVIs significantly, whereas propranolol infusion did not. In conclusion, aging increases QT-interval variability. Whether this change is associated with an increased risk of sudden death remains unclear. The association of abnormal QT-interval variability with anxiety and with reduced low-frequency spectral power of heart rate variability merits specific investigation. In healthy non-elderly subjects, acute sympathetic stress (tilt) decreases the QTVI. beta-Adrenoreceptor blockade inhibits this negative trend, thus showing its sympathetic origin. Because a negative trend in QTVI induced by sympathetic stress increases only in younger subjects, it could represent a protective mechanism that is lost with aging. Clin Sci (Lond) 2001 Oct;101(4):429-38 Influence of aging and other cardiovascular risk factors on baroreflex sensitivity. PICCIRILLO G, DI GIUSEPPE V, NOCCO M, LIONETTI M, MOISE A, NASO C, TALLARICO D, MARIGLIANO V, CACCIAFESTA M OBJECTIVES: To examine the influence of known cardiovascular risk factors (cholesterol, blood glucose levels, arterial pressures, heart rate, and aging) on baroreflex sensitivity. DESIGN: An observational epidemiological study. SETTING: Geriatric Division at the Policlinico Umberto Primo, University of Rome La Sapienza. PARTICIPANTS: Two hundred three subjects whose ages ranged from 9 to 94 years, apparently healthy and free of detectable clinical evidence of atherosclerosis. MEASUREMENTS: All subjects underwent determination of baroreflex sensitivity by phenylephrine infusion (BSphe), and by a noninvasive method derived from spectral analysis of R-R interval and arterial pressure variabilities (alpha index). RESULTS: The population, subdivided into tertiles for each variable studied, had lower BSphe values and lower alpha indexes as a function of age, plasma low-density lipoprotein (LDL) cholesterol, and systolic blood pressure. The alpha index was significantly lower in both groups with elevated LDL cholesterol levels than in those with lower levels (II and III vs I tertile, P <.001), whereas BSphe differed significantly only in the two groups who had extreme levels of LDL (I vs III tertile, P <.001). Multiple regression analysis identified a negative association of the alpha index with age (P <.001), heart rate (P <.01), area under the glucose-response curve (P <.001), and LDL cholesterol (P <.01), but of BSphe only with age (P <.001) and heart rate (P <.01). CONCLUSION: These findings indicate that some risk factors for coronary heart disease adversely influence baroreflex sensitivity. J Am Geriatr Soc 2001 Aug;49(8):1059-65 Influence of aging on cardiac baroreflex sensitivity determined non-invasively by power spectral analysis. PICCIRILLO G, CACCIAFESTA M, VIOLA E, SANTAGADA E, NOCCO M, LIONETTI M, BUCCA C, MOISE A, TARANTINI S, MARIGLIANO V Aging reduces cardiac baroreflex sensitivity. Our primary aim in the present study was to assess the effects of aging on cardiac baroreflex sensitivity, as determined by power spectral analysis (alpha index), in a large population of healthy subjects. We also compared the alpha indexes determined by power spectral analysis with cardiac baroreflex sensitivity measured by the phenylephrine method (BS(phen)). We studied 142 subjects (79 males/63 females; age range 9-94 years), who were subdivided into five groups according to percentiles of age (25, 50, 75 and 95). Power spectral analysis yields three alpha indexes: an alpha low-frequency (LF) index of cardiac baroreflex sensitivity that ranges around 0.1 Hz; an alpha high-frequency (HF) index reflecting cardiac baroreflex sensitivity corresponding to the respiratory rate; and alpha total frequency (alpha TF), a new index whose spectral window includes all power in the range 0.03-0.42 Hz. Spectra were recorded during controlled and uncontrolled respiration. Under both conditions, all three alpha indexes were higher in the youngest age group (< or =34 years old) than in the three oldest groups. Notably, alpha TF was significantly higher in younger subjects than in the three oldest groups [14+/-1 ms/mmHg compared with 9+/-1 (P<0.05), 8.1+/-1 (P<0.001) and 8.1+/-1 (P<0.05) ms/mmHg respectively]. BS(phen) showed a similar pattern [12+/-1 ms/mmHg compared with 8+/-0.5 (P<0.001), 6+/-0.5 (P<0.05) and 6+/-1 (P<0.05) ms/mmHg respectively]. No significant differences were found for cardiac baroreflex sensitivity among the three oldest groups. All alpha indexes were correlated inversely with age. The index yielding the closest correlation with BS(phen) was alpha TF (r=0.81, P<0.001). Cardiac baroreflex sensitivity in normotensive individuals declines with age. It falls predominantly in middle age (from approx. 48 years onwards) and remains substantially unchanged thereafter. The elderly subjects we selected for this study probably had greater resistance to cardiovascular disease that is manifested clinically, with preserved cardiac baroreceptor sensitivity Clin Sci (Lond) 2001 Mar;100(3):267-74 Effects of carvedilol on heart rate and blood pressure variability in subjects with chronic heart failure. PICCIRILLO G, LUPARINI RL, CELLI V, MOISE A, LIONETTI M, MARIGLIANO V, CACCIAFESTA M In this study we observed that carvedilol administration to patients with heart failure improves hemodynamic function, baroreflex sensitivity, and heart rate variability. These findings contribute to improvement in survival in such patients. Am J Cardiol 2000 Dec 15;86(12):1392-5, A6 Autonomic modulation of heart rate and blood pressure in normotensive offspring of hypertensive subjects. PICCIRILLO G, VIOLA E, NOCCO M, DURANTE M, TARANTINI S, MARIGLIANO V Predominant sympathetic cardiovascular modulation in the hyperkinetic phase of arterial hypertension has been well described. Less information is available on autonomic control in persons with a family history of arterial hypertension. To investigate this question, we selected 61 normotensive subjects (mean age 30.9 +/- 1.8 years) whose mother or father or both had arterial hypertension and 30 normotensive patients (mean age 30.1 +/- 1.4 years) whose parents had not had arterial hypertension (neither mother nor father) to undergo short-term power spectral analysis of RR interval and arterial pressure variabilities. The same recordings were used to determine baroreflex sensitivity or the alpha index by means of the transfer function. Normotensive offspring of hypertensive subjects had higher diastolic blood pressures (P < .05) and left ventricular mass index (P < .05) than did normotensive offspring of non-hypertensive subjects. They also had higher spectral densities of low frequency expressed in normalized units, both for R-R intervals (P < .05) and systolic pressure variabilities (P < .05); they also had a greater ratio of low-frequency to high-frequency powers of R-R interval variability (P < .05). No difference was observed between the two normotensive groups for baroreflex sensitivity. Our spectral data indicate that normotensive persons with a positive family history of arterial hypertension have lower parasympathetic modulation than those with a negative history. In normotensive persons with a family history of arterial hypertension, normal baroreflex sensitivity could be the mechanism that buffers the tendency for pressures to increase. The gradual loss of this regulatory mechanism may favor rising arterial pressures. J Lab Clin Med 2000 Feb;135(2):145-52 Autonomic modulation and QT interval dispersion in hypertensive subjects with anxiety. PICCIRILLO G, VIOLA E, NOCCO M, SANTAGADA E, DURANTE M, BUCCA C, MARIGLIANO V 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. Hypertension 1999 Aug;34(2):242-6 QT interval dispersion and autonomic modulation in subjects with anxiety. PICCIRILLO G, VIOLA E, BUCCA C, SANTAGADA E, RAGANATO P, TONDO A, LUCCHETTI D, NOCCO M, MARIGLIANO V 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. J Lab Clin Med 1999 May;133(5):461-8 Heart rate and blood pressure variability in obese normotensive subjects. PICCIRILLO G, VETTA F, VIOLA E, SANTAGADA E, RONZONI S, CACCIAFESTA M, MARIGLIANO V OBJECTIVE: To assess autonomic modulation of cardiovascular activity in massively obese subjects. DESIGN: Cross-sectional clinical study. SUBJECTS: 43 age-matched normotensive subjects: 15 moderately obese (body mass index (BMI) < 40); 14 massively obese (BMI > 40) and 14 nonobese controls (BMI < 26). MEASUREMENTS: Using power spectral analysis, heart rate and arterial pressure variability were determined at rest and after sympathetic stress (tilt). Two spectral components were analysed: a low-frequency (LF) component at around 0.1 Hz, predominantly reflecting sympathetic modulation and a high-frequency (HF) component at around 0.26 Hz, reflecting parasympathetic modulation. RESULTS: Spectral data for heart rate showed that the massively obese subjects had lower LF [mean +/- s.e.m.] normalized units (NUs) at rest (35.1 +/- 0.9) and after tilt (56.1 +/- 2.1), than the moderately obese subjects (LF NUs at rest 53.9 +/- 4.2, P < 0.001; LF NUs tilt: 66.8 +/- 5.6, P < 0.001) and nonobese control subjects (LF NUs at rest, 56.6 +/- 3.0, P < 0.001); (LF NUs tilt: 81.7 +/- 1.7, P < 0.001). Data for systolic arterial pressure variability measured at rest exhibited the inverse pattern, the massively obese group having higher mean LF values (LF mm Hg2 rest: 15.0 +/- 1.4; LF mm Hg2 tilt: 15.7 +/- 1.5) than the moderately obese group (LF mm Hg2 rest 3.2 +/- 0.7, P < 0.001; LF mm Hg2 tilt: 7.2 +/- 2.0, P < 0.001) and than the nonobese control subjects (LF mm Hg2 rest 3.5 +/- 0.5, LF mm Hg2 tilt 8.5 +/- 0.8, P < 0.001). Regression detected a significant association between BMI and LF of systolic pressure (beta = 0.364; P = 0.0007), In LF of heart rate (beta = -5.555; P = 0.00001) and very low frequency (VLF) of diastolic pressure (beta = -3.305; P = 0.0020). CONCLUSION: Obesity seems to increase sympathetic modulation of arterial pressure, but diminishes modulation of heart rate. Because our obese subjects had high plasma noradrenaline levels, their low LF power of heart rate could reflect diminished adrenoceptor responsiveness. Int J Obes Relat Metab Disord 1998 Aug;22(8):741-50 Autonomic modulation of heart rate and blood pressure in hypertensive subjects with symptoms of anxiety. PICCIRILLO G, ELVIRA S, VIOLA E, BUCCA C, DURANTE M, RAGANATO P, MARIGLIANO V 1. The influence of anxiety symptoms on autonomic nervous system cardiovascular control has never been studied in hypertensive subjects. This study was designed to verify the presence of sympathetic hyperactivity in hypertension associated with anxiety symptoms. 2. Neuroautonomic cardiovascular control was evaluated using short-time power spectral analysis of RR and arterial pressure variability at baseline and after the head-up tilt test. The two spectral components principally influenced by the autonomic nervous system are the low-frequency (LF) component, mainly though not exclusively due to sympathetic modulation, and the high-frequency (HF) component, due to parasympathetic activity. The ratio of LF to HF powers (LF:HF) provides an index of the sympathovagal sinus balance. 3. We studied 33 hypertensive subjects (mean age 47+/-1 years; M:F=19:14) and 37 normotensive control subjects (mean age: 47+/-2 years; M:F=20:17) divided into four subgroups: hypertensive subjects who scored 2 or more on a 5-item anxiety symptom scale, hypertensive subjects who scored 0, normotensive controls who scored 2 or more and normotensive controls who scored 0. LF:HF and LF during rest were significantly higher (P<0.05) in hypertensive and normotensive groups with an anxiety score of 2 or more compared with the two groups who scored 0. HF of systolic blood pressure was significantly lower in the hypertensive group who scored 2 or more than in the hypertensive group who scored 0 (P<0.05). Tilt in both hypertensive groups reporting anxiety symptoms left the indexes of sympathetic modulation unchanged. Tilt in hypertensive subjects reporting anxiety symptoms also induced a significant fall in arterial pressure (P<0.05). The mean left ventricular mass index was significantly higher in the hypertensive subjects who had anxiety scores of 2 or more than in those scoring 0 (144.7+/-3.0 versus 133. 4+/-2.31, P<0.05). 4. In conclusion, normotensive and hypertensive subjects reporting anxiety symptoms showed increased sympathetic modulation of heart rate at rest. Higher anxiety scores seem to be associated with the development of left ventricular hypertrophy. Clin Sci (Lond) 1998 Jul;95(1):43-52 Power spectral analysis of heart rate in subjects over a hundred years old. Piccirillo G, Bucca C, Bauco C, Cinti AM, Michele D, Fimognari FL, Cacciafesta M, Marigliano V 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. Int J Cardiol 1998 Jan 5;63(1):53-61 Abnormal passive head-up tilt test in subjects with symptoms of anxiety power spectral analysis study of heart rate and blood pressure. PICCIRILLO G, ELVIRA S, BUCCA C, VIOLA E, CACCIAFESTA M, MARIGLIANO V 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. Int J Cardiol 1997 Jul 25;60(2):121-31 Heart rate and blood pressure variabilities in salt-sensitive hypertension. Piccirillo G, Bucca C, Durante M, Santagada E, Munizzi MR, Cacciafesta M, Marigliano V 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. Hypertension 1996 Dec;28(6):944-52 Power spectral analysis of heart rate variability in obese subjects: evidence of decreased cardiac sympathetic responsiveness. Piccirillo G, Vetta F, Fimognari FL, Ronzoni S, Lama J, Cacciafesta M, Marigliano V OBJECTIVE: To investigate changes in sympathetic nervous system function in obesity. DESIGN: Cross-sectional clinical study. SUBJECTS: 18 middle-aged obese patients (43-55 years, BMI > 33 kg/m2) and 26 age- and sex-matched normal-weight controls (44-56 years, BMI < 26 kg/m2). MEASUREMENTS: Post-synaptic sympathetic response studied by power spectral analysis of heart rate variability at rest and during sympathetic stimulus obtained through passive head-up tilt. Spectral analysis comprised two frequency domain components: high-frequency power (HF), reflecting parasympathetic activity and low-frequency power (LF), in particular the LF: HF ratio, reflecting sympathetic function. Pre-synaptic sympatho-adrenal function was assessed by measurement of 8.00 am plasma noradrenaline. RESULTS: Obese patients had significantly lower spectral indexes of sympathetic response and higher spectral markers of parasympathetic activity than nonobese subjects both at rest (25.9 +/- 3.5 vs 38.6 +/- 1.7 LF NUs, P < 0.001) and after tilt (0.98 +/- 0.40 vs 2.30 +/- 0.39 LF: HF, P < 0.05; 62.7 +/- 6.9 vs 41.1 +/- 4.9 HF NUs, P < 0.05). By contrast, the obese subjects had higher noradrenaline levels (289.32 +/- 27.40 vs 159.80 +/- 19.20 pg/ml, P < 0.001). No relation was found between these neuroautonomic indexes and body mass index. CONCLUSION: Obese subjects seem to have increased pre-synaptic sympatho-adrenal function but a depressed end-organ cardiovascular response. Int J Obes Relat Metab Disord 1996 Sep;20(9):825-9 Age-dependent influence on heart rate variability in salt-sensitive hypertensive subjects. Piccirillo G, Fimognari FL, Munizzi MR, Bucca C, Cacciafesta M, Marigliano V 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. DESIGN: In a randomized study, autonomic nervous system function was assessed by power spectral analysis of heart-rate variability calculated with an autoregressive algorithm in salt-sensitive hypertensives and controls at baseline and under sympathetic stress (passive head-up tilt). For 1 week before the study, all subjects kept to a diet supplying 120 mEq sodium. Sodium sensitivity was assessed by measuring and comparing arterial pressures after a 7-day controlled dietary sodium intake of 20 mEq per day after a 7-day period on 220 mEq sodium/day. SETTING: Geriatric division at the I Medical Clinic of the University of Rome "La Sapienza". PARTICIPANTS: Sixty-five patients with salt-sensitive hypertension (age range 19 to 89 years) and 64 age-matched normotensive controls, divided for data comparison into three age-groups: < 44 years; 44 to 64 years; and > or = 65 years. MEASUREMENTS: With an autoregressive algorithm in a power spectral analysis of heart rate variability, we detected four spectral frequency-domains: total power (0.0033 to 0.40 Hz), high-frequency power (0.16 to 0.40 Hz), low-frequency power (0.04 to 0.15 HZ) and very-low-frequency power (0.0033 to 0.04 Hz). To determine sodium sensitivity, for 1 week before the study all subjects kept to a diet supplying 120 mEq sodium. Sodium sensitivity was assessed by measuring and comparing arterial pressures after a 7-day controlled dietary intake of 20 mEq per day and after a 7-day period of 220 mEq sodium/day. RESULTS: Results were expressed as natural logarithms of power and normalized units. The hypertensive patients of all ages had significantly lower total power of heart rate variability than the normotensive controls (P < .05). At baseline, the youngest hypertensives had lower natural logarithms and low-frequency normalized units than controls (P < .001). After tilt, only their low-frequency normalized units exceeded those of controls (P < .001). The middle-aged hypertensive group had higher low-frequency normalized units than controls at baseline (P < .05) and after tilt (P < .001). At baseline and after tilt, the oldest hypertensives had lower low-frequency natural logarithms than controls (P < .05) and normalized units equal to those of controls. But the hypertensives of all ages were less able than controls (P < .001) to increase low-frequency power after head-up tilt. In the less than 44-year-old hypertensives, diastolic pressure correlated significantly with low-frequency power of heart rate variability, expressed in normalized units, at baseline (P < .05) and after head-tilt (P < .05). A significant inverse correlation was found between age and the natural logarithm of low-frequency power at baseline (r = -.682, P < .001) and after tilt (r = -.800; P < .001). Also, a significant inverse correlation was found to exist in normotensive subjects between the natural logarithm of low-frequency at baseline (r = -.595; P < .001) and after tilt (r = -.391; P < .001). The two regression line coefficients for age correlated significantly (P < .001) with the natural logarithm of low-power frequency after tilt. CONCLUSION: Whereas sodium chloride-sensitive hypertension appears to be associated with sympathetic hyperactivity in young and middle-aged subjects, in older people it is not. Sympathetic activity diminishes with age, declining faster in hypertensive subjects. J Am Geriatr Soc 1996 May;44(5):530-8 Heart rate variability in hypertensive subjects. PICCIRILLO G, MUNIZZI MR, FIMOGNARI FL, MARIGLIANO V 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. Int J Cardiol 1996 Mar;53(3):291-8 Power spectral analysis of heart rate in elderly hypertensive subjects with or without silent coronary disease. PICCIRILLO G, FIMOGNARI FL, SANTAGADA E, MUNIZZI MR, VIOLA E, MONTEFORTE G, BUCCA C, DURANTE M, DI GIOACCHINO C, TARANTINI S, LO VERDE A, CACCIAFESTA M, MARIGLIANO V Much evidence indicates an involvement of the sympathetic nervous system in the genesis of silent myocardial ischemia. The authors assessed autonomic system activity by power spectrum analysis of heart rate variability in 21 elderly hypertensive men with and without angiographically confirmed coronary artery disease and compared the results with those from an age-matched control group. In the analysis an autoregressive algorithm was used to determine the power spectrum from an electrocardiographic recording of 512 consecutive RR intervals. The autonomic nervous system induces two distinct sinusoids: a low-frequency signal attributable to sympathetic activity and a high-frequency vagal response. In the hypertensive patients with coronary disease the authors also evaluated sympathetic activation after double-blind, placebo-controlled administration of metoprolol (100 mg/day), followed by amlodipine (10 mg/day), quinapril (20 mg/day), and amlodipine (5 mg/day) plus quinapril (10 mg/day). Angiology 1996 Jan;47(1):15-22 Age-adjusted normal confidence intervals for heart rate variability in healthy subjects during head-up tilt. PICCIRILLO G, FIMOGNARI FL, VIOLA E, MARIGLIANO V PURPOSE: Aging 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. PATIENTS AND METHODS: In 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. RESULTS: For 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). CONCLUSION: The 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. Int J Cardiol 1995 Jun 30;50(2):117-24 Effects of phlebotomy on a patient with secondary polycythemia and angina pectoris. PICCIRILLO G, FIMOGNARI FL, VALDIVIA JL, MARIGLIANO V A 67-year-old man with polycythemia, secondary to chronic obstructive pulmonary disease, had angina attacks at rest treated successfully by supplementing conventional therapy with frequent phlebotomies. Although phlebotomy reduces arterial oxygen content, it also decreases blood viscosity, improves peripheral oxygen consumption and thus yields the clinical benefit. Int J Cardiol 1994 Apr;44(2):175-7 High plasma concentrations of cortisol and thromboxane B2 in patients with depression. PICCIRILLO G, FIMOGNARI FL, INFANTINO V, MONTELEONE G, FIMOGNARI GB, FALLETTI D, MARIGLIANO V Modulation of the hypothalamic-pituitary-adrenal axis in major depression is thought to depend on the hypothalamus and other areas of the central nervous system, or both. Hypothalamic over-activity may be responsible for the hypercortisolism observed in 50% of depressed subjects. To investigate the relation between psychosocial factors and cardiovascular disease, morning (8 AM) plasma concentrations of cortisol and thromboxane B2 (the stable metabolite of thromboxane A2, an eicosanoid closely linked to thrombotic disorders) were measured by radioimmunoassay in 32 patients with major depression (DSM III) triggered by psychosocial events and in 9 nondepressed volunteers. The depressed patients were studied in two groups, 16 with cortisol levels under 90 ng/mL and 16 with levels over 90 ng/mL. All the healthy non-depressed subjects had cortisol values over 100 ng/mL. The depressed patients with high cortisol had significantly higher plasma TxB2 concentrations than the other two groups. In addition, plasma cortisol and TxB2 concentrations correlated significantly over the whole group of depressed patients and in the high cortisol sub-group but not in the low-cortisol sub-group or in the nondepressed subjects. These findings appear to support the recently proposed role of the hypothalamic dysfunction associated with affective disorders in the pathogenesis of cardiovascular disease. Am J Med Sci 1994 Mar;307(3):228-32
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