ATTIVITA' EDITORIALE -Argomenti di Geriatria -End-organ Damage:... -Invecchiare bene... -Stress, invecchiamento ... -Invecchiamento e Longevità -Motricità Invecchiamento... PUBBLICAZIONI -PROF. MARIGLIANO -PROF. A.AMICI -PROF P. CICCONETTI -PROF. E. ETTORRE -PROF M. GNECCHI -PROF N.GUELI -PROF G.PICCIRILLO -PROF. G.E.RUSSO -PROF. G.TROISI BANDO STUDENTI

PROF. MARIGLIANO Principali pubblicazioni degli ultimi anni Prof. V.MARIGLIANO MARIGLIANO V., CAMPANA F., BAUCO C., ETTORRE E., CICCONETTI P., TRIVELLA P. Health and longevity. RECENT ADVANCES IN AGING SCIENCE 1423-26, Monduzzi ed.1993. SCUTERI A., CACCIAFESTA M., DI BERNARDO M.G., DE PROPRIS A.M., DEL FOCO C., CICCONETTI P., MARIGLIANO V. For the management of cardiovascular risk in the elderly: which markers? RECENT ADVANCES IN AGING SCIENCE 997-999, 1993 SCUTERI A., CACCIAFESTA M., DI BERNARDO M.G., DE PROPRIS A.M., DEL FOCO C., CICCONETTI P., MARIGLIANO V. Mean platelet volume and its prognostic relevance in elderly hypertensives. RECENT ADVANCES IN AGING SCIENCE 959-961, 1993 PICCIRILLO G., BUCCA C., FIMOGNARI F.L., DI DOMENICO C., PALLESCHI L., CICCONETTI P., MARIGLIANO V. Beta-adrenoceptors sensitivity in elderly with unstable angina and silent ischemia. RECENT ADVANCES IN AGING SCIENCE 1011-1014, 1993 MARIGLIANO V., CICCONETTI P., FERRI C., GIANNI W., VETTA F. Ipertensione arteriosa in et? senile: fattore di rischio e fattori di rischio. GIORNALE ITALIANO DI GERONTOLOGIA VOL. 41: 573-582, 1993 SCUTERI A., CACCIAFESTA M., DI BERNARDO M.G., DE PROPRIS A.M., RECCHI D., CELLI V., CICCONETTI P., MARIGLIANO V. Pulsatile versus steady-state component of blood pressure in elderly females: an indipendent risk factor for cardiovascular disease? Objective: To evaluate whether the pulsatile component of blood pressure can be a risk factor independent of the steady component in elderly females. Design: Fifty-two elderly hypertensive female patients were compared with 32 normotensive contro] subjects of the same age. According to the results of that first study, a cohort of 126 elderly females was studied over a 3-year period to evaluate whether the pulsatile and steady-state components of blood pressure correla,tecl with the same parameters and could predict the occurrence of cardiovascular events. Results: In the first study the hypertensive patients with elevated pulse pressure had significanfly higher triglycerides level and lower urinary sodium excretion than the hypertensive patients with lower pulse pressure and than the control subjects of the same age. The incidence of cardiovascular events over a 3-year period was sign?ficantiy higher in the eldefly hypertensive females with increased pulse pressure. In the cohort of 126 females mean arterial pressure (MAP) and pulse pressure did not show the same degree of correlation with the biological parameters tested (plasma triglycerides: MAP r=0.162, P<0.05; pulse pressure r=0.314, P<0.0005; urinary sodium excretion: MAP r=-0.365, P<0.0001; pulse pressure r=-0.257, P<0.002). Furthermore, for the same MAP level, patients with cardiovascular accidents in a 3-year period hacI significantly higher pulse pressure values. Pulse pressure (and not MAP) was a strong pred?ctor of cardiovascular accidents. Conclusions: in elderly hypertensive females the pulsatile and the steady-state components of blood pressure did not correiate with the same biological parameters. Furthermore, the pulsatile component, when explored by pulse pressure, seemed to be a strong independent cardiovascular risk factor. J. HYPERTENSION 13: 185-191, 1995 VETTA F., RONZONI S., PALLESCHI L., MIGLIORI M., LUPATTELLI M.R., CICCONETTI P., MARIGLIANO V. I lipidi nell'alimentazione dell'anziano. ALIMENTAZIONE, NUTRIZIONE E METABOLISMO vol. 17, pg 125-132, 1996. BAUCO C., GOLOSIO F., CINTI A.M., BORRIELLO C., RAGANATO P., CICCONETTI P., MARIGLIANO V. Functional status and well being of centenarians. Data regarding a sample of 109 centenarians are presented, living in the region of central Italy. Physical and psychosocial variables were analyzed by a questionnaire based on a multidimensional conceptualization of health. Objective and laboratory data were collected and functional capacity was complemented by clinical diagnoses and judgements as well as by self-reported health problems and functional limitations. The results reveal that people can reach their maximum life span while maintaining good levels of functional capacity in spite of the chronological age. One major aspect of functional status in upper ranges of human life span is the everyday competence in the activities of daily living (ADL). In this regard, 26.6 % of centenarians are classified as having no ADL-dependency (level A: 34.6 % of males and 24.0 % of females); the most frequent type of dependency was in bathing (65.1 %; 46.2 % of males, 71.1 % of females) and in continence (45.9 %; 50 % of males, 44.6 % of females). The Mini Mental State Examination (MMSE) showed a mean score of 19.86 5.93 (21.04 5.33 of males; 19.49 6.10 of females). The Geriatric Depression Scale (GDS) mean score was 8.22 4.89 (7.60 5.05 of males, 8.40 4.87 of females). Keywords: centenarians, activities of daily living, mini mental state examination, geriatric depression scale ARC. GERONTOL.GERIATR., suppl. 5, pg 363-366, 1996. RIZZO V., CICCONETTI P., BIANCHI A., LORIDO A., MORELLI S., VETTA F., SALZA M.C., MARIGLIANO V. White-coat hypertension and cardiac organ damage in elderly subjects. Purpose: The aim of this study was comparing the cardiac mass in elderly normotensive subjects and elderly white coat hypertensive patients by examining in perspective, in consecutive patients, office blood pressure (BP), ambulatory BP, and echocardiographically determined justify ventricular mass. Patients and methods: We studied 42 elderly patients attending a hypertension unit: of these, 22 (mean age 68.7 ± 3.2 years) had persistent >9O mm Hg office diastolic blood pressure (DBP), >140 mm Hg systolic blood pressure (SBP) and < 142/90 mm Hg daytime ambulatory BP (white coat positives); the remaining 20 (mean age 67.4±2.2 years) had <90 mmHg office DBP, <140 mmHg SBP and <142/90 mmHg daytime ambulatory BP (normotensives). White coat patients (n=22) were selected from a series of 75 consecutive newly diagnosed and never treated patients with mild hypertension (casual DBP constantly between 90 mm Hg and 105 mm Hg). Results: Neither justify ventricular mass index (89.9 ± 23.1 vs 91 .8 ± 25.4 P = NS and ± 25.4 P = NS) and justify ventricular mass/height, (115.4 ± 17.1 vs 119.6 ± 18.3 P= NS), nor relative wall thickness (0.31 ± 0.44 vs 0.33 ± 0.05 P= NS) were significantly higher in white coat hypertensives as against normotensives. Neither did we find a relevant difference between justify atrial diameters In the above considered groups (3.28 ± 0.41 vs 3.32 ± 0.37). In fact 81.8% of white coat hypertensives had justify ventricular normal geometry; whilst 13.6% only had concentric remodeling. Age and sex were associated with justify ventricular mass index, justify ventricular mass/height and relative wall thickness. Multiple regression analysis revealed that it is ambulatory, not office BP that carries independent information about relative wall thickness and justify ventricular mass indices. Conclusions: Since elderly white coat hypertensive subjects did not display a greater cardiac involvement than age matched normotensives, they should be treated as such. J. HUM. HYPERTENSION, vol. 10, n.5: 293-298, 1996. CICCONETTI P., SALZA M.C., RIZZO V., MARIGLIANO V. Correlazioni tra variabilit? pressoria e diversi indici di massa ventricolare sinistra in soggetti anziani ipertesi e normotesi. CARDIOLOGIA EXTRA OSPEDALIERA, , vol 2, n.2, pg 144-146, 1996. CICCONETTI P., SALZA M.C., RIZZO V., BIANCHI A., CAPPONI L., MARIGLIANO V. Rapporto valle/picco e variabilit? pressoria durante terapia con Fosinopril in pazienti anziani ipertesi. LA CLINICA TERAPEUTICA, vol. 147, fasc. 7-8: 359-364, luglio-agosto 1996. RIZZO V., PICCIRILLO G., CICCONETTI P., BIANCHI A., CAPPONI L., SALZA M.C., CACCIAFESTA M., MARIGLIANO V. Ambulatory blood pressure and echocardiographic justify ventricular dimension in elderly hypertensive subjects. In a consecutive series of 62 hypertensive elderly subjects, the authors studied the relation of blood pressure circadian variations with echocardiographic parameters of justify ventricular (LV) hypertrophy. All the subjects were submitted to an ambulatory blood pressure monitoring (ABPM) and to B- and M-mode echocardiography. In the elderly hypertensive group, LV mass index (LVMI) was more strongly related to twenty-four-hour, daytime and nighttime systolic ambulatory blood pressure (r = 0.52, r = 0.37, r = 0.51) than diastolic ambulatory blood pressures were (r = 0.32, r = 0.18, r = 0.33). Casual systolic and diastolic blood pressure (CBP) was found more weakly related to LVMI than ambulatory blood pressures were (r = 0.35, r = 0.26). Elderly hypertensive subjects were divided into two subgroups in relation to the presence (group 1) or absence (group 2) of blood pressure nocturnal decline. No differences were found between these two subgroups in regard to: casual blood pressure values, ambulatory blood pressures in the diurnal period, sex, body surface area, height, weight, and age. LVMIs were computed in all three groups and showed the following results: 89.32 +/- 19.76 in elderly normotensives, 91.21 +/- 31.32 in group 1, and 99.80 +/- 18.21 in group 2. Echocardiographic parameters of LV dimensions and LVMIs were different in group 1 and 2. An inverse correlation, statistically significant, was observed between LVMIs and the nocturnal blood pressure reduction (systolic: r = -0.36, P < 0.05; diastolic: r = -0.29, P < 0.05). These results suggest an association between a smaller LV mass and nocturnal blood pressure decline in elderly hypertensive patients. ANGIOLOGY, vol. 47, n.10: 981-989, ottobre 1996 . CICCONETTI P., SALZA M.C., THAU F., MARIGLIANO V. Rapporto valle/picco e variabilit? pressoria: nuovi indici di valutazione della terapia con Fosinopril in ipertesi adulti e anziani. Trough.Peak ratio and blood pressure varlability new Indexes for the valutation of therapy with FosInopril in adult and eldedy hyper tensive subjects. Antihypertensive drug therapy uniformity of efficacy was evaluated in a group of adult and in a group of elderly hypertensive subjects with trough to peak ratio, after a period of antihypertensive drug therapy with ACE inhibitor fosinopril. An ambulatory blood pressure monitoring (ABPM) with evaluation of blood pressure variability assessed by standard deviation (S.D.) and coefficient of variation (C.V.) were evaluated In each subject. Our data showed that the treatment with fosinopril had satisfactory uniformity of efficacy during all the 24 hour period in both groups, little influence on blood pressure variability was determ?nated by antihypertens?ve treatment. CARDIOLOGIA EXTRA OSPEDALIERA, vol. 3, n.2, 140-143, 1997. VETTA F., CICCONETTI P., RONZONI S., RIZZO V., PALLESCHI L., CANARILE G., LUPATTELLI M.R., MIGLIORI M., MORELLI S., MARIGLIANO V. Hyperinsulinaemia, regional adipose tissue distribution and justify ventricular mass in normotensive, elderly, obese subjects. Obesity is a metabolic condition, related to abnormalities of the glyco-insulinaemic metabolism, and plays a substantial role in the development of cardiovascular disease. The aim of this study was to establish a correlation among justify ventricular mass, evaluated echocardiographically according to Penn Convention criteria, blood pressure, evaluated by ambulatory blood pressure monitoring, anthropometric indices for evaluation of body mass index and waist to hip ratio circumference, regional adipose tissue distribution, evaluated by ultrasound measurements of visceral adipose tissue, and insulin resistance, evaluated by hyperinsulinaemia by oral glucose tolerance test. We selected two groups of elderly male subjects well matched for age (68.5 +/- 6.4 years): 29 obese and 20 lean, with a body mass index, respectively, of 34.6 +/- 2.9 and 23.4 +/- 2.3. Statistical analysis was carried out by Student's t-test and linear regression analysis. In spite of the fact that statistical analysis showed a higher, though not statistically significant, systolic and diastolic mean blood pressure in the lean subjects, we found an increased justify ventricular mass in obese subjects (P < 0.0001). The area under the insulin curve was higher in obese than in lean subjects (P < 0.0001) while the area under the glucose curve was not significantly different in the two groups. Furthermore, linear regression analysis showed that in obese subjects justify ventricular mass was strictly correlated with visceral adipose tissue (r = 0.607; P < 0.0001) and hyperinsulinaemia (r = 0.615; P < 0.0001). In conclusion, our data suggest that centripetal adipose tissue distribution and hyperinsulinaemia, independent of blood pressure values, are closely correlated with justify ventricular mass. EUROPEAN HEART JOURNAL, vol. 19, 326-331, febbr. 1998. CICCONETTI P., MONTEFORTE G., THAU F., LORIDO A., DURANTE M., PICCIRILLO G., CACCIAFESTA M., MARIGLIANO V. Cognitive assessment in the elderly with new mild systolic hypertension. The goal of this investigation was to assess the early effects of new systolic hypertension on the cognitive function in the elderly. Using clinical measurements of blood pressure (WHO guidelines), 13 elderly normotensive and 13 elderly subjects with new systolic hypertension were selected, because it is more closely associated with cerebral damage. All 26 subjects were submitted to 24 hour ambulatory blood pressure monitoring (ABPM) to confirm the pressure levels revealed using clinical measurements and to exclude the white-coat effect. The cognitive state was evaluated using the mini mental state examination (MMSE), and the acoustic evoked potential were also recorded with the objective of identifying a possible alteration of the cerebral function correlated to hypertensive pathology, not yet evident otherwise. ABPM data reaffirm the high values of systolic pressure in the elderly hypertensives and the cognitive function does not appear altered. In fact, we did not find any statistically significant differences between normotensive elders, neither in MMSE, a broad measure of cognitive functions, nor in the time lag of P300, being an expression of voluntary process of recognition and memorization of target stimuli. Keywords: cognitive assessment, event related potential (ERP), mild systolic hypertension, ambulatory blood pressure monitoring ARCH. GERONTOL. GERIATR., suppl.6, 75-78, 1998. CICCONETTI P., THAU F., BAUCO C., BIANCHI A., FIDENTE D., VETTA F., ETTORRE E., MARIGLIANO V. Psychological assessment in the elderly with new mild systolic hypertension. The aim of this investigation was to assess the anxiety levels and the presence of symptoms of depression in elderly subjects with recently diagnosed mild systolic hypertension. We selected 13 elderly with new systolic hypertension and 13 elderly normotensive subjects; they underwent psychometric tests like state test anxiety inventory (STAI) for anxiety, and geriatric depression scale (GDS) for depression, and 24-hour ambulatory blood pressure monitoring (ABPM) to assess the real pressure values and exclude the white-coat effect. ABPM data reaffirmed the high values of systolic pressure in the elderly hypertensives identified by using clinical measurements, although it excluded the white-coat effect. Our study found significantly higher anxiety levels in the elderly with mild systolic hypertension, while the symptoms of depression are not significantly different from those of elderly normotensives. Keywords: state test anxiety inventory, mild systolic hypertension, geriatric depression scale, 24-hour ambulatory blood pressure monitoring ARCH. GERONTOL. GERIATR., suppl.6, 79-82, 1998. RONZONI S., VETTA F., PALLESCHI L., LUPATTELLI M.R., MIGLIORI M., LATO P.F.A., PAGANICA P., DE GENNARO E., CICCONETTI P., MARIGLIANO V. Subjective hunger sensation: chronotype analysis of obese elderly subjects and controls in relation to affective state. Several studies showed a strict correlation between body weight and emotional state, showing a high prevalence of anxiety and depression in association to modification of hunger sensation. The aim of this study was to identify, analyzing chronotype differences of subjective hunger sensation between elderly obese subjects compared to non-obese eurettic controls, in association with their affective state. Twenty-four obese subjects (14 males and 10 females) of mean age 68.2 ± 2.8 years were included in the study, with body mass index (BMI) _ 30, and 20 subjects (10 males and 10 females) with BMI _ 30, well matched for age, served as controls. The affective state was evaluated by using the geriatric depression scale (GDS) and the state trait anxiety inventory (STAI). The subjective hunger sensation (SHS) was evaluated by an autoevaluation questionnaire consisting of 10 progressive degree (point 1 = absent, point 10 = intolerable) for each daytime hour (from 6 am to 11 pm). Statistical analysis was carried out by the Mann-Whitney U-test and linear regression analysis; a p value less than 0.05 was considered statistically significant. Mean value of subjective hunger sensation was statistically higher in obese subjects than in controls (p = 0.007), and so was also anxiety (p = 0.01) and depression (p = 0.01). Chronotype analysis showed a significant rise of subjective hunger sensation in every postprandial period (p _ 0.005) with no significant differences between the two groups. We found a significant difference in interprandial gradient (ip) higher in obese subjects than in controls (p = 0.001). Our data show that ip is strictly correlated with the level of depression (ip vs GDS: r = 0.910; p = 0.002) and especially with anxiety (ip vs STAI: r = 0.971; p = 0.001). Keywords: obesity, anxiety, depression, hunger sensation, body mass index ARCH. GERONTOL. GERIATR., suppl.6, 451-454, 1998 . VETTA F., RONZONI S., LUPATTELLI M.R., PALLESCHI L., MIGLIORI M., DE GENNARO E., LATO P.F.A., CICCONETTI P., MARIGLIANO V. Metabolic alterations in malnourished, depressed aged subjects. Several studies have focused their attention on metabolic alterations, chiefly cholesterol plasma levels, related to depression, showing contrasting data. The aim of this study was at evaluating the correlation between anthropometric, metabolic parameters and depression in malnourished aged patients. We included 73 elderly subjects (mean age 79.15 ± 15.3; 40 females and 33 males) age- and sex-matched; 48 patients of this pool were malnourished. All subjects underwent a complete anthropometric and biochemical nutritional assessment as well as a psychometric examination, using the mini mental state examination (MMSE), the geriatric depression scale (GDS) and self-sufficiency tests in form of the activity of daily living (ADL) as well as the instrumental for of it (IADL). Student's t test and linear regression analysis were carried out for statistical analysis. Malnourished subjects showed higher values in GDS scores than controls (p = 0.03), without statistically significant differences in the MMSE scores and cholesterol levels of the two groups, while in depressed group we found lower sideremia (p _ 0.0001), higher triglycerides (p _ 0.05), and insulinemia (p _ 0.001) and impaired self sufficiency (p = 0.001). Linear regression analysis showed a strict correlation between GDS and triglycerides (r = 0.387, p = 0.03), centripetal adipose tissue distribution parameters (r = 0.678, p _ 0.0001), triceps skinfold (r = 0.473, p = 0.008) and sideremia (r = _0.538, p = 0.001). Our data suggest that depression is closely related to malnutrition and to ensuing metabolic alterations, too. The direct correlation between GDS scores and metabolic disorders in these patients can be explained by previous reports supporting the hypothesis that cytokines could have a primary role both in malnutrition and in affective disorders. Keywords: depression in aging, nutritional state and depression, metabolic disorders in depression ARCH. GERONTOL. GERIATR., suppl.6, 525-530, 1998. CICCONETTI P., MIGLIORI M., DI GIOACCHINO C.F., RONZONI S., MARIGLIANO V. Variabilit? pressoria. Ruolo dell'et? e differenze tra sessi. Scopo dello studio ? stato verificare, in soggetti ipertesi, la presenza di modificazioni correlate con l'et? e con il sesso, della variabilit? della pressione arteriosa delle 24 ore; la scelta di un campione diviso per fasce d? et? e con uguale distribuzione dei due sessi ha consentito di valutare il comportamento della variabilit? pressoria, anche in base alle modificazioni dell'assetto ormonale della donna in menopausa. Tutti i soggetti, ipertesi, sono stati sottoposti a monitoraggio ambulatoriale delle 24 ore della pressione arteriosa dal quale sono stati ottenuti due indici di variabilit?: deviazione standard (DS) e coefficiente di variazione (CV). I nostri risultati hanno confermato l'incremento di oscillazioni pressorie con l'et? negli individui ipertesi di entrambi i sessi, svelando inoltre due differenti modalit? di presentazione: nell'uomo una stretta correlazione con l'et? e nella donna una correlazione con l'avanzare dell'et?, forse modulata anche da fattori et? indipendenti. CARDIOLOGIA EXTRAOSPEDALIERA, vol. 4, n.4, pg 388-394, dic. 1998. MARIGLIANO V., CICCONETTI P., SCUTERI A. Arterial Hypertension in the elderly. CLINICAL CASES IN HYPERTENSION: SPECIFIC TREATMENT STRATEGIES. Editor: P. Sleight, pg 149-152. 1998. Cicconetti P., Di Gioacchino C.F., Bianchi A., Deserra C., Migliori M:, Degli Angioli R., Marigliano V. RAPPORTO VALLE/PICCO E VARIABILITA'PRESSORIA DURANTE TERAPIA CON VALSARTAN Cattedra di Gerontologia e Geriatria, Istituto I° Clinica Medica, Universit? degli Studi "La Sapienza", Roma L'efficacia della terapia antiipertensiva ? determinata non solo dall'entit? dell'effetto ipotensivo ma anche dalla sua durata.E il controllo della variabilit? pressoria e della frequenza cardiaca, ulteriori fattori di rischio cardiovascolari, pu? migliorare la prognosi del paziente iperteso. Scopo dello studio ? stato valutare quindi la capacit? del Valsartan, antagonista dei recettori AT1 dell'angiotensina Il, non solo di ridurre la pressione arteriosa (PA), ma anche di garantire una buona uniformit? di azione durante l'intervallo di somministrazione e di diminuire la variabilit? pressoria e della frequenza cardiaca.A tal fine, sono stati studiati 15 soggetti con ipertensione lieve alla misurazione clinica secondo W.H.0 7 M e 8 F(et? media: 63.7 + 12.4), sottoposti a monitoraggio ambulatoriale della pressione arteriosa nelle 24 ore (ABPM), in condizioni ambientali e soggettive standardizzate, con apparecchio A&D TM 2421 2021, ad intervalli di misurazione di lO' nel periodo diurno (ore 7 23) e 15* nel periodo notturno (23 7), prima e durante trattamento con una dose singola giornaliera di 80 ing. di Valsartan. Criteri di esclusione: ipertensione secondaria, cardiopatie, obesit? (BMI > 30), neoplasie. Nei pazienti che hanno risposto alla terapia (responders) con una riduzione della PA di almeno il 10% (n"11), ? stato valutato il rapporto valle/picco (V/P) come indice di uniformit? dell'effetto ipotensivo nelle 24 ore della monosomministrazione farmacologica.Il rapporto V/P ? stato calcolato come rapporto tra valore medio di riduzione delle pressioni registrate nelle ultime due ore prima della successiva somministrazione (valle), e valore medio di riduzione delle pressioni registrate al picco dell'effetto antiipertensivo identificato ira la 4' e la & ora dell'assunzione del farmaco (picco).Il rapporto V/P ? stato considerato favorevole, in accordo a FDA, se > 0. 50, se cio? il farmaco al tempo di valle esercita un effetto antiipertensivo di almeno la met? di quello al tempo di picco.La variabilit? pressoria e della frequenza cardiaca ? stata espressa come deviazione standard (DS) della media dei valori rilevati nelle 24 ore I risultati sono mostrati nelle tabelle: Responders(n*11) Wash-out Valsartan 80 nig. P PAS 24 ore 147.9 16.1 132.4 ± 13.8 0.000 DS 18.8 5.8 18.1 ± 5.7 ns PAD 24 ore 86.5 8.9 7~"0 ± 5.3 0.000 DS 12.2 3.6 11,7 ± 2.1 ns FC 24 ore 75.3 8.5 75.8 10.1 ns DS 12.2 2.6 12.3 2.3 ns PAS = PA sistolica PAD = PA diastolica FC = frequenza cardiaca Rapporto valle/picco PAS PAD V/P medio 0.68 0.59 % responders con V/P > 0.5 90% 81 % Conclusioni: li Valsartan, bloccante i recettori AT, dell'angiotensina 11, riduce in misura significativa la PAS e la PAD e garantisce nella maggior parte dei pazienti una buona uniformit? dell'effetto ipotensivo, come evidenziato dal V/P favorevole nella quasi totalit? dei responders; scarsa ? invece la sua efficacia sulla variabilit? pressoria e della frequenza cardiaca che alcuni studi indicano come importanti fattori di rischio cardiovascolare. CICCONETTI P., FIONDA A., BAUCO C., MIGLIORI M., MARIGLIANO V. Deficit nutrizionale e demenza di Alzheimer: come individuarlo e prevenirlo. Riassunto. La perdita di peso ? un problema molto diffuso nei pazienti affetti da demenza di Alzheimer, che vivano in casa o che siano istituzionalizzati. Essa dipende da uno squilibrio tra quota energetica introdotta e quota energetica consumata. Se in una prima fase della malattia il calo ponderale pu? dipendere da fattori socio ambientali, psicologici e dalla riduzione dell'autonomia, negli stadi successivi esso ? la conseguenza di disturbi del comportamento alimentare (Adversive Feeding Behaviours: AFBs). Gli AFBs portano invariabilmente ad un deficit nutrizionale che, oltre che proteico lipidico, glicidico, ? anche vitaminico, e presenta una correlazione positiva con il livello di performance cognitiva, ripercuotendosi negativamente sul decorso della malattia. quindi importante effettuare una precoce identificazione degli AFBs (per mezzo della Scala di Blandford), specialmente di quelli suscettibili d'intervento. Inoltre, ? fondamentale cogliere tempestivamente l'esistenza del calo ponderale e di un eventuale stato di malnutrizione, servendosi di metodi d'indagine che ne permettano anche il successivo monitoraggio (Mini Nutritional Assessment: MNA). La terapia farmacologica del deficit cognitivo e del disturbo del comportamento alimentare, insieme a quella di eventuali stati concomitanti (depressione) ed a interventi di tipo nutrizionale, servir? ad evitare che s'instauri uno stato carenziale con ripercussioni negative sul decorso della malattia. RECENTI PROGRESSI IN MEDICINA; vol. 91, n3, pg 135-139, Marzo 2000. CICCONETTI P., CACCIAFESTA M., MONTEFORTE G., THAU F., DURANTE M., CHIAROTTI F., CIOTTI V., PICCIRILLO G.F., MARIGLIANO V. Event-related potentials in the elderly with new mild hypertension. Hypertension is a risk factor for cerebrovascular diseases (CVD) and cognitive impairment and the relative risk of CVD at every level of blood pressure (BP) is greater among the elderly. We submitted 20 elderly affected by new mild hypertension and 10 elderly normotensives to 24-hour ambulatory BP monitoring (ABPM), to evaluate their cognitive state using the Mini-Mental-State-Examination and to the recording of related acoustic evoked potentials (P300 and N2). We did not find significant differences for P300 latency between hypertensives and normotensives, while N2 latency recording showed a statistically significant protracted value in elderly hypertensives. In these patients we found a significant correlation between the N2 latency and systolic blood pressure values recorded by ABPM. These results demonstrated early functional alterations of cognitive state in elderly hypertensives, that are related to systolic blood pressure and future data might point to an earlier use of therapy CLIN. AND EXPER. HYPERTENSION; 22(6), pg 583-593, 2000. CICCONETTI P., CACCIAFESTA M., MIGLIORI M., DI GIOACCHINO C.F., VETTA F., CHIAROTTI F., MARIGLIANO V. 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. ARCH. GERONTOL. GERIATR.; vol.30, pg 225-236, 2000. ZANNINO G., GIANNI W., CICCONETTI P., MARIGLIANO V., CACCIAFESTA M. Aspetti molecolari delle malattie neurodegenerative. GERIATRIA; vol.12(4), pg 175-180, 2000. CICCONETTI P., FIONDA A., ZANNINO G., ETTORRE E., MARIGLIANO V. Riabilitazione nella demenza di Alzheimer. Alzheimer's disease is a neurodegenerative disease that causes a progressive decline of cognitive and behavioural functions. The simultaneous presence of these disorders requires a treatment not only for cognitive decline, but also for behavioural symptoms, depression and caregiver's stress. Research has made many efforts to develop a wide range of treatments, different from current pharmacological therapy, which is not resolutive, owing to the absence of an exact etiopathogenetic mechanism. Since new drugs have not been shown to be really effective in slowing cognitive impairment, various forms of rehabilitative interventions have been proposed in order to treat Alzheimer's disease. Their efficacy in the improvement of cognitive functions is still not completely clear. Surely, interesting results have been obtained from studies about Reality Orientation Therapy, Occupational Therapy and Memory Training. Music therapy might provide a new form of rehabilitative intervention, especially acting on the reducing of behavioural symptoms. These alternative forms of non pharmacological treatment may have a positive effect on caregiver. The heavy emotional burden of seeing a loved one becoming confused and isolated and of having to accept new responsibilities, may be reduced by rehabilitative supports, complementary to the pharmacological therapy. Caregiver stress could be reduced in two ways: by promoting the hope that something is being done for the patient and providing free time for himself. RECENTI PROGRESSI IN MEDICINA; vol.91, n.9, settembre 2000. CICCONETTI P., MARIGLIANO V. Ipertensione arteriosa nei molto anziani. Problemi di trattamento. Riassunto. Alcuni studi epidemiologici avevano evidenziato che, nei soggetti molto anziani ("very old", secondo la definizione anglo sassone), una bassa pressione arteriosa era associata con una maggiore mortalit? e l'ipertensione con una maggiore sopravvivenza. Ma successivi studi, anche della nostra Scuola, e i dati di Framingham hanno chiarito che la maggiore mortalit? nei "very old" con pi? bassa pressione arteriosa ? da attribuire a patologie preesistenti, delle quali la bassa pressione rappresenta una conseguenza pi? che la causa. Pur non essendo disponibili studi clinici controllati d'intervento specifici nei molto anziani, l'analisi dei risultati della terapia antiipertensiva nei sottogruppi di "very old" di alcuni trial sugli anziani ipertesi incoraggia il trattamento farmacologico anche in questa fascia di et? (> 80 anni), perlomeno per l'ipertensione sistolica isolata. La terapia dovr? fondarsi su una oculata scelta dei farmaci e andr? condotta con particolare cautela, al fine di prevenire disabilit?, senza peggiorare la qualit? della vita dei molto anziani. RECENTI PROGRESSI IN MEDICINA; vol. 92, n. 5, pg 345-349, maggio 2001. CICCONETTI P., DESERRA C., CIOTTI V., MARIGLIANO V. Ipertensione arteriosa, variabilit? pressoria e uricemia. The aim of our study was to evaluate serum levels of uric acid in stable hypertensive patients compared with non hypertensive patients of the same age, in order to verify the possible renal involvement and the role of 24 hour blood pressure variability which is now considered an important risk factor for end organ darnage. All patients were subrritted to measurement of serum levels of uric acid, to ambulatory blood pressure monitoring (ABPM), which is better related to organ damage and allows for a better evaluation of blood pressure variability. The results showed no white coat effect in hypertensive patients at the office measurement; they showed significantly higher 24 hour mean systolic and diastolic blood pressure values than in nornotensives. Serum levels of Uric acid resulted significantly higher in the hypertensive group than in the normotensives. For the blood pressure variability, there were not statistically significant differences between the two groups or correlation with serum levels of uric acid. Our study evidences, that the blood pressure variability does not seem to exercise an important influence on hypertensive renal organ damage. CARDIOL EXTRAOSP; vol. 1 , pg 48-50, 2001. CICCONETTI P., CACCIAFESTA M., MONTEFORTE G., CIOTTI V., MOIS? A., PICCIRILLO G., MARIGLIANO V. Studies on the brain event related potentials in the elderly with white-coat or isolated systolic hypertension. SUMMARY The aim of this study was to investigate brain organ damage or cerebrai alterations in eldery subjects with white coat systolic hypertension (WCH), isolated systolic hypertension (ISH) and normotensives (N), to verify the clinical significance of WCH, Thirty eldery untreated subjects were subdivided, after clinica] measurement of their arterial blood pressure values, according to the WHO Guidelines, and 24 hrs ambulatory blood pressure monitoring (ABPM) in three groups 10 N, 10 WCH and 10 ISH patients. All the patients were submitted to mini mental state examination (MMSE) and recording of event related potentials (ERP), determination of N2 (an index of early functional cognitive alterations) and P300 (an index of clinically evident cognitive deficit). We did not observe statistically significant differences among the three groups as regards the lag time of the P300 potential and MMSE scores. The lag time of the N2 wave showed a significant difference between the normotensives and ISH patients, but did not between the N or ISH and WCH groups. The lag time of N2 in WCH being intermediate between the other two groups, could be ascribed to higher blood pressure variability, and predicts future cognitive impairment ARCH GERONTOL GERIATR suppl. 7, pg 87-91, 2001. CICCONETTI P., CACCIAFESTA M, DESERRA C., FIDENTE D., LORIDO A., ETTORRE E., OTTAVIANI L., MARIGLIANO V. Changes of psychological state in elderly hypertensives with antihypertensive therapy. SUMMARY The aim of this investigation was to assess if the anxiety levels and the symptoms of depression in elderly subjects with hypertension might improve after antihypertensive therapy. Thirteen elderly subjects with mild systo diastolic hypertension received a Fosinopril treatment of 20 mg/day for 12 months. Before and after this treatment they underwent the following tests: state test anxiety inventory (STAI), geriatric depression scale (GIDS), and 24 hour ambulatory blood pressure monitoring (ABPM) to assess rea] pressure values. ABPM data reaffirmed the high values of blood pressure in the elderly hyper tensives identified by using clinical measurements and the fali in blood pressure after therapy. Our study did not reveal any significant difference in the anxiety levels after Fosinopril treatment, but the symptoms of depression significanfly improved (p < 0.01) after this therapy. This could lead to a reduction of the higher risk of stroke associated with depression in elderly hypertensives and even to a better quality of life. ARCH GERONTOL GERIATR suppl. 7, pg 93-97, 2001. TAFARO L., CICCONETTI P., MARTELLA S., TEDESCHI G., ZANNINO G., TROISI G., PASTENA I., FIORAVANTI M., MARIGLIANO V. An investigation on behavioral problems in centenarians. SUMMARY The characteristics of cognitive decline in extremely long living people are not well defined. Our study have assessed the cognitive function and the presence of behavioral disturbances in a group of 42 centenarians, in order to contribute to a better understanding of the needs of centenarians. The mini mental state examination (MMSE), Alzheimer disease assessment scale cognitive (ADAS Cog), and the empirical behavioral Alzheimer disease (Behave AD) rating scale were the measures applied to this sample composed of 9 males and 33 females with a mean age of 101.7 + 1.6 (± SD), range 101 108 years. According to the Behave AD scores, 42 % of these patients were classified as having no behavioral impairment, 30 % were considered with mild impairment, 21 % with a moderate impairment and 7 % with a severe impairment. The Behave AD score was significantly correlated with the measures of cognitive impairments indicating the multidimensional nature of this deterioration which is evident at a clinical level in a sizeable number of individuals aged more than 100 years. The most frequent behavioral disturbances in this sample ere generalized anxiety and depression, while thought and sensorial alterations are less frequent. ARCH GERONTOL GERIATR suppl. 7, pg 375-378, 2001. CICCONETTI P., TAFARO L., TEDESCHI G., TOMBOLILLO M.T., MARIGLIANO V. Fattori di rischio e patologie cardiovascolari nei centenari. Riassunto. La longevit? viene comunemente considerata il risultato dell'interazione tra fattori genetici, ambientali e psicosociali. I centenari, che hanno quasi raggiunto il limite massimo di vita (120 anni), sono esenti dalle patologie cardiovascolari o hanno una maggiore resistenza ad esse? Ed i fattori di rischio per esse, in che misura sono presenti? Abbiamo indagato la patologia cardiovascolare, ed i fattori di rischio ad essa correlati, in un gruppo di 148 centenari selezionati dai registri dell'anagrafe del Comune di Roma (et? media 101,8+1,9; range 100 108). Il loro stato di salute ? stato valutato tramite intervista diretta della durata di circa un'ora, condotta da un medico con formazione geriatrica presso il domicilio del paziente, che comprendeva anche la somministrazione di scale di valutazione geriatrica. La prevalenza della patologia cardiovascolare nei nostri centenari ? risultata del 16,7% ed ? rappresentata da scompenso cardiaco (8%), infarto miocardico (4,7%) e angina pectoris (4%). Tra i fattori di rischio cardiovascolare pi? frequenti risultano l'ipertensione arteriosa (31,1%) e l'ipercolesterolemia (21,7%), mentre ? assente il diabete. Questi dati, paragonati con quelli di fasce di et? meno avanzate, rilevano nei centenari una pi? bassa percentuale di patologia cardiaca nonché di fattori di rischio. Inoltre i centenari risultano aver segu?to regole di vita igieniche (dieta mediterranea, astensione dal fumo, esercizio fisico, basso grado di ansia e depressione) che hanno consentito la piena espressione del potenziale genetico a loro disposizione. Quindi, in conclusione, l'individuazione di mezzi specifici che ci consentano un intervento programmato per la prevenzione dei fattori di rischio e delle patologie cardiovascolari consentir? una maggiore diffusione del fenomeno longevit?, permettendo ad un numero sempre maggiore di soggetti di raggiungere il limite massimo della vita umana. RECENTI PROGRESSI IN MEDICINA vol. 92, n.12, pg 731-734, 2001. CICCONETTI P., CIOTTI V., TAFARO L., RIOLO N., MARIGLIANO V. Ipercolesterolemia, rischio cardiovascolare e terapia ipocolesterolemizzante nell'anziano. Riassunto. Il ruolo del colesterolo quale fattore di rischio cardiovascolare nell'et? avanzata ? attualmente controverso. Studi epidemiologici mostrano una correlazione continua tra colesterolemia e rischio cardiovascolare anche negli anziani, nei quali, pur verificandosi una riduzione del rischio relativo, si ha un maggior rischio assoluto e attribuibile. Nei soggetti di oltre 75 80 anni il colesterolo perde il ruolo di fattore di rischio, probabilmente per l'elevata comorbilit? tipica di quest'et?. 7? ial d'intervento dimostrano l'efficacia della terapia ipocolesterolemizzante con statine nella prevenzione secondaria anche negli anziani; minori evidenze si hanno nella prevenzione primaria. Gli orientamenti terapeutici suggeriscono un intervento farmacologico di prevenzione secondaria mirato sui livelli di colesterolo LDL (C LI)L), perché pi? correlato agli eventi cardiovascolari, nei giovani anziani (young elderly) e negli "anziani anziani" (old elderly). Nella prevenzione primaria sar? opportuno intervenire farmacologicamente fino ai 75 anni di et?, per raggiungere valori di C LI)L tanto pi? bassi quanto pi? numerosi sono i fattori di rischio; negli "old elderly" l'intervento terapeutico va valutato caso per caso in base all'et? del paziente e alle sue aspettative di vita. Le statine appaiono come i farmaci pi? efficaci e sicuri per raggiungere tale obiettivo. RECENTI PROGRESSI IN MEDICINA vol. 93, n.4, pg 264-272, 2002. MARIGLIANO V., TAFARO L, URSINO R, TROISI G, CICCONETTI P. Influenza dell'ambiente sull'invecchiamento LA MEDICINA ESTETICA 2002, anno 26, n 3, pg 302-308 MARTELLA S., CICCONETTI P., TAFARO L., ZANNINO G., TOMBESI F., CASAGRANDE RAFFI I. AND V MARIGLIANO Causes of death in over-85-year-old hospitalized patients: a retrospective study. Over the last decades the autopsy rate has been declining steadily and the autopsies are performed much less frequently in older people. The decline in the autopsy rate is associated with a reduced efficiency in measuring the accuracy of clinical diagnoses. The aim of this study was to analyze the autopsy rate, the causes of death and the clinical diagnostic accuracy in over85 year old patients. The study involved 1245 patients who died in University Polyclinic "Umberto 17' of Rome between January 1989 and December 1993. The low autopsy rate (15. 1 %) and percentage of agreement between clinical and pathological diagnoses we have found are comparable with those fbund in other studies and may be due to factors connected to the age. There is, in fact, a progressive tendency of the discrepancy rate to increase with age, probably because of the greater difficulty in making correct clinical diagnoses (lack of clear symptoms, multiple pathology). Our study has confirmed the importance of post mortem examination in diagnosing and determining the true causes of death in the elderly. Keywords: Autopsy rate, causes of death, clinical diagnoses, diagnostic accuracy, elderly. ARCHIVES OF GERONTOLOGY AND GERIATRICS 2002, suppl. 8 (in press). TAFARO L., CICCONETTI P., ZANNINO G., TEDESCHI G., TOMBOLILLO MT., TOMBESI F., ETTORRE E., MARIGLIANO V. Depression and aging: a survival study on centenarians. ARCHIVES OF GERONTOLOGY AND GERIATRICS 2002, suppl. 8 (in press). CICCONETTI P., TAFARO L., TEDESCHI G., TOMBOLILLO MT., CIOTTI V., TROISI G., MARIGLIANO V. Lifestyle and cardiovascular aging in centenarians. ARCHIVES OF GERONTOLOGY AND GERIATRICS 2002, suppl. 8 (in press). TAFARO L., CICCONETTI P., TEDESCHI G., TOMBOLILLO MT., MARIGLIANO V. Longevity and diabetes: a multidimensional assessment JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION 2002 vol 25 (in press) Efficacy of recombinant erythropoietin on the quality of life in patients over 60 years of age undergoing hemodialysis RUSSO GE, GIUSTI S, VITALIANO E, CARAMIELLO MS, MAURICI M, DE MARCO CM, PENNACCHIA M, D'AURIA F, BONELLO M, BRUNO C, MARIGLIANO V. We followed for a period of six months, 54 patients of over 60 years old, submitted to hemodialitic treatment. We gave human recombinant erythropoietin, average dosage 50 UI/Kg subcutaneously on alternative days, folic acid and iron supplements together with a proteic supply of 1.2 g/Kg/die (35 Kcal/Kg). The medullary response has been monitored with hematochemical tests; blood pressure and nutritional conditions have been evaluated. Furthermore, the patients were given a questionnaire to evaluate their quality of life. At the end of the follow up, 50 patients responded positively to therapy. These patients showed an increase of RBC (from 2,789,780 +/- 259,310 to 3,313,110 +/- 472,780 p < 0.001) of HCT (from 21.86% +/- 2.16% to 27.18 +/- 2.74% p < 0.0001) and of Hb (from 7.72 +/- 1.12 g/dl to 9.28 +/- 0.98 g/dl p < 0.006). Total protein and albumin increased too. Furthermore they showed a progressive increase of "performance status". Our results confirm efficacy of erythropoietin in the treatment of anemia in elderly hemodialized patients. Clin Ter 1997 Mar;148(3):89-93 Plasmapheresis and mushroom poisoning:report of a case of Amanita phalloides poisoning RUSSO GE, GIUSTI S, MAURICI M, BOSCO M, VITALIANO E, CARAMIELLO MS, BAUCO B, DE MARCO CM, MARIGLIANO V. A case of amanita phalloides which presented a typical picture of phalloides intossication has been treated at our Centre. The patient was submitted to four treatments of plasmaexchange (Plasmafiltration), exchanging from 70 to 80% of the plasmatic volume and using substitutive liquids 4% albumine and frozen plasma, using as filter Plasmaflo Asahi OP-O5 (1) and Plasmapheresis equipment SIFRA mod. 914. Already after the first treatment there was an improvement of the general condition with a stabilization of the renal and hepatic parameters at the end of the cycle. Clin Ter 1997 May-Jun;148(5-6):277-80 Comparative study of the modification of arterial pressure in adult and aged subjects treated with hemofiltration. Preliminary results RUSSO GE, GIUSTI S, VITALIANO E, MAURICI M, DE MARCO CM, CARAMIELLO MS, BONELLO M, PENNACCHIA M, BRUNO C, SCUTERI A, MARIGLIANO V. Haemodynamics modifications in 49 patients divided in two groups consisting of 21 young people (average age 43 +/- 12 yrs.) and 28 elderly people (average age 72 +/- 7 yrs.) who have undergone at least three treatments with haemofiltration for congestive cardiac decompensation and chronic renal failure have been evaluated. Systolic and diastolic blood pressure and heart rate have been monitored for each patient in a length of time of iT, T30 min., T60 min., fT. The results show a statistically significant reduction of the systolic pressure during the time interval iT-T30 min. in subjects over 65, contrary to the control group. Such preliminary results can be justified by the haemodynamic modifications correlated to the elderly process. In any case the hypothesis cited by the authors need further testing even if confirming the indication of the dialytic treatment on patients over 65 through haemofiltration techniques. Clin Ter 1997 May-Jun;148(5-6):225-8 Efficacy of recombinant erythropoietin on the quality of life in patients over 60 years of age undergoing hemodialysis RUSSO GE, GIUSTI S, VITALIANO E, CARAMIELLO MS, MAURICI M, DE MARCO CM, PENNACCHIA M, D'AURIA F, BONELLO M, BRUNO C, MARIGLIANO V. We followed for a period of six months, 54 patients of over 60 years old, submitted to hemodialitic treatment. We gave human recombinant erythropoietin, average dosage 50 UI/Kg subcutaneously on alternative days, folic acid and iron supplements together with a proteic supply of 1.2 g/Kg/die (35 Kcal/Kg). The medullary response has been monitored with hematochemical tests; blood pressure and nutritional conditions have been evaluated. Furthermore, the patients were given a questionnaire to evaluate their quality of life. At the end of the follow up, 50 patients responded positively to therapy. These patients showed an increase of RBC (from 2,789,780 +/- 259,310 to 3,313,110 +/- 472,780 p < 0.001) of HCT (from 21.86% +/- 2.16% to 27.18 +/- 2.74% p < 0.0001) and of Hb (from 7.72 +/- 1.12 g/dl to 9.28 +/- 0.98 g/dl p < 0.006). Total protein and albumin increased too. Furthermore they showed a progressive increase of "performance status". Our results confirm efficacy of erythropoietin in the treatment of anemia in elderly hemodialized patients. Clin Ter 1997 Mar;148(3):89-93 Terapia antiipertensiva con calcio-antagonisti e ACE-inibitori: utilit? del monitoraggio dinamico 24 ore della pressione arteriosa. VILLATICO CAMPBELL S., DI MAIO F., PANNARALE G., CARMENINI G., MELONI F., GUELI N., RIZZO V., CICCONETTI P., MARIGLIANO V. Atti XII Congresso Nazionale della Societ? Italiana dell'Ipertensione Arteriosa, 261, 1995, Napoli. Carotid-artery disease and cognitive deficit in the elderly patients. MELONI F., DE GENNARO E., IDONE G., GALEANO D., GUELI N., MARIGLIANO V. Atti International Symposium Psychoneuroendocrine and Immunological Correlates of Aging, Pavia, settembre 1997. Trattamento palliativo della carcinomatosi peritoneale da carcinoma ovarico avanzato in pazienti anziane: ruolo dell'Interferon -2D ricombinante. GIANNI W., BIANCO V., TRANI I., PIETROPAOLO M., TROISI G., FOLCANDO E., CACCIAFESTA M., GUELI N., MARCHEI P., MARIGLIANO V. Atti II Congresso Nazionale sui Tumori in Et? Geriatrica, 147, Roma, 1997. Versamenti pleurici neoplastici nell'anziano: utilit? dell'infusione di Interferon Beta ricombinante. GIANNI W., PIETROPAOLO M., BIANCO V., ROZZI A., GUELI N., MARCHEI P., MARIGLIANO V. Atti Congresso Societ? Italiana Geriatri Ospedalieri, 96, Reggio Emilia, 1998. Gemcitabine in aged NSCLC patients: preliminary results. BIANCO V., GIANNI W., PIETROPAOLO M., CAMPISI C., ZANONI M., GUELI N., MARIGLIANO V., MARCHEI P. Annals of Oncology, 9, suppl 3, 67, Kluwer Academic Publishers, 1998. 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 An investigation on behavioral problems in centenarians. TAFARO L, CICCONETTI P, MARTELLA S, TEDESCHI G, ZANNINO G, TROISI G, PASTENA I, FIORAVANTI M, MARIGLIANO V. Arch Gerontol Geriatr 2001 Jan;33 Suppl 1:375- Role of 99mTc-Sestamibi scintimammography by SPEM camera in the management of breast cancer in the elderly. DE VINCENTIS G, GIANNI W, PANI R, CACCIAFESTA M, PELLEGRINI R, SOLURI A, TROISI G, MARIGLIANO V, SCOPINARO F. The incidence of breast cancer in the elderly is 10 fold higher than in the population younger than 65 years. Moreover, in this segment of the population there are not defined clear practice guidelines regarding patient management. X-ray mammography, the most widely used diagnostic technique, is often inadequate to differentiate benign from malignant lesions. 99mTc Sestamibi scintimammography plays an important role as complement to mammography; in fact it is a very sensitive and specific method for breast cancer detection, when cancers > 1 cm diameter are considered. However, sensitivity values fall to 50-60% in the case of small tumors (T1a and T1b). In this study we present the results of a new Small Field Of View (SFOV) Gamma Camera with very high spatial resolution that allows the first Single Photon Emission Mammography (SPEM). Eighteen patients aged 71 +/- 6 years with mammographically detected breast lesions were submitted to a Prone Scinti Mammography (PSM) by conventional Gamma Camera and to a SPEM on craniocaudal view. A final diagnosis was reached by histopathology. SPEM correctly diagnosed 15 of 16 cancers, while PSM was not able to recognize 5 malignant lesions with subcentimeter size. Both the techniques provided normal findings in the case of benign lesions. The 99mTc Sestamibi scintimammography, particularly when performed by SPEM camera, is a sensitive, specific, and non invasive method to define the nature of radiologically described breast masses and would be very useful as a complement to X-ray mammography in screening programs for breast cancer. Breast Cancer Res Treat 1998 Mar;48(2):159-63PMID: 9596487 Neuro-vegetative regulation of the cardiovascular system. Role of the functional independence of the right and left hemisections BALSANO F, MARIGLIANO V, LEGGIO F, MUSCA A, CORDOVA C, TROISI G. G Ital Cardiol 1978 Jun;8(6):670-82 Experimental study of the different actions of right and left neurovegetative hemisections on the cardiovascular system. Demonstration of 2 types of reflexes, common and specialized. Stimulation of the right and left pericarotid plexus in subjects with atrioventricular block of grade II, type II MARIGLIANO V, CACCIAFESTA M, TROISI G, MUSCA A, CORDOVA C. Boll Soc Ital Cardiol 1978;23(11):1911-4 The importance of vagal hemisectorial stimulation in the distinction between nodal and left atrial ectopic rhythms MARIGLIANO V, DE MARZIO P, CACCIAFESTA M, TROISI G, MUSCA A, CORDOVA C. Boll Soc Ital Cardiol 1978;23(11):1897-909 The concept of normality and electrocardiographic problems in the age MARIGLIANO V, ALESSANDRI C, SCHMIDT MC, CACCIAFESTA M, TROISI G, GIORDANO M. Boll Soc Ital Cardiol 1978;23(11):1877-95 Electrocardiographic problems of the tenth decade of life MARIGLIANO V, SCHMIDT MC, ALESSANDRI C, TAGLIACCICA G, CACCIAFESTA M, TROISI G. Boll Soc Ital Cardiol 1978;23(11):1869-76 Atrial fibrillation in the aged and the problem of normality in medicine MARIGLIANO V, CACCIAFESTA M, TROISI G, MEZZA A, TOMASSINI M, GIORDANO M. Boll Soc Ital Cardiol 1978;23(11):1841-67 Experimental studies on the different action of right and left neurovegetative hemisections on the cardiovascular system. Demonstration of 2 types of reflexes, common and specialized. Stimulation of the right and left pericarotid plexus in subjects with left branch block MARIGLIANO V, MUSCA A, CORDOVA C, TROISI G, TAGLIACCICA G. Boll Soc Ital Cardiol 1978;23(5):909-12] Experimental studies on the different action of right and left neurovegetative hemisections on the cardiovascular system. Demonstration of 2 types of reflexes, common and specialized. Stimulation of the right and left pericarotid plexus in subjects with grade II atrioventricular block MARIGLIANO V, MUSCA A, CORDOVA C, TROISI G, TAGLIACCICA G. Boll Soc Ital Cardiol 1978;23(5):901-4 Experimental studies on the different action of right and left neurovegetative hemisections on the cardiovascular system. Demonstration of 2 types of reflexes, common and specialized. Stimulation of the right and left pericarotid plexus in subjects with atrial fibrillation MARIGLIANO V, MUSCA A, CORDOVA C, TROISI G, TAGLIACCICA G. Boll Soc Ital Cardiol 1978;23(5):893-6 Experimental studies on the different action of right and left neurovegetative hemisections on the cardiovascular system. Demonstration of 2 types of reflexes, common and specialized. Stimulation of the right and left pericarotid plexus in subjects with atrial flutter MARIGLIANO V, MUSCA A, CORDOVA C, TROISI G, CAMMARELLA I. Boll Soc Ital Cardiol 1978;23(5):889-92 Danno aorto-carotideo nell?anziano e profilo delle Apolipoproteine E. E.Bucci, R. Antonini, A. Vitarelli, M. Gnecchi, T. Peppe, R.M. Scoyni, I. Trani, V. Giuliano, V. Marigliano. Atti. 4th International Congress on Hypertension in the elderly-Rome, november 1999. Elderly Hypertension and aortic damage. X-ray detectable calcification versus TEE score. Initial report. M. Gnecchi, A. Vitarelli, T. Peppe, P. Raganato, R.M. Scoyni,I.Trani, A. Hekmatoudtabrizi, V. Marigliano. Atherosclerosis 151 (suppl. 1): s 108, july 2000. Stato cognitivo nell?anziano coronaropatico: associazione con il fenotipo delle apolipoproteine E. G.Zannino, M. Gnecchi, M.G. Marotta, A. Bucci, A.G. Scarno, G. Benedetti, S. Musar?, R. Antonini, V. Marigliano. Geriatria vol. XIII (suppl. 1), gennaio-febbraio 2001. Site and extension of extracoronary atherosclerosis in coronary patients. Association with apoliprotein E profile. Bucci, M. Gnecchi, Iacoboni C., R. Antonini, G. Zannino, S.Musar?, V. Giuliano, L.Lalloni, V. Marigliano. Atherosclerosis vol 2 n°22: 70- P 97, may 2001.