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Introduction: Altered profile of RR variability and reduced baroreflex gain, as autonomic proxies, are observed in hypertensive individuals., Aim: To assess whether using logistic models and cross-validation techniques autonomic proxies can be used to identify clinical hypertensive and normotensive groups., Methods: An observational study on 405 individuals (155 mild hypertensive and 250 controls). We used four steps for statistical analysis: preliminary descriptive statistics; logistic regression modelling; detection of best parsimonious set of variables; and concordance analysis between clinical and autonomic hypertension profile., Results: Accuracy index (rate of correct identifications of normotensive and hypertensive states), computed on each of the four gradually more complex logistic models (from A to D), reached its highest value (82.7%), in the most complete model D, including autonomic nervous system indices (RR variability and baroreflex gain), age and sex. Measures of predictive performance increased from the simplest model to the most complex one [model D, positive predictive value (PPV) = 0.767, negative predictive value (NPV) = 0.866], with higher specificity than sensitivity. A parsimonious set of autonomic proxies (Mean RR, ΔRRLFnu - i.e. change from rest to standing up - baroreflex gain combined with age and sex) led to an accuracy index of 80.5%, thus proving to have discriminant and predictive powers in detecting hypertension very similar to the whole set of the explicative variables comprised in the complete model D., Conclusion: The clinical value of the observation that the information collectively carried by a small subset of indirect autonomic proxies may identify either hypertensive or normotensive groups needs to be further investigated.

Objective: Aim of the study was to assess the role of family history, physical activity and parental smoking in the prediction of BMI, SBP and hypertension risk in children., Participants and Methods: In a paediatric primary care setting, a sample of 1310 children aged 5-14 years was systematically selected by 48 family paediatricians in northern Italy. BMI, waist circumference-to-height ratio (WtHr), SBP and DBP were measured and the information on the presence of small birth weight for gestational age (SGA) and early adiposity rebound (EAR) was collected. Data concerning exercise, video time, family history for cardiovascular diseases and parental smoking were derived from parental interview. Data were collected using an 'ad hoc designed' electronic sheet available online., Results: Multiple linear regression showed that the presence of EAR, low exercise (<2 h/week), high video time (>2  h/day TV/videogames/computer) and parental smoking were associated to higher BMI (z-score; P < 0.005). Age, BMI (z-score), WtHr, presence of SGA, low exercise, high video time and family history of cardiovascular diseases were associated to SBP values (P < 0.03). Logistic regression analysis showed that factors related to risk of hypertension and prehypertension were BMI (z-score; odds ratio, OR 2.63; 95% confidence interval, CI 2.12-3.28), WtHr (OR 1.13; 95% CI 1.10-3.28) and low exercise (OR 1.58; 95% CI 1.12-2.24; P <0.01)., Conclusion: Our study demonstrates that a simple tool like a cardiovascular multi-item sheet can provide useful information to paediatricians for child health. Physical exercise plays a pivotal role in obesity prevention and protection from hypertension risk.

Objectives: This study addressed the relationship between spontaneous baroreflex sensitivity and carotid mechanical properties in a clinical setting., Methods: In 191 normal volunteers (age range 20-60 years, mean 44 ± 13), spontaneous indices of baroreflex regulation were obtained noninvasively in the time (baroreflex slope, BRS) and frequency domains (α index and systolic arterial pressure-RR interval transfer gain) as well as using an exogenous autoregressive causal model (A.XAR); carotid mechanical properties were estimated by ultrasound. The link between mechanical measures and spontaneous baroreflex indices was explored by multivariate analysis and linear modeling., Results: Participants were divided into five groups according to age decades. With advancing age we observed a decrease in spontaneous baroreflex indices (BRS from 31.2 to 16.3; α index from 27.4 to 13.6; RR-SAP gain at high frequency from 31 ± 3.0 to 14 ± 3.0 ms/mmHg all P < 0.001) and increase in carotid intima-media thickness (IMT: from 0.53 to 0.69 mm; P < 0.001) and stiffness (local wave speed: from 4.0 to 6.9 m/s; both P < 0.001). A significant correlation was found between spontaneous indices of baroreflex sensitivity and carotid mechanical properties, particularly wave speed (r = -0.328, P < 0.001). After adjusting for age and sex, a significant correlation remained between RR-SAP gain and wave speed and between A.XAR and IMT. Factor analysis and automatic linear modeling confirmed the observation that mechanical carotid properties are strong predictors of the age-related reduction of spontaneous baroreflex., Conclusion: A significant correlation between spontaneous baroreflex indices and local carotid mechanical properties supports the idea that they should be considered in the physiology of baroreflex regulation.

Background: Recent epidemiological data indicate that chronic stress is an important component of cardiovascular risk, implicitly suggesting that stress management might offer a useful complement to orthodox medical treatment and prevention of hypertension. In this context, information on mechanisms, such as subclinical increases in arterial pressure and sympathetic drive, is well documented. Conversely, evidence on methodologies and comparative efficacy needs to be improved. Accordingly, this study was planned to test the autonomic and subjective effects of two popular modalities of stress management., Methods: We studied 70 patients complaining of stress-related symptoms, avoiding any potential autonomic confounder, such as established hypertension or drug treatment. Patients were divided in three groups: group I (n = 30) followed a breathing-guided relaxation training (active); group II (n = 15) an oriental massage, shiatsu (passive); and group III (n = 25) followed a sham intervention. Subjective effects of stress were assessed by validated questionnaires and autonomic nervous system regulation by spectral analysis of RR interval variability. Factor analysis was used to extract information simultaneously embedded in subjective and functional data., Results: Although the problem of a greater quantity of treatment procedure in the active group than in the passive group existed, results showed that active relaxation, further to slightly reducing arterial pressure, might be more effective in relieving symptoms of stress and inducing an improved profile of autonomic cardiovascular regulation, as compared with passive massage or sham intervention., Conclusion: This active technique seems capable of beneficially addressing simultaneously the individual psychological and physiopathological dimensions of stress in clinical settings, with potentially beneficial effects on cardiovascular risk profile.

Objectives: We hypothesized that addressing the 24-h relationship between RR interval and systolic arterial pressure (SAP) during ambulatory blood pressure monitoring could detect alterations in circadian arterial pressure and heart rate profile and could also be linked to the ambulatory arterial stiffness index., Methods: We analyzed retrospectively 676 ambulatory blood pressure monitoring 24-h recordings. Individuals were median split into low (n = 338) and high (n = 338) SAP groups (mean 24 h of 120 +/- 7, 140 +/- 10 mmHg, respectively). We estimated for each individual ambulatory blood pressure monitoring, the slope (ms/mmHg) of the regression of RR interval on SAP over 24-h (defined as theta index)., Results: Theta index was significantly (P < 0.001) steeper in individuals with lower pressure than those with higher pressure, whereas day-night difference in SAP did not differ significantly. Theta index was also less negative in nondipper than in dipper individuals and displayed a significant interaction (P < 0.001) with hypertension. The theta index correlated significantly with age and ambulatory arterial stiffness index. Moreover, approximately 14-month reproducibility, as assessed by intraclass correlation coefficient, for theta index was similar to SAP (0.703 and 0.757, respectively)., Conclusion: These results indicate that theta can detect differences in circadian arterial pressure profile that could assess the efficiency of arterial pressure (and heart rate) regulatory mechanisms over the whole day in individuals with different arterial pressure levels. Theta can be easily obtained under ambulatory conditions without any assumption on underlying mathematical models or operator-dependent attribution of arterial pressure and heart rate values to daytime or night-time subperiods. Cross-sectional and prospective studies relating theta to target organ damage and cardiovascular outcomes will inform us about its clinical relevance.

Background: Physical inactivity represents a major risk for cardiovascular disorders, such as hypertension, myocardial infarction or sudden death; however, underlying mechanisms are not clearly elucidated. Clinical and epidemiological investigations suggest, beyond molecular changes, the possibility of an induced impairment in autonomic cardiovascular regulation. However, this hypothesis has not been tested directly., Methods: Accordingly, we planned a study with noninvasive, minimally intrusive, techniques on healthy volunteers. Participants were maintained for 90 days strictly in bed, 24 h a day, in head-down (-6 degrees ) position (HDBR). Physical activity was thus virtually abolished for the entire period of HDBR. We examined efferent muscle sympathetic nerve activity, as a measure of vascular sympathetic control, baroreceptor reflex sensitivity, heart rate variability (assessing cardiovagal regulation), RR and systolic arterial pressure and low-frequency and high-frequency normalized components (as a window on central oscillatory regulation). Measures were obtained at rest and during simple maneuvers (moderate handgrip, lower body negative pressure and active standing) to assess potential changes in autonomic cardiovascular responsiveness to standard stimuli and the related oscillatory profiles., Results: HDBR transiently reduced muscle sympathetic nerve activity, RR, heart rate variability and baroreceptor reflex sensitivity late during HDBR or early during the recovery phase. Conversely, oscillatory profiles of RR and systolic arterial pressure variability were maintained throughout. Responsiveness to test stimuli was also largely maintained., Conclusion: Prolonged inactivity as induced by HDBR in healthy volunteers reduces both cardiovagal and vascular sympathetic regulation, while largely maintaining peripheral responsiveness to standardized stimuli and sparing the functional structure of central oscillatory cardiovascular regulation.

Objective: To assess the relationship between insulin resistance and baroreflex gain (BRS) in the context of the metabolic syndrome., Design: Observational population study., Patients: We studied the healthy population of a small Mediterranean island (Linosa, about 0.5 square miles, 450 inhabitants) where genetic, psychosocial and behavioral bias is likely to be minimal for historical and social reasons., Measures: Baroreflex gain (BRS, by the frequency domain alpha index) and indices of autonomic regulation of the sino-atrial (SA) node derived from spectral analysis of RR interval variability were obtained, together with metabolic and behavioral indicators in the 144 participating subjects (age range 20-82 years). Carotid artery thickness (CCA) was also obtained with computer-aided ultrasound techniques. Insulin resistance was estimated by the homeostasis model assessment (HOMA), and subjects divided in tertiles accordingly., Results: BRS appeared to be reduced progressively with increasing levels of HOMA (respectively, 21.0 +/- 2.6, 17.7 +/- 1.7, 15.7 +/- 1.9 ms/mmHg, P < 0.03), while spectral indices of autonomic SA regulation appeared to be only insignificantly affected. Conversely, CCA was significantly increased with increasing HOMA (P < 0.024). Furthermore, BRS appeared to be significantly correlated with various elements of the metabolic syndrome, with CCA and abdominal obesity showing the strongest link., Conclusions: In an otherwise healthy population, BRS, but not spectrally derived indices of SA node autonomic regulation, are progressively reduced with increasing severity of insulin resistance, possibly as a consequence of attendant carotid artery thickening.

Background: Chronic orthostatic intolerance (COI) is a common and disabling autonomic syndrome of unclear pathophysiology. We tested the hypothesis that baroreflex and autonomic responses to graded lower body suction (LBNP, up to -40 mmHg) could be altered in COI patients., Methods: Electrocardiogram (ECG), non-invasive arterial blood pressure and respiratory activity were measured during progressive LBNP (seven patients and seven volunteers). Lumped arterial baroreflex sensitivity (alpha index), and its arterial and cardiopulmonary components, were assessed by multivariate closed-loop analysis of RR interval and systolic arterial pressure (SAP) spontaneous variabilities and respiration. Monovariate spectral analysis of RR interval and SAP variability provided markers of autonomic regulation of the sinoatrial (SA) node and of vascular sympathetic modulation., Results: Similar reductions in overall and cardiopulmonary baroreflex gain were observed in both groups in response to graded LBNP. In contrast, only controls demonstrated a selective increase in arterial baroreflex sensitivity, at low-grade LBNP. Clear increases in the low-frequency component of RR interval variability (LFRR) [and decreases in the high-frequency component of RR interval variability (HFRR), both in normalized units] were observed in controls with graded LBNP, while insignificant changes occurred in COI patients, who showed, conversely, exaggerated sympathetic vasomotor responses [as assessed by the low frequency component of SAP variability (LFSAP)]., Conclusions: Patients with chronic orthostatic intolerance show distinct signs of altered baroreflex and autonomic regulation of the SA node and of the vasculature in response to graded LBNP.

Objective: The aim of our study was to assess the effects of acute and chronic smoking on skin microvascular properties of young healthy subjects., Design: An observational study, using a totally non-invasive approach, employing continuous palmar microvascular flow (laser Doppler) and arterial pressure measurements, to compute estimates of microvascular resistive (Z0) and oscillatory (impedance, i.e. ZC) properties. Measures were obtained at baseline and after iontophoretic administration of acetylcholine (ACh), an endothelium-dependent vasodilator and of sodium nitroprusside (NP), an endothelium-independent vasodilator., Participants: A total of 20 healthy male subjects (nine habitual smokers and 11 non-smokers; aged 27 +/- 1 and 29 +/- 2 years, respectively) in resting conditions and during administration of ACh and of NP (in two different days), before and after smoking one cigarette were evaluated., Results: Smokers showed significant lower baseline Z0 and ZC than non-smokers. In non-smokers, ACh and NP iontophoresis induced a significant decrease of both Z0 and ZC, before and after smoking one cigarette (P < 0.02). Conversely, in smokers, both Z0 and ZC were not affected by ACh iontophoresis before acute smoking, while, after smoking, a significant decrease of both Z0 and ZC (P < 0.02) was detected after ACh challenge. In smokers, both Z0 and ZC were not affected by NP iontophoresis, either before or after smoking a cigarette., Conclusions: Smokers appeared characterized by a complex disruption of peripheral microcirculatory regulation, including inappropriate resting vasodilation, impaired endothelium-dependent and independent vasodilation, paradoxical recovery of endothelium-dependent vasodilation in response to acute smoking.

Objectives: Spectral analysis of heart rate variability (HRV) provides potentially useful information on autonomic disturbances of human hypertension. However, its practical use outside the clinical laboratory is largely unexplored. The aim of this study was to test the feasibility of assessing HRV from the general practitioner's (GP's) office, using a novel transtelephonic approach., Design: Parallel study on two similar groups: 150 subjects (100 hypertensives and 50 normotensives) studied in our hospital clinic and compared with 150 subjects studied in an out-of-hospital practice (100 hypertensive subjects from GPs' surgeries and 50 normotensive subjects participating in a multinational company's health maintenance programme)., Methods: Spectral analysis of RR interval variability was used to assess autonomic regulation of the sino-atrial (SA) node, both at rest and during standing. For the out-of-hospital practice, strings of continuous electrocardiograms (ECGs), recorded with a microminiature instrument, were fed, off line, through standard telephone lines to our laboratory for subsequent spectral analysis., Results: RR spectral profiles obtained from healthy controls or hypertensive patients examined in their GPs' surgeries were similar to those obtained in a hospital clinic, both at rest and when standing up., Conclusions: The present study shows the feasibility of using a transtelephonic approach to perform spectral analysis of heart rate variability from physicians' surgeries. This method could favour a more widespread use of autonomic assessment in the clinical management of hypertension.

Objective: To examine the relationship between heart rate variability (HRV) and baroreflex sensitivity (BRS)., Design: An observational study, with no intervention, in 55 volunteers with a wide range of arterial pressure (60-90/115-185 mmHg)., Methods: Volunteers were studied first in the laboratory, with continuous measurement of systolic arterial pressure and electrocardiogram to obtain a frequency domain measure of baroreflex sensitivity (index alpha). Immediately afterwards, while the individual was ambulant, a Holter recording was obtained in order to compute time domain [standard deviation of consecutive normal R-R intervals (SDNN) and the percentage of successive R-R differences > 50 ms (PNN50)], and frequency domain measures of HRV. Linear correlation was used to test the statistical link between index alpha and HRV indices., Results: Significant correlations were observed between index alpha and SDNN (r = 0.30; P < 0.02) and PNN50 (r = 0.48; P < 0.001), and between index alpha and total power (r = 0.53; P < 0.001), and absolute powers of the 0.0001-0.04 Hz components of R-R interval variability in 24 h (r = 0.47; P < 0.001)., Conclusion: The major findings of this study are the clear demonstration of a significant correlation between a laboratory measure of baroreflex sensitivity and 24 h measures of HRV, obtained immediately afterwards. Notably, this correlation was found with both time domain and absolute, but not normalized, spectral measures of R-R interval variability. In addition, different levels of individual activity, as assessed by separate examination of daytime and night-time periods, did not seem to influence this relationship.