Fixed and autoadjusting continuous positive airway pressure treatments are not similar in reducing cardiovascular risk factors in patients with obstructive sleep apnea.

BACKGROUND: A strong association between obstructive sleep apnea (OSA) and the risk for cardiovascular and cerebrovascular diseases has been reported. Continuous positive airway pressure (CPAP) is the first-line therapy for OSA, able not only to reduce daytime sleepiness but also to improve cardiovascular and metabolic outcomes. Autoadjusting CPAP (APAP), an alternative treatment to CPAP, can reduce OSA symptoms while increasing long-term CPAP compliance without the high costs of CPAP titration. However, no data are available on the effects of APAP on cardiovascular risk factors METHODS: We performed standard full polysomnography; obtained plasma levels of glucose, insulin, and C-reactive protein (CRP); and measured systolic BP (SBP) and diastolic BP (DBP) in 31 patients with newly diagnosed, severe OSA. After standard CPAP titration, all subjects were randomized to CPAP or APAP treatment. Measurements were obtained at baseline and after 3 months of treatment. RESULTS: The two groups were similar in terms of age, sex, body mass index (BMI), and severity of OSA. SBP, DBP, heart rate (HR), homeostasis model assessment index (HOMA-IR), and CRP were similar in the two groups. After 3 months of treatment, BMI, HR, and compliance to therapy were also comparable. OSA indexes were significantly reduced in both groups. Significant reductions in SBP, DBP, and HOMA-IR were observed in the CPAP group but not in the APAP group, while CRP plasma levels were similarly reduced. CONCLUSIONS: Our results suggest that CPAP and APAP, despite significant effects on OSA indexes and symptoms, do not improve cardiovascular risk factors in the same fashion.

Complexity and nonlinearity in short-term heart period variability: comparison of methods based on local nonlinear prediction.

This paper evaluates the paradigm that proposes to quantify short-term complexity and detect nonlinear dynamics by exploiting local nonlinear prediction. Local nonlinear prediction methods are classified according to how they judge similarity among patterns of L samples (i.e., according to different definitions of the cells utilized to discretize the phase space) and examined in connection with different types of surrogate data: 1) phase-randomized or Fourier transform based, FT; 2) amplitude-adjusted FT, AAFT; 3) iteratively-refined AAFT, IAAFT, preserving distribution IAAFT-1; 4) IAAFT preserving power spectrum, IAAFT-2. The methods were applied on ad-hoc simulations and on a large database of short heart period variability series (approximately 300 cardiac beats) recorded in healthy young subjects during experimental conditions inducing a sympathetic activation (head-up tilt, infusion of nitroprusside, or handgrip), a parasympathetic activation (low dose administration of atropine or infusion of phenylephrine), a complete parasympathetic blockade (high dose administration of atropine), or during controlled respiration at different breathing rates. As to complexity analysis we found that: 1) although complexity indexes derived from different methods were different in terms of absolute values, changes due to experimental conditions were consistently detected; 2) complexity was significantly decreased by all the experimental conditions provoking a sympathetic activation and by controlled respiration at slow breathing rates. As to detection of nonlinearities we found that: 1) IAAFT-1 and IAAFT-2 surrogates performed similarly in all protocols; 2) FT and IAAFT surrogates detected about the same percentage of nonlinear dynamics in all protocols; 3) AAFT surrogates were inappropriate with all the methods and should be dismissed in future applications; 4) methods based on overlapping cells with variable size were characterized by a larger rate of false detections of nonlinear dynamics; 5) short-term heart period variability at rest was mostly linear; 6) controlled respiration at slow breathing rates increased nonlinear components, while the separate activation of the two branches of the autonomic nervous system (i.e., sympathetic or parasympathetic) was ineffective at this regard.

Early abnormalities of vascular and cardiac autonomic control in Parkinson's disease without orthostatic hypotension.

Cardiac autonomic abnormalities have been described in Parkinson's disease. Little is known about possible alterations of vascular sympathetic regulatory activity in patients without orthostatic hypotension or symptoms of orthostatic intolerance. Nineteen patients with Parkinson's disease without orthostatic hypotension (PD), 21 with orthostatic hypotension (PDOH), and 20 healthy controls underwent ECG, beat-to-beat arterial pressure, and respiration recordings while recumbent and during a 75 degrees head-up tilt. Spectrum analysis of RR interval and systolic arterial pressure (SAP) variability provided indices of cardiac sympathovagal interaction (low frequency [LF]/high frequency [HF]) to the sinoatrial node and sympathetic vasomotor control (LF(SAP)). Arterial baroreceptor mechanisms were assessed by the spontaneous sequences technique and bivariate spectrum analysis (alpha index). Plasma catecholamines provided the neurohormonal profile. At rest, hemodynamics and spectral markers of autonomic function were similar in PD and control subjects. Norepinephrine was lower in PD and PDOH than in control subjects. In PDOH, SAP was higher, whereas LF/HF ratio and LF(SAP) were lower compared with control subjects. During tilt, SAP was unchanged in PD; however, similar to PDOH, the increase of heart rate, LF/HF ratio, and LF(SAP) was blunted compared with control subjects. Baroreflex indices were unmodified in PD and PDOH compared with control subjects. Initial alterations in both cardiac and vascular sympathetic modulatory activity were found in PD and revealed by a gravitational stimulus. Prompt recognition of sympathetic abnormalities might result in earlier therapeutic intervention, reduced orthostatic intolerance, and increased quality of life.

Role of the autonomic nervous system in generating non-linear dynamics in short-term heart period variability.

We evaluated the role played by the autonomic nervous system in producing non-linear dynamics in short heart period variability (HPV) series recorded in healthy young humans. Non-linear dynamics are detected using an index of predictability based on a local non-linear predictor and a surrogate data approach. Different types of surrogates are utilized: (i) phase-randomized Fourier-transform based (FT) data; (ii) amplitude-adjusted FT (AAFT) data; and (iii) iteratively refined AAFT (IAAFT) data of two types (IAAFT-1 and IAAFT-2). The approach was applied to experimental protocols activating or blocking the sympathetic or parasympathetic branches of the autonomic nervous system or periodically perturbing cardiovascular control via paced respiration at different breathing rates. We found that short-term HPV was mostly linear at rest. Experimental protocols activating the sympathetic or parasympathetic nervous system did not produce non-linear dynamics. In contrast, paced respiration, especially at slow breathing rates, elicited significantly non-linear dynamics. Therefore, in short-term HPV ( approximately 300 beats) the use of non-linear models is not supported by the data, except under conditions whereby the subject is constrained to a slow respiratory rate.

Sympathetic overactivity in active ulcerative colitis: effects of clonidine.

Previous reports suggest that inflammatory bowel diseases may be accompanied by abnormalities in the neural autonomic profile. We tested the hypotheses that 1) an exaggerated sympathetic activity characterizes active ulcerative colitis (UC) and 2) a reduction of sympathetic activity by clonidine would be associated with clinical changes of UC. In 23 patients with UC and 20 controls, muscle sympathetic nerve activity (MSNA), ECG, blood pressure, and respiration were continuously recorded, and plasma catecholamine was evaluated both at rest and during a 75 degrees head-up tilt. Autonomic profile was assessed by MSNA, norepinephrine, epinephrine, spectral markers of low-frequency (LF) cardiac sympathetic (LF(RR); normalized units) and high-frequency (HF) parasympathetic (HF(RR); normalized units) modulation and sympathetic vasomotor control (LF systolic arterial pressure; LF(SAP)), obtained by spectrum analysis of the R-R interval and systolic pressure variability. Among UC patients, 16 agreed to be randomly assigned to 8-wk transdermal clonidine (15 mg/wk, 9 subjects), or placebo (7 patients). An autonomic profile, Disease Activity Index (DAI), and endoscopic pattern were compared before and after clonidine/placebo. At rest, MSNA, heart rate (HR), LF(RR), LF/HF, and LF(SAP) were higher and HF(RR) was lower in patients than in controls. Tilt decreased HF(RR) and increased MSNA and LF(RR) less in patients than in controls. Clonidine decreased HR, MSNA, epinephrine, LF(RR), and increased HF(RR), whereas placebo had no effects. Changes of the autonomic profile after clonidine were associated with reduction of DAI score. An overall increase of sympathetic activity characterized active UC. Normalization of the autonomic profile by clonidine was accompanied by an improvement of the disease.

Abnormalities of cardiovascular neural control and reduced orthostatic tolerance in patients with primary fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain. Symptoms of orthostatic intolerance may also be present, suggesting underlying abnormalities of cardiovascular neural regulation. We tested the hypothesis that FM is characterized by sympathetic overactivity and alterations in cardiovascular autonomic response to gravitational stimulus. METHODS: Sixteen patients with primary FM and 16 healthy controls underwent electrocardiography examination, finger blood pressure, respiration, and muscle sympathetic nerve activity (MSNA) recordings at rest and during stepwise tilt test, up to 75 degrees . The autonomic profile was assessed by MSNA, plasma catecholamine, and spectral indices of cardiac sympathetic (LFRR in normalized units, NU) and vagal (HFRR both in absolute and NU) modulation and of sympathetic vasomotor control (LFSAP) computed by spectrum analysis of RR and systolic arterial pressure (SAP) variability. Arterial baroreflex function was evaluated by the SAP/RR spontaneous-sequences technique, the index a, and the gain of MSNA/diastolic pressure relationship during stepwise tilt test. RESULTS: At rest, patients showed higher values of heart rate, MSNA, LFRR NU, LF/HF, LFSAP, and reduced HFRR than controls. During tilt test, lack of increase of MSNA, less decrease of HFRR, and excessive rate (44%) of syncope were found in patients, suggesting reduced capability to enhance the sympathetic activity to vessels and withdraw the vagal modulation to sino-atrial node. Baroreflex function was similar in both groups. CONCLUSION: Patients with FM have an overall enhancement of cardiovascular sympathetic activity while recumbent. Lack of increased sympathetic discharge to vessels and decreased cardiac vagal activity characterize their autonomic profile during tilt test, and might account for the excessive rate of syncope.

Symbolic dynamics of heart rate variability: a probe to investigate cardiac autonomic modulation.

BACKGROUND: Sympathetic and parasympathetic systems are considered the principal rapidly reacting systems that control heart rate. METHODS AND RESULTS: We propose a symbolic analysis series to quantify the prevalence of sympathetic or parasympathetic cardiac modulation. This analysis decomposes the heart rate variability series in patterns lasting 3 beats and classifies them into 3 categories: nonvariable, variable, and very variable patterns referred to as 0V, 1V, and 2V patterns. First, we applied this method to experimental and pharmacological conditions characterized by sympathetic activation (tilt test, handgrip, nitroprusside, and high-dose atropine administration) or parasympathetic activation (phenylephrine and low-dose atropine administration) in 60 healthy subjects. An increase in sympathetic modulation and a vagal withdrawal elicited a significant increase in 0V patterns and a decrease in 2V patterns, whereas parasympathetic dominance induced the opposite, reflecting a reciprocal sympathovagal balance. The second part of the study considered a series of 300 beats before the onset of major arrhythmic events in patients with an implantable cardioverter-defibrillator. Symbolic analysis detected an increase in the percentage of 0V patterns before the onset of major arrhythmias compared with baseline (41.6+/-3.9% and 24.4+/-2.9%, respectively; P<0.01), indicating a sympathetic prevalence. On the other hand, the 2V patterns did not decrease before major arrhythmias, suggesting the presence of nonreciprocal autonomic modulations. CONCLUSIONS: Symbolic analysis of 3 beat sequences takes into account the different time course of sympathetic and parasympathetic cardiac modulations and seems appropriate for elucidating the neural pathophysiological mechanisms occurring during the short periods that precede acute cardiac events.

Heart rate variability: from bench to bedside.

Power spectrum analysis of cardiovascular signal variability, and in particular of the RR period (heart rate variability, HRV), is a widely used methodology for investigating autonomic neural regulation in health and disease that can quantify the sympathovagal balance modulating the sinus node pacemaker. In some cases, it can also quantify the neural regulation of other organs or apparatuses. However, use of the correct methodology is crucial to extract the information embedded in the frequency domain. In numerous abnormal conditions, such as essential arterial hypertension, acute myocardial infarction and heart failure, the sympathovagal balance may be altered in basal conditions. However, a reduced responsiveness to an excitatory stimulus is the most common feature that characterizes numerous pathophysiological states. The attenuation of an oscillatory pattern can also reflect an altered target function, thus providing important prognostic markers. The general features of this approach correspond well to the needs of an internist attempting to envisage the involvement of the whole organism in a disease process.

Different spectral components of 24 h heart rate variability are related to different modes of death in chronic heart failure.

AIMS: To assess whether analysis of heart rate variability (HRV) from 24 h Holter recordings provides information about the mode of death (pump failure vs. sudden death) in chronic heart failure (CHF). METHODS AND RESULTS: We analysed 24 h HRV in 330 consecutive CHF patients in sinus rhythm. Indices derived from time domain, spectral domain, and fractal analyses of 24 h automatic HRV were evaluated. Data from clinical assessment, echocardiography, right heart catheterization, exercise test, blood biochemical examination, and arrhythmia pattern were analysed. Patients were followed up for 3 years. Two simple multivariable models, both including 24 h spectral indices, were able to identify patients at higher risk of progressive pump failure and sudden death, respectively. Depressed power of night-time HRV (< or = 509 ms(2)) below 0.04 Hz [very low frequency (VLF)], high pulmonary wedge pressure (PWP > or = 18 mm Hg) and low left ventricular ejection fraction (LVEF < or = 24%) were independently related to death for progressive pump failure, while the reduction of power between 0.04 and 0.15 Hz at night (LF < or = 20 ms(2)) and increased left ventricular end-systolic diameter (LVESD > or = 61 mm) were linked to sudden mortality. CONCLUSION: Automatic spectral analysis of 24 h HRV provides independent risk indices related to mode of death in sinus rhythm CHF patients.

Acute beta-blockade increases muscle sympathetic activity and modifies its frequency distribution.

BACKGROUND: The possible mechanisms by which beta-adrenergic antagonists may act on the neural regulation of the cardiovascular system are still elusive. Recent studies reported a marked increase of postganglionic muscle sympathetic nerve activity (MSNA) after acute beta-blockade associated with unchanged values of arterial blood pressure and baroreflex sensitivity. We tested the hypothesis that acute beta-blockade might also alter the oscillatory characteristics of MSNA, thus decreasing its effectiveness on peripheral vasoconstriction. METHODS AND RESULTS: In 11 healthy volunteers, ECG, MSNA, arterial pressure, and respiration were recorded before and after atenolol (0.05 mg/kg IV bolus) administration. The frequency distribution of RR interval, MSNA, systolic arterial pressure (SAP), and respiratory variability was assessed by spectrum and cross-spectrum analysis. Spontaneous baroreflex sensitivity (alpha-index) and plasma catecholamines (high-performance liquid chromatography) were measured. Atenolol induced a significant increase in RR interval (14.3+/-1.6%) with no changes in systolic and diastolic arterial pressure. MSNA increased (42+/-13% from 18+/-2 bursts per minute). The low-frequency (LF) component of RR and MSNA variability decreased (-44+/-7% and -24+/-5%, respectively), whereas the high-frequency (HF) component increased (163+/-55% and 34+/-11%, respectively), expressed in normalized units. Spectral coherence, an index of oscillatory coupling, decreased between LF(RR) and LF(MSNA), whereas it increased between HF(MSNA) and HF(Resp). SAP variability, alpha-index, and plasma catecholamines remained unchanged. CONCLUSIONS: Atenolol induced a change in MSNA frequency distribution reflecting a stronger respiratory coupling. This shift toward high frequency, despite an increase in MSNA, may lead to a less efficient sympathetic vasomotor modulation.

Altered profile of baroreflex and autonomic responses to lower body negative pressure in chronic orthostatic intolerance.

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.

Sympathetic overactivity in ischaemic heart disease.

The efficacy of pharmacological beta-blockade in decreasing cardiac death in patients after myocardial infarction suggests the existence of sympathetic overactivity and indicates the importance of assessing its magnitude. The paper by Graham and co-workers in this issue of Clinical Science has attempted to address this issue by measuring muscle sympathetic nerve activity (MSNA) in various groups of patients and control subjects. It was found that, after myocardial infarction, there was sympathetic overactivity, which was more marked and more long-lasting than after unstable angina, whereas, in the presence of simple coronary artery disease, sympathetic activity did not differ from that in control subjects. Clear signs of sympathetic overactivity lasting for months after an acute myocardial infarction have already been reported using quite different methodology, i.e. spectral analysis of heart period and systolic arterial pressure variability. The soundest hypothesis to explain such a sympathetic overactivity appears to be based on the well-demonstrated finding that the ischaemic heart is a powerful site of origin of both excitatory and/or inhibitory reflexes, which may be of paramount clinical importance.

Impairment in cardiac autonomic regulation preceding arterial hypertension in humans: insights from spectral analysis of beat-by-beat cardiovascular variability.

BACKGROUND: Subjects in the upper-normal range of arterial pressure have an excess cardiovascular risk, which suggests that other factors, such as impaired autonomic regulation, might be implicated. This study was designed to assess whether noninvasive markers of cardiac and vascular autonomic regulation might already be altered in subjects with high-normal arterial pressure levels. METHODS AND RESULTS: We performed an observational study on a population comprising 300 subjects of both sexes with arterial pressure ranging from 90/60 to 210/120 mm Hg, who were divided into 3 groups (each n=100) with average systolic pressures of 103, 133, and 163 mm Hg. Autonomic regulation was inferred from spectral analysis of RR interval and systolic arterial pressure variability, considering rest and stand-induced changes, to account for sympathetic excitatory components. Significant alterations in markers of sinoatrial regulation (increased low-frequency normalized units, reduced high-frequency normalized units, and alpha-index) were already apparent in subjects in the second tertile, ie, those with arterial pressure within normal limits. Markers of vascular regulation instead showed significant alterations in the third (hypertensive) tertile. In response to standing, changes in markers of sinoatrial modulations were gradually reduced, whereas those of vascular regulation were increased. A tight link between progression of arterial pressure and the continuum of changes in autonomic markers as shown by simple correlation analysis appeared strongly affected by age and was spread across many spectral analysis-derived variables. Hypertensive autonomic dysregulation was particularly apparent in the youngest group. CONCLUSIONS: RR-variability parameters might prove useful to assess, with longitudinal studies, the mechanistic role of autonomic impairment in the increased risk of prehypertensive conditions.

Heart rate variability as a clinical tool.

Power spectrum analysis of cardiovascular signal variability, and in particular of the RR period (heart rate variability), is a widely used procedure for the investigation of autonomic cardiovascular control and/or target function impairment. However, a correct methodology is essential to extract the information embedded in the frequency domain. This article has the main purpose of proposing a still wider clinical use of the spectral methodology. Indeed, with this procedure the state of the sympathovagal balance modulating the sinus node pacemaker activity can be quantified in a variety of physiological and pathophysiological conditions. Changes in the sympathovagal balance can be often detected in basal conditions; however, a reduced responsiveness to an excitatory stimulus is the most common feature that characterizes numerous pathophysiological states. Moreover, the attenuation of an oscillatory pattern or its impaired responsiveness to a given stimulus can also reflect an altered target function and thus can furnish interesting prognostic markers.