Myocardial involvement in anti-phospholipid syndrome: Beyond acute myocardial infarction.

Anti-phospholipid antibodies (aPL) are the serological biomarkers of anti-phospholipid syndrome (APS), an autoimmune disorder characterized by vascular events and/or pregnancy morbidity. APS is a unique condition as thrombosis might occur in arterial, venous or capillary circulations. The heart provides a frequent target for circulating aPL, leading to a wide variety of clinical manifestations. The most common cardiac presentation in APS, valvular involvement, acknowledges a dual etiology comprising both microthrombotic and inflammatory mechanisms. We describe the cases of 4 patients with primary APS who presented a clinically manifest myocardiopathy without epicardial macrovascular distribution. We propose that microthrombotic/inflammatory myocardiopathy might be an overlooked complication of high-risk APS. As extensively hereby reviewed, the literature provides support to this hypothesis in terms of anecdotal case-reports, in some cases with myocardial bioptic specimens. In aPL-positive subjects, microthrombotic/inflammatory myocardial involvement might also clinically manifest as dilated cardiomyopathy, a clinical entity characterized by ventricular dilation and reduced cardiac output. Furthermore, microthrombotic/inflammatory myocardial involvement might be subclinical, presenting as diastolic dysfunction. Currently, there is no single clinical or imaging finding to firmly confirm the diagnosis; an integrated approach including clinical history, clinical assessment, laboratory tests and cardiac magnetic resonance should be pursued in patients with suggestive clinical presentation.

Sex and acetazolamide effects on chemoreflex and periodic breathing during sleep at altitude.

OBJECTIVE: Nocturnal periodic breathing occurs more frequently in men than in women with various clinical and pathophysiologic conditions. The mechanisms accounting for this sex-related difference are not completely understood. Acetazolamide effectively counteracts nocturnal periodic breathing, but it has been investigated almost exclusively in men. Our aim was to explore possible determinants of nocturnal periodic breathing in a high-altitude setting both in men and in women. We hypothesized that increased hypoxic chemosensitivity in men could be associated with the development of nocturnal periodic breathing at altitude more frequently than in women, and that acetazolamide, by leftward shifting the CO2 ventilatory response, could improve nocturnal periodic breathing at altitude in a sex-independent manner. METHODS: Forty-four healthy lowlanders (21 women), randomized to acetazolamide or placebo, underwent cardiorespiratory sleep studies at sea level off treatment and under treatment on the first night after arrival at a 4,559-m altitude. Hypoxic and hypercapnic chemosensitivities were assessed at sea level. RESULTS: Men, more frequently than women, exhibited increased hypoxic chemosensitivity and displayed nocturnal periodic breathing at altitude. Acetazolamide leftward shifted the CO2 set point and, at altitude, improved oxygenation and reduced periodic breathing in both sexes, but to a larger extent in men. Hypoxic chemosensitivity directly correlated with the number of apneas/hypopneas at altitude in the placebo group but not in the acetazolamide group. CONCLUSIONS: The greater severity of periodic breathing during sleep displayed by men at altitude could be attributed to their increased hypoxic chemosensitivity. Acetazolamide counteracted the occurrence of periodic breathing at altitude in both sexes, modifying the apneic threshold and improving oxygenation. TRIAL REGISTRY: EU Clinical Trials Register, EudraCT; No.: 2010-019986-27; URL: https://www.clinicaltrialsregister.eu.

Effects of beta-blockade on exercise performance at high altitude: a randomized, placebo-controlled trial comparing the efficacy of nebivolol versus carvedilol in healthy subjects.

AIMS: Exposure to high altitude (HA) hypoxia decreases exercise performance in healthy subjects. Although ß-blockers are known to affect exercise capacity in normoxia, no data are available comparing selective and nonselective ß-adrenergic blockade on exercise performance in healthy subjects acutely exposed to HA hypoxia. We compared the impact of nebivolol and carvedilol on exercise capacity in healthy subjects acutely exposed to HA hypobaric hypoxia. METHODS: In this double-blind, placebo-controlled trial, 27 healthy untrained sea-level (SL) residents (15 males, age 38.3 ± 12.8 years) were randomized to placebo (n = 9), carvedilol 25 mg b.i.d. (n = 9), or nebivolol 5 mg o.d. (n = 9). Primary endpoints were measures of exercise performance evaluated by cardiopulmonary exercise testing at sea level without treatment, and after at least 3 weeks of treatment, both at SL and shortly after arrival at HA (4559 m). RESULTS: HA hypoxia significantly decreased resting and peak oxygen saturation, peak workload, VO(2) , and heart rate (HR) (P < 0.01). Changes from SL (no treatment) differed among treatments: (1) peak VO(2) was better preserved with nebivolol (-22.5%) than with carvedilol (-37.6%) (P < 0.01); (2) peak HR decreased with carvedilol (-43.9 ± 11.9 beats/min) more than with nebivolol (-24.8 ± 13.6 beats/min) (P < 0.05); (3) peak minute ventilation (VE) decreased with carvedilol (-9.3%) and increased with nebivolol (+15.2%) (P= 0.053). Only peak VE changes independently predicted changes in peak VO(2) at multivariate analysis (R= 0.62, P < 0.01). CONCLUSIONS: Exercise performance is better preserved with nebivolol than with carvedilol under acute exposure to HA hypoxia in healthy subjects.

Effects of selective and nonselective beta-blockade on 24-h ambulatory blood pressure under hypobaric hypoxia at altitude.

BACKGROUND: Little is known about the effects of cardiovascular drugs at high altitude. OBJECTIVE: To assess 24-h blood pressure (BP) and heart rate (HR) during short-term altitude exposure in healthy normotensive persons treated with carvedilol or nebivolol. METHODS: Participants were randomized in double-blind to placebo, nebivolol 5 mg once daily or carvedilol 25 mg b.i.d. Tests were performed at sea level (baseline and after 2 weeks treatment) and on second to third day at altitude (Monte Rosa, 4559 m), still on treatment. Data collection included conventional BP, 24-h ambulatory BP monitoring (ABPM), oxygen saturation (SpO2), Lake Louise Score and adverse symptoms score. RESULTS: Twenty-four participants had complete data (36.4 ± 12.8 years, 14 men). Both beta-blockers reduced 24-h BP at sea level. At altitude 24-h BP increased in all groups, mainly due to increased night-time BP. Twenty-four-hour SBP at altitude was lower with carvedilol (116.4 ± 2.1 mmHg) than with placebo (125.8 ± 2.2 mmHg; P < 0.05) and intermediate with nebivolol (120.7 ± 2.1 mmHg; NS vs. others). Rate of nondipping increased at altitude and was lower with nebivolol than with placebo (33 vs. 71%; P = 0.065). Side effects score was higher with carvedilol than with placebo (P = 0.04), and intermediate with nebivolol. SpO2 at altitude was higher with placebo (86.1 ± 1.2%) than with nebivolol (81.7 ± 1.1%; P = 0.07) or carvedilol (81.1 ± 1.1%; P = 0.04). CONCLUSIONS: Both carvedilol and nebivolol partly counteract the increase in BP at altitude in healthy normotensive individuals but are associated with a lower SpO2. Carvedilol seems more potent in this regard, whereas nebivolol more effectively prevents the shift to a nondipping BP profile and is better tolerated.

Continuous positive airway pressure increases haemoglobin O2 saturation after acute but not prolonged altitude exposure.

AIMS: It is unknown whether subclinical high-altitude pulmonary oedema reduces spontaneously after prolonged altitude exposure. Continuous positive airway pressure (CPAP) removes extravascular lung fluids and improves haemoglobin oxygen saturation in acute cardiogenic oedema. We evaluated the presence of pulmonary extravascular fluid increase by assessing CPAP effects on haemoglobin oxygen saturation under acute and prolonged altitude exposure. METHODS AND RESULTS: We applied 7 cm H(2)O CPAP for 30 min to healthy individuals after acute (Capanna Margherita, CM, 4559 m, 2 days permanence, and <36 h hike) and prolonged altitude exposure (Mount Everest South Base Camp, MEBC, 5350 m, 10 days permanence, and 9 days hike). At CM, CPAP reduced heart rate and systolic pulmonary artery pressure while haemoglobin oxygen saturation increased from 80% (median), 78-81 (first to third quartiles), to 91%, 84-97 (P < 0.001). After 10 days at MEBC, haemoglobin oxygen saturation spontaneously increased from 77% (74-82) to 86% (82-89) (P < 0.001) while heart rate (from 79, 64-92, to 70, 54-81; P < 0.001) and respiratory rate (from 15, 13-17, to 13, 13-15; P < 0.001) decreased. Under such conditions, these parameters were not influenced by CPAP. CONCLUSION: After ascent excessive lung fluids accumulate affecting haemoglobin oxygen saturation and, in these circumstances, CPAP is effective. Acclimatization implies spontaneous haemoglobin oxygen saturation increase and, after prolonged altitude exposure, CPAP is not associated with HbO(2)-sat increase suggesting a reduction in alveolar fluids.

Variables influencing heart rate.

In both physiologic and pathological conditions, instantaneous heart rate value is the result of a rather complex interplay. It constantly varies under the influence of a number of factors: nonmodifiable and modifiable ones. Pharmacologic blockade with beta-adrenergic antagonists and/or with parasympathetic antagonists such as atropine have permitted the identification of the mechanisms of autonomic nervous regulation of heart rate in a variety of physiologic and pathological conditions. The analysis of heart rate and blood pressure variability has yielded additional information on the autonomic control of the circulation, which has proven to have diagnostic and prognostic implications in a number of clinically relevant conditions such as hypertension, acute myocardial infarction, heart failure, and predisposition to sudden cardiac death. This article will summarize, based on available epidemiologic and clinical studies, the key variables influencing heart rate and heart rate variability in view of the known association between heart rate and cardiovascular disease.

Impact of telemonitoring at home on the management of elderly patients with congestive heart failure.

We studied the effects of home telemonitoring in elderly patients with congestive heart failure (CHF) on mortality and rate of hospitalization, compliance with treatment, quality of life and costs of CHF management, by comparison with a group receiving usual care. Fifty-seven elderly CHF patients were randomized to standard care or to home telemonitoring-based care and followed for 12 months. In the subjects who were monitored, weekly reports on their clinical status were obtained and their management was modified accordingly. Home telemonitoring was associated with improvements in the composite endpoint of mortality and rate of hospitalizations (P = 0.006), a better compliance with therapy, more frequent use of beta-blockers and statins, lower total cholesterol level and a better reported health perception score. The improved results with home telemonitoring in CHF were probably due to better compliance and to closer monitoring of the patients.

Disappearance of isocapnic buffering period during increasing work rate exercise at high altitude.

BACKGROUND: At sea level, ventilation kinetics are characterized during a ramp exercise by three progressively steeper slopes, the first from the beginning of exercise to anaerobic threshold, the second from anaerobic threshold to respiratory compensation point, and the third from respiratory compensation point to peak exercise. In the second ventilation phase, body CO2 stores are used to buffer acidosis owing to lactate production; it has been suggested that this extra CO2 production drives the ventilation increase. At high altitude, ventilation increases owing to hypoxia. We hypothesize that ventilation increase reduces body CO2 stores affecting ventilation kinetics during exercise. DESIGN: In eight healthy participants, we studied the ventilation kinetics during an exercise performed at sea level and at high altitude (4559 m). METHODS: We used 30 W/2 min step incremental protocol both at sea level and high altitude. Tests were done on a cyclo-ergometer with breath-by-breath ventilation and inspiratory and expiratory gas measurements. We evaluated cardiopulmonary data at anaerobic threshold, respiratory compensation point, peak exercise and the VE/VCO2 slope. RESULTS: At high altitude: (a) peak VO2 decreased from 2595+/-705 to 1745+/-545 ml/min (P<0.001); (b) efficiency of ventilation decreased (VE/VCO2 slope from 25+/-2 to 38+/-4, P<0.0001); (c) at each exercise step end-tidal pressure change for CO2 was lower; and (d) the isocapnic buffering period disappeared in seven over eight participants and was significantly shortened in the remaining participant. CONCLUSION: Exercise performed at high altitude is characterized by two, instead of three, ventilation slopes.

Italian society of hypertension guidelines for conventional and automated blood pressure measurement in the office, at home and over 24 hours.

This article offers instructions and recommendations on how to perform blood pressure measurements in the doctor's office, in the patient's home and in ambulatory conditions over 24 hours. Great attention is paid to some of the general aspects of blood pressure measurement, including the accuracy of blood pressure measuring devices, the importance of a 'white-coat effect', and the need for patient education. This article also deals with a number of practical details, such as the importance of patient's relaxation and position, arm position and support, arm selection and cuff selection and application. Recommendations are provided on the observer's position and performance, and on the need to pay attention to specific factors affecting the blood pressure measurement in different patient populations, namely in children, elderly and obese people, pregnant women, patients with arrhythmias and patients on treatment. This article then separately focuses on the characteristics of auscultatory and automated measurements, the latter performed either in the office, at home or over 24 hours in ambulatory settings. Home blood pressure monitoring (HBPM) is becoming increasingly important in the diagnosis and management of arterial hypertension. The importance of HBPM in cardiovascular prevention, related to a deeper involvement of patients in their long-term management, and the wide diffusion of this approach in populations, is not always accompanied by adequate knowledge of how to make proper use of this technique, which emphasizes the need for more precise recommendations. This article summarizes the available evidence and provides recommendations on the use of home blood pressure monitoring in clinical practice and in research. It updates the previous recommendations on the same topic issued in 2000. The main topics addressed include the methodology of HBPM, focusing on measurement conditions and procedures, ranging from patient/subject position, to arm selection, arm position and support, cuff selection and application and data reporting, diagnostic and therapeutic thresholds, clinical applications in hypertension (with specific reference to special populations) and its applications in research. Special attention is given to device validation and selection as well as to patient education and to the need of HBPM to be guided by the physician in charge. The final section deals with the problems related to the implementation of these recommendations in clinical practice. Finally, the methodology and clinical impact of 24-hour ambulatory blood pressure monitoring are also addressed in detail, focusing on the parameters that can be derived from the analysis of 24-hour blood pressure recordings applied both to the diagnostic and prognostic evaluation of hypertensive patients and to the assessment of the effectiveness of antihypertensive treatment in controlling blood pressure through the day and night. Instructions to users on how to properly perform HBPM are provided as an appendix.

Do we need out-of-office blood pressure in every patient?

PURPOSE OF REVIEW: The limitations affecting office blood pressure readings have spurred the development of techniques for measuring blood pressure out of a clinical environment. The increasing use of home and ambulatory blood pressure monitoring has allowed the identification of specific blood pressure patterns related either to a discrepancy between office and out-of-office blood pressure or to alterations in the 24-h blood pressure profiles. This review offers an update on the most recent data published on the above issues. RECENT FINDINGS: A critical overview is provided on recent data published on blood pressure patterns suggested to have clinical relevance. These include white coat hypertension, the so-called masked hypertension, enhanced overall blood pressure variability over 24 h, a steeper morning blood pressure surge and a blunted or an excessive blood pressure fall at night. SUMMARY: All of these different conditions have been variably reported to carry prognostic implications, and may represent specific targets for antihypertensive treatment. Their identification and management require information on out-of-office blood pressure, which suggests that self blood pressure monitoring at home or 24-h ambulatory blood pressure monitoring should be used more frequently in clinical practice, following the indications issued in recent guidelines.

Blood pressure variability: its measurement and significance in hypertension.

Blood pressure (BP) fluctuations over time physiologically result from the complex interaction between environmental stimulation, genetic factors, and cardiovascular control mechanisms. Ambulatory BP-monitoring techniques, in particular systems providing beat-by-beat BP recording, have allowed a detailed description of the different components contributing to overall BP variability (BPV) over 24 hours, including short-lasting and more sustained BP changes. In hypertension, BPV increases with increasing BP levels, and evidence is available that its magnitude correlates closely with target-organ damage and with the incidence of cardiovascular events, independent of absolute BP levels. It has been suggested that drugs capable of providing smooth 24-hour BP control, reducing BPV, may confer additional target-organ protection. Mathematic indices, such as the trough-to-peak ratio and the smoothness index, represent useful measures of the homogeneity of the antihypertensive effect over 24 hours. Further studies are still needed to confirm that, in humans, interventions that can reduce BPV can also reduce the rate of cardiovascular events.

HEARTFAID: A knowledge based platform of services for supporting medical-clinical management of heart failure within elderly population.

HEARTFAID is a research and development project aimed at devising, developing and validating an innovative knowledge based platform of services, able to improve early diagnosis and to make more effective the medical-clinical management of heart diseases within elderly population. Chronic Heart Failure is one of the most remarkable health problems for prevalence and morbidity, especially in the developed western countries, with a strong impact in terms of social and economic effects. All these aspects are typically emphasized within the elderly population, with very frequent hospital admissions and a significant increase of medical costs. Recent studies and experiences have demonstrated that accurate heart failure management programs, based on a suitable integration of inpatient and outpatient clinical procedures, might prevent and reduce hospital admissions, improving clinical status and reducing costs. HEARTFAID aims at defining efficient and effective health care delivery organization and management models for the "optimal" management of the care in the field of cardiovascular diseases. The HEARTFAID innovative computerized system will improve the processes of diagnosis, prognosis and therapy provision, providing the following services: * electronic health record for easy and ubiquitous access to heterogeneous patients data;* integrated services for healthcare professionals, including patient telemonitoring, signal and image processing, alert and alarm system;* clinical decision support in the heart failure domain, based on pattern recognition in historical data, knowledge discovery analysis and inferences on patients' clinical data.The formalization of the pre-existing clinical knowledge and the discovery of new elicited knowledge represent the core of the HEARTFAID platform.

Hypertension prevalence, awareness, control and association with metabolic abnormalities in the San Marino population: the SMOOTH study.

BACKGROUND: The aim of the SMOOTH (San Marino Observational Outlooking Trial on Hypertension) study was to explore hypertension awareness, treatment and control and the associated metabolic abnormalities and risk factors in the population of San Marino, a small state in the Mediterranean area, for which limited evidence is available. METHODS: Nine general practitioners enrolled 4590 consecutive subjects (44% of the San Marino population age 40-75 years), seen in their office by collecting history, physical and laboratory data and office blood pressure (BP) measurements. RESULTS: Of these subjects, 2446 were normotensive and 2144 hypertensive; 62.3% of hypertensive patients were aware of their condition, 58.6% were treated (monotherapy 31.5%, combination therapy 27.1%), and 21.7% were controlled. Hypertension awareness and treatment were more frequent above age 50 and in females; BP control was similarly low in both genders. As compared to normotensives, hypertensive subjects were less frequently smokers (20.1 versus 27.8%), had greater body mass index (28.1 +/- 4.5 versus 25.8 +/- 3.7 g/m), and a higher prevalence of diabetes mellitus (15.8 versus 6.3%), lower high-density lipoprotein (HDL) cholesterol and higher prevalence of increased blood total cholesterol (66.1 versus 51.3%), triglycerides and serum uric acid. Values of subjects with 'high-normal' blood pressure were closer to those of hypertensive subjects. The prevalence of metabolic syndrome was higher in hypertensive than in normotensive subjects, and in treated than in untreated hypertensives. CONCLUSIONS: Even in a small Mediterranean country with high health-care standards, hypertension awareness, treatment and control are inadequate and hypertension clusters with metabolic abnormalities and risk factors as in non-Mediterranean areas.

[Coronary flow reserve assessment by transthoracic color Doppler echocardiography after primary angioplasty: relationship with recovery of left ventricular function]. / Valutazione della riserva di flusso coronarico mediante ecocardiografia color Doppler transtoracica in pazienti sottoposti ad angioplastica primaria: relazioni con il recupero della funzione ventricolare sinistra.

BACKGROUND: The aim of this study was to determine the relationship between coronary flow reserve measurement by transthoracic Doppler echocardiography in recent acute myocardial infarction treated with primary coronary angioplasty (PTCA) and recovery of left ventricular function. METHODS: Forty-one consecutive patients (3 patients excluded for not good quality of the Doppler signal) have been studied with: (1) recent first acute myocardial infarction treated with primary PTCA within 6 hours of pain onset; (2) optimal angioplasty result with stent deployment, anti-IIb/IIIa infusion and TIMI 3 flow; (3) lack of type 1 diabetes and/or hypertension; (4) good tolerance to adenosine. Transthoracic Doppler echocardiography was used to record coronary flow velocities in the distal left anterior descending and posterior descending coronary arteries at rest and after infusion of adenosine. Coronary flow reserve was measured after 11 +/- 1 days from the acute event. The wall motion score index (WMSI) was calculated at baseline, 1 month and 3 months from myocardial infarction. RESULTS: Patients of group A (n = 29 with coronary flow reserve > or = 1.6) showed a progressive and significant recovery of left ventricular function at follow-up. Patients of group B (n = 9 with coronary flow reserve < 1.6) had persistent left ventricular dysfunction at 3 months (ANOVA, p < 0.0001). WMSI was 1.64 +/- 0.26 in group A and 1.81 +/- 0.16 in group B (p = 0.09) at baseline; 1.30 +/- 0.26 in group A and 1.75 +/- 0.16 in group B (p < 0.0001) at 1 month; and 1.20 +/- 0.25 in group A and 1.73 +/- 0.17 in group B at 3 months. There was an inverse correlation between coronary flow reserve and WMSI at 1 month (r = -0.564, p < 0.0001), and at 3 months (r = -0.583, p < 0.0001). On multivariate analysis baseline WMSI and coronary flow reserve were the only predictors of 1-month WMSI recovery and of WMSI recovery at 3 months. CONCLUSIONS: Coronary flow reserve by transthoracic color Doppler echocardiography is a useful method for predicting left ventricular function recovery in patients after primary PTCA.

[Complexity of observable psychological distress after surgical myocardial revascularization in male subjects]. / Complessità dei disturbi psicologici osservabili dopo rivascolarizzazione miocardica chirurgica in soggetti di sesso maschile.

BACKGROUND: Psychological disturbances like anxiety, depression, post-traumatic stress disorder are often associated with coronary artery disease and, in some studies, play a prognostic role after a coronary event. Despite some psychological disturbances following coronary artery bypass graft (CABG) have an impact on outcomes of both the surgical intervention and the rehabilitation program, their complexity as well as their clinical and instrumental determinants are still not fully understood. The aim of this study was to determine in male subjects with coronary artery disease the prevalence and complexity of psychological disturbances occurring after CABG as well as their predictors. METHODS: One hundred eighteen males without history of psychological disturbances consecutively admitted to our rehabilitation inpatient service between September 2002 and September 2003 underwent 11 +/- 2 days after CABG extensive psychometric testing including the Minnesota Multiphasic Personality Inventory-2, the Cognitive Behavioral Assessment.2, and the Hamilton test. Cardiac evaluation included coronary risk factors, NYHA class, coronary heart disease history, medical therapy, CABG number, and echocardiography. RESULTS: Mean age 63.7 +/- 8.1 years; ejection fraction 54.6 +/- 10.3%; NYHA class I 92.4%, NYHA class II and III 7.6%; CABG number 1 (11%), 2 (23.7%), 3 (39.8%), 4 (21.8%), 5 (4.2%); coronary artery disease length 64 +/- 85 months, hospital stay 31.3 +/- 8 days. The score was above clinical cut-off on scale for depression in 16-39.8% of the patients, state anxiety in 27.1%, trauma in 16.1%, type A personality in 16.1%. Subjects above clinical cut-off for depression, anxiety and trauma did not differ from subjects below in terms of clinical and instrumental characteristics. Age, ejection fraction, coronary risk factors, coronary heart disease duration, and CABG number did not predict the development of depression, anxiety and trauma. Psychological disturbances often clustered in the same subjects. CONCLUSIONS: In males following CABG, psychological disturbances are extremely frequent, often clustered, and independent of subjects' characteristics and coronary heart disease severity.

[How to write a scientific paper]. / Come scrivere un articolo scientifico.

To write a paper and to succeed in getting it published in a highly renowned scientific journal represent the last but not the least of the difficulties that a researcher has to face before being able to consider a given research project fully accomplished. While writing a manuscript, it is important to put a consistent effort in designing its structure, paying attention to a few technical guidelines. It is worth keeping in mind, however, that the editorial success of a manuscript is related not only to the writer skills and experience but also to the attention previously dedicated to the design and conduction of the research project from which data are derived. On the other hand, the probability for a well designed and carefully performed study (yielding data relevant from a clinical viewpoint), to have its results accepted for publication in an important journal is very low if they are poorly summarized in a low quality paper. In the light of these considerations, the aim of this concise review was to provide the researcher with a few simple tips on how to prepare a scientific article, ranging from its early drafting to its final publication. We have also dealt in some detail with the problems related to the selection of the journal and manuscript format, with the procedures related to manuscript submission, and with the approach to follow in order to prepare a proper answering to the reviewers' and editors' comments.

Attenuation of haemodynamic, metabolic and energy expenditure responses to isoproterenol in patients with hypertension.

OBJECTIVE: Overweight and heightened sympathetic activity are more common in hypertensive than normotensive subjects. beta-adrenoceptor down-regulation has been described in hypertension. We tested the hypothesis that chronic sympathetic overactivity impairs beta-adrenergic-mediated thermogenesis and thereby favours gain of weight in hypertension. PARTICIPANTS: The study included 13 hypertensive subjects aged 35.3 +/- 7.9 years and 25 normotensive subjects of control of similar age. METHODS: To measure beta-adrenergically mediated haemodynamic, metabolic and thermogenic responsiveness, increasing doses of isoproterenol diluted in 2.5 ml saline were injected as intravenous boluses (0.1, 0.25, 0.5, 1.0 and 2.0 microg/m). On a separate day, isoproterenol was infused continuously intravenously in increasing doses (10, 20 and 40 ng/kg per min), each dose for 30 min. RESULTS: The sitting heart rate and body mass were greater in hypertensives (P = 0.000, and P = 0.005, respectively). The heart rate responses to 1 and 2 microg/m isoproterenol bolus (P = 0.01 and P = 0.03, respectively) were reduced in hypertensives. The energy expenditure (P = 0.002) and oxygen consumption (P = 0.0004) increase with 40 ng/kg per min isoproterenol infusion, and glucose and phosphate responses at both 20 (P = 0.01 and P = 0.05) and 40 (P = 0.001 and P = 0.02) ng/kg per min isoproterenol infusion were attenuated in hypertensives. The baseline heart rate negatively correlated with heart rate (P = 0.015) response to isoproterenol bolus and blood pressure (P = 0.02) response to isoproterenol infusion. The urinary noradrenaline negatively correlated with heart rate response to isoproterenol bolus (P = 0.001), and with systolic blood pressure (P = 0.02) and energy expenditure responsiveness to isoproterenol infusion (P = 0.04). Furthermore, plasma noradrenaline negatively correlated with heart rate responsiveness to isoproterenol bolus (P = 0.004). CONCLUSIONS: These results show a generalized decrease of beta-adrenergic responsiveness in stage 1 hypertension and support the concept that sympathetic overactivity, via down-regulation of beta-adrenoceptor-mediated thermogenic responses, may facilitate the development of obesity in hypertension.