Gianluca Caldara

Weather-Related Changes in 24-Hour Blood Pressure Profile. Effects of Age and Implications for Hypertension Management

A downward titration of antihypertensive drug regimens in summertime is often performed on the basis of seasonal variations of clinic blood pressure (BP). However, little is known about the actual interaction between outdoor air temperature and the effects of antihypertensive treatment on ambulatory BP. The combined effects of aging, treatment, and daily mean temperature on clinic and ambulatory BP were investigated in 6404 subjects referred to our units between October 1999 and December 2003. Office and mean 24-hour systolic BP, as well as morning pressure surge, were significantly lower in hot (>90th percentiles of air temperature; 136±19, 130±14, and 33.3±16.1 mm Hg; P<0.05 for all), and higher in cold (<10th percentiles) days (141±12, 133±11, and 37.3±9.5 mm Hg; at least P<0.05 for all) when compared with intermediate days (138±18, 132±14, and 35.3±15.4 mm Hg). At regression analysis, 24-hour and daytime systolic pressure were inversely related to temperature (P<0.01 for all). Conversely, nighttime systolic pressure was positively related to temperature (P<0.02), with hot days being associated with higher nighttime pressure. Air temperature was identified as an independent predictor of nighttime systolic pressure increase in the group of elderly treated hypertensive subjects only. No significant relationship was found between air temperature and heart rate. Our results show for the first time that hot weather is associated with an increase in systolic pressure at night in treated elderly hypertensive subjects. This may be because of a nocturnal BP escape from the effects of a lighter summertime drug regimen and may have important implications for seasonal modulation of antihypertensive treatment.

A new method for assessing 24-h blood pressure variability after excluding the contribution of nocturnal blood pressure fall.

Objectives To assess quantitatively the relationship between nocturnal blood pressure (BP) fall and 24-h BP variability; to propose a new method for computing 24-h BP variability, devoid of the contribution from nocturnal BP fall; and to verify the clinical value of this method. Methods and results We analysed 3863 ambulatory BP recordings, and computed: (1) the standard deviation (SD) of 24-h BP directly from all individual readings and as a weighted mean of daytime and night-time SD (wSD); and (2) the size of nocturnal BP fall. Left ventricular mass index (LVMI) was assessed by echocardiography in 339 of the patients. The 24-h SD of BP was significantly greater than the 24-h wSD. Nocturnal BP fall was strongly and directly related to 24-h SD, the relationship with 24-h wSD being much weaker and inverse. The difference between SD and wSD was almost exclusively determined by the size of nocturnal BP fall. wSD of systolic BP was significantly related to LVMI, while 24-h SD was not. Conclusion Conventional 24-h SD of BP is markedly influenced by nocturnal BP fall. The weighted 24-h SD of BP removes the mathematical interference from night-time BP fall and correlates better with end-organ damage, therefore it may be considered as a simple index of 24-h BP variability superior to conventional 24-h SD.

Validation of the Omron M5-I, R5-I and HEM-907 automated blood pressure monitors in elderly individuals according to the International Protocol of the European Society of Hypertension.

ObjectiveThis study aimed at verifying the accuracy of three automated electronic oscillometric blood pressure measuring devices, namely Omron M5-I (home use upper arm monitor), R5-I (home use wrist monitor) and HEM-907 (professional use upper arm monitor) according to the European Society of Hypertension International Protocol in elderly individuals. MethodsSequential measurements of systolic and diastolic blood pressure were obtained in 33 participants (aged ≥75 years) using the mercury sphygmomanometer (two observers) and each of the tested devices (one supervisor). A standard adult cuff was always employed during the study because all participants had an arm circumference compatible with such a cuff. According to the European Society of Hypertension validation protocol 99 couples (three pairs per patient) of test device and reference blood pressure measurements were obtained during phase 1 (15 participants studied) and phase 2 (a further 18 participants) for each electronic monitor. ResultsAll devices successfully passed the validation study with a mean (±SD) device−observer difference for systolic and diastolic blood pressure of 0.2±3.6/0.2±3.9 mmHg (Omron M5-I), −1.5±6.2/−0.7±3.7 mmHg (Omron R5-I), and 0.1±5.1/−1.9±4.2 mmHg (Omron HEM-907). SD of the mean difference was lower and thus the precision was better for diastolic than for systolic blood pressure, and for the Omron M5-I than for the other two devices. ConclusionsAccording to the results of the validation study based on the European Society of Hypertension International Protocol the Omron M5-I, R5-I, and HEM-907 may be recommended for clinical use in elderly individuals, without atrial fibrillation or frequent ectopic beats.

Assessment of overall blood pressure variability and its different components

Blood pressure (BP) is characterized by continuous fluctuations, including fast changes lasting only a few seconds as well as slower and more prolonged variations, with a time constant of minutes or hours. Assessing the relative contribution of these different components to overall blood pressure variance is now possible through a number of mathematical approaches, either in the time or in the frequency domain (spectral analysis). Due to its complex nature, a precise and detailed assessment of blood pressure variability can be obtained only from the analysis of continuous, beat-by-beat, blood pressure recordings. Some information, however, can also be derived from analysis of discontinuous blood pressure tracings, such as those commonly performed in a clinical setting. This would require that attention is paid both to the quality of the recordings and to the selection of suitable analysis methods that should cope with the discontinuous nature of the measurements to be processed and to their intrinsic low sampling frequency.

High-altitude hypoxia and periodic breathing during sleep: gender-related differences.

High‐altitude exposure is characterized by the appearance of periodic breathing during sleep. Only limited evidence is available, however, on the presence of gender‐related differences in this breathing pattern. In 37 healthy subjects, 23 male and 14 female, we performed nocturnal cardio‐respiratory monitoring in the following conditions: (1) sea level; (2) first/second night at an altitude of 3400 m; (3) first/second night at an altitude of 5400 m and after a 10 day sojourn at 5400 m. At sea level, a normal breathing pattern was observed in all subjects throughout the night. At 3400 m the apnea–hypopnea index was 40.3 ± 33.0 in males (central apneas 77.6%, central hypopneas 22.4%) and 2.4 ± 2.8 in females (central apneas 58.2%, central hypopneas 41.8%; P < 0.01). During the first recording at 5400 m, the apnea–hypopnea index was 87.5 ± 35.7 in males (central apneas 60.0%, central hypopneas 40.0%) and 41.1 ± 44.0 in females (central apneas 73.2%, central hypopneas 26.8%; P < 0.01), again with a higher frequency of central events in males as seen at lower altitude. Similar results were observed after 10 days. With increasing altitude, there was also a progressive reduction in respiratory cycle length during central apneas in males (26.9 ± 3.4 s at 3400 m and 22.6 ± 3.7 s at 5400 m). Females, who displayed a significant number of central apneas only at the highest reached altitude, were characterized by longer cycle length than males at similar altitude (30.1 ± 5.8 s at 5400 m). In conclusion, at high altitude, nocturnal periodic breathing affects males more than females. Females started to present a significant number of central sleep apneas only at the highest reached altitude. After 10 days at 5400 m gender differences in the apnea–hypopnea index similar to those observed after acute exposure were still observed, accompanied by differences in respiratory cycle length.

Device-Guided Paced Breathing in the Home Setting Effects on Exercise Capacity, Pulmonary and Ventricular Function in Patients With Chronic Heart Failure: A Pilot Study

Background— Regular slow breathing is known to improve autonomic cardiac regulation and reduce chemoreflex sensitivity in heart failure. We explored the acceptability and usefulness of a device for paced slow breathing at the home setting. Methods and Results— In this open pilot study, 24 patients with chronic heart failure (61% males, mean age, 64±9 years; New York Heart Association class, 2.81±0.01) were randomized to a control group receiving conventional treatment (n=12) or to a group receiving conventional treatment and device-guided paced breathing (n=12). Groups were comparable for age, therapies, and clinical characteristics. They were evaluated at baseline and again after 10 weeks by Doppler echocardiography, pulmonary function, cardiopulmonary stress test, and quality of life (Minnesota Quality of Life questionnaire). The treatment group was instructed to use the equipment for 18 minutes twice daily. The device is a computerized box connected to a belt-type respiration sensor and to headphones; it generates musical tones (based on the user’s breathing rate and inspiration ratio), which guide the user to progressively and effortlessly slow his or her breathing rate <10 breaths/min. The treatment group showed high compliance to the device (90% of the prescribed sessions were completed). Blinded analysis of data demonstrated increased ejection fraction and decreased estimated pulmonary pressure in the echocardiograms of the treated group versus controls and favorable changes in New York Heart Association class, Ve/Vco2, FEV1, and a quality of life measure, as well (all P <0.05). Conclusions— This pilot investigation demonstrates that device-guided paced breathing at home is feasible and results in an improvement in clinically relevant parameters for patients with heart failure and systolic dysfunction. Received February 12, 2008; accepted July 23, 2008.Background—Regular slow breathing is known to improve autonomic cardiac regulation and reduce chemoreflex sensitivity in heart failure. We explored the acceptability and usefulness of a device for paced slow breathing at the home setting. Methods and Results—In this open pilot study, 24 patients with chronic heart failure (61% males, mean age, 64±9 years; New York Heart Association class, 2.81±0.01) were randomized to a control group receiving conventional treatment (n=12) or to a group receiving conventional treatment and device-guided paced breathing (n=12). Groups were comparable for age, therapies, and clinical characteristics. They were evaluated at baseline and again after 10 weeks by Doppler echocardiography, pulmonary function, cardiopulmonary stress test, and quality of life (Minnesota Quality of Life questionnaire). The treatment group was instructed to use the equipment for 18 minutes twice daily. The device is a computerized box connected to a belt-type respiration sensor and to headphones; it generates musical tones (based on the user’s breathing rate and inspiration ratio), which guide the user to progressively and effortlessly slow his or her breathing rate <10 breaths/min. The treatment group showed high compliance to the device (90% of the prescribed sessions were completed). Blinded analysis of data demonstrated increased ejection fraction and decreased estimated pulmonary pressure in the echocardiograms of the treated group versus controls and favorable changes in New York Heart Association class, Ve/Vco2, FEV1, and a quality of life measure, as well (all P<0.05). Conclusions—This pilot investigation demonstrates that device-guided paced breathing at home is feasible and results in an improvement in clinically relevant parameters for patients with heart failure and systolic dysfunction.

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.

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.

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 β-blockers are known to affect exercise capacity in normoxia, no data are available comparing selective and nonselective β-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.

Device-Guided Paced Breathing in the Home SettingCLINICAL PERSPECTIVE

Background— Regular slow breathing is known to improve autonomic cardiac regulation and reduce chemoreflex sensitivity in heart failure. We explored the acceptability and usefulness of a device for paced slow breathing at the home setting. Methods and Results— In this open pilot study, 24 patients with chronic heart failure (61% males, mean age, 64±9 years; New York Heart Association class, 2.81±0.01) were randomized to a control group receiving conventional treatment (n=12) or to a group receiving conventional treatment and device-guided paced breathing (n=12). Groups were comparable for age, therapies, and clinical characteristics. They were evaluated at baseline and again after 10 weeks by Doppler echocardiography, pulmonary function, cardiopulmonary stress test, and quality of life (Minnesota Quality of Life questionnaire). The treatment group was instructed to use the equipment for 18 minutes twice daily. The device is a computerized box connected to a belt-type respiration sensor and to headphones; it generates musical tones (based on the user’s breathing rate and inspiration ratio), which guide the user to progressively and effortlessly slow his or her breathing rate <10 breaths/min. The treatment group showed high compliance to the device (90% of the prescribed sessions were completed). Blinded analysis of data demonstrated increased ejection fraction and decreased estimated pulmonary pressure in the echocardiograms of the treated group versus controls and favorable changes in New York Heart Association class, Ve/Vco2, FEV1, and a quality of life measure, as well (all P <0.05). Conclusions— This pilot investigation demonstrates that device-guided paced breathing at home is feasible and results in an improvement in clinically relevant parameters for patients with heart failure and systolic dysfunction. Received February 12, 2008; accepted July 23, 2008.Background—Regular slow breathing is known to improve autonomic cardiac regulation and reduce chemoreflex sensitivity in heart failure. We explored the acceptability and usefulness of a device for paced slow breathing at the home setting. Methods and Results—In this open pilot study, 24 patients with chronic heart failure (61% males, mean age, 64±9 years; New York Heart Association class, 2.81±0.01) were randomized to a control group receiving conventional treatment (n=12) or to a group receiving conventional treatment and device-guided paced breathing (n=12). Groups were comparable for age, therapies, and clinical characteristics. They were evaluated at baseline and again after 10 weeks by Doppler echocardiography, pulmonary function, cardiopulmonary stress test, and quality of life (Minnesota Quality of Life questionnaire). The treatment group was instructed to use the equipment for 18 minutes twice daily. The device is a computerized box connected to a belt-type respiration sensor and to headphones; it generates musical tones (based on the user’s breathing rate and inspiration ratio), which guide the user to progressively and effortlessly slow his or her breathing rate <10 breaths/min. The treatment group showed high compliance to the device (90% of the prescribed sessions were completed). Blinded analysis of data demonstrated increased ejection fraction and decreased estimated pulmonary pressure in the echocardiograms of the treated group versus controls and favorable changes in New York Heart Association class, Ve/Vco2, FEV1, and a quality of life measure, as well (all P<0.05). Conclusions—This pilot investigation demonstrates that device-guided paced breathing at home is feasible and results in an improvement in clinically relevant parameters for patients with heart failure and systolic dysfunction.