Andrea Faini

Relationship Between Short-Term Blood Pressure Variability and Large-Artery Stiffness in Human Hypertension: Findings From 2 Large Databases

Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hypertensive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP, r=0.17/0.19/0.13; weighted SD of 24-hour SBP, r=0.21; ARV, r=0.26; all P<0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all P<0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD.

Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project

Iron is tightly connected to oxygen homeostasis and erythropoiesis. Our aim was to better understand how hypoxia regulates iron acquisition for erythropoiesis in humans, a topic relevant to common hypoxia-related disorders. Forty-seven healthy volunteers participated in the HIGHCARE project. Blood samples were collected at sea level and after acute and chronic exposure to high altitude (3400-5400 m above sea level). We investigated the modifications in hematocrit, serum iron indices, erythropoietin, markers of erythropoietic activity, interleukin-6, and serum hepcidin. Hepcidin decreased within 40 hours after acute hypoxia exposure (P < .05) at 3400 m, reaching the lowest level at 5400 m (80% reduction). Erythropoietin significantly increased (P < .001) within 16 hours after hypoxia exposure followed by a marked erythropoietic response supported by the increased iron supply. Growth differentiation factor-15 progressively increased during the study period. Serum ferritin showed a very rapid decrease, suggesting the existence of hypoxia-dependent mechanism(s) regulating storage iron mobilization. The strong correlation between serum ferritin and hepcidin at each point during the study indicates that iron itself or the kinetics of iron use in response to hypoxia may signal hepcidin down-regulation. The combined and significant changes in other variables probably contribute to the suppression of hepcidin in this setting.

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.

Effects of acetazolamide on central blood pressure, peripheral blood pressure, and arterial distensibility at acute high altitude exposure

AIMS We assessed the haemodynamic changes induced by exposure to high altitude hypoxia and the effects on them of acetazolamide, a drug prescribed to prevent and treat mountain sickness. METHODS AND RESULTS In 42 subjects (21 males, age 36.8 ± 8.9 years) randomized to double blind acetazolamide 250 mg b.i.d. or placebo, pulse wave velocity and pulse wave parameters were assessed (PulsePen) at baseline; after 2-day treatment at sea level; within 6 h and on 3rd day of exposure to high altitude. Exposure to high altitude significantly increased diastolic (P < 0.005) and mean blood pressure (BP) (P < 0.05, after prolonged exposure) in placebo but not in the acetazolamide group. Therefore, subjects on acetazolamide showed significantly lower values of diastolic (P < 0.005) and mean BP (P < 0.05) at altitude. Furthermore, they also showed significantly lower values of systolic BP (P < 0.05). Pulse wave velocity did not change at high altitude, while the augmentation index, normalized for a theoretical heart rate of 75 b.p.m., significantly increased (P < 0.05) under placebo, but not under acetazolamide. In a multivariate model, unadjusted augmentation index at high altitude was not affected by BP changes, while significant determinants were heart rate and gender. CONCLUSION Acute exposure to high altitude induced a rise in brachial BP and changes in pulse waveform-derived parameters, independent from changes in mean BP and partly counteracted by treatment with acetazolamide. The impact of acetazolamide on the haemodynamic alterations induced by hypobaric hypoxia may be considered among the beneficial effects of this drug in subjects prone to mountain sickness. CLINICAL TRIAL REGISTRATION EudraCT Number: 2010-019986-27.

A wearable system for the seismocardiogram assessment in daily life conditions

Seismocardiogram (SCG) is the recording of the minute body accelerations induced by the heart activity, and reflects mechanical aspects of heart contraction and blood ejection. So far, most of the available systems for the SCG assessment are designed to be used in a laboratory or in controlled behavioral and environmental conditions. In this paper we propose a modified version of a textile-based wearable device for the unobtrusive recording of ECG, respiration and accelerometric data (the MagIC system), to assess the 3d sternal SCG in daily life. SCG is characterized by an extremely low magnitude of the accelerations (in the order of g × 10−3), and is masked by major body accelerations induced by locomotion. Thus in daily life recordings, SCG can be measured whenever the subject is still. We observed that about 30 seconds of motionless behavior are sufficient for a stable estimate of the average SCG waveform, independently from the subjects posture. Since it is likely that during spontaneous behavior the subject may stay still for at least 30 seconds several times in a day, it is expected that the SCG could be repeatedly estimated and tracked over time through a prolonged data recording. These observations represent the first testing of the system in the assessment of SCG out of a laboratory environment, and open the possibility to perform SCG studies in a wide range of everyday conditions without interfering with the subjects activity tasks.

A New Solar-Powered Blood Pressure Measuring Device for Low-Resource Settings

The management of high blood pressure (BP) is particularly inadequate in low-income countries, where the unavailability of a reliable, durable, and affordable BP-measurement device is a major obstacle to accurate diagnosis. Recognizing this, a World Health Organization committee was established to correct this deficiency by influencing manufacturers to produce a device according to predetermined criteria and to demonstrate the suitability of the device for low resource settings. A device, which fulfilled stipulated criteria in being inexpensive, semiautomated, and solar powered, was validated according to the International Protocol of the European Society of Hypertension; it was then subjected to field testing in 716 subjects from 2 centers in Uganda and 1 in Zambia. The Omron HEM-SOLAR having previously fulfilled accuracy criteria of the International Protocol for both systolic blood pressure (SBP) and diastolic blood pressure (DBP), fulfilled criteria for SBP, but not for DBP, when revalidated. In field testing, average SBPs and DBPs were 120.5±21.6/74.6±13.8 mm Hg and 122.3±21.8/71.2±14.0 mm Hg, respectively, with the auscultatory technique and the Omron HEM-SOLAR, respectively. Between-device agreement in defining SBP was 93.7%. The Omron HEM-SOLAR was favored over the mercury sphygmomanometer by both patients and investigators. In summary, considering the accuracy, robustness, relatively low cost, operational simplicity, and advantages such as solar power, the Omron HEM-SOLAR is likely to be a valuable device for improving BP measurement in low-resource settings with nonphysician health workers.

High-altitude exposure of three weeks duration increases lung diffusing capacity in humans

BACKGROUND high-altitude adaptation leads to progressive increase in arterial Pa(O2). In addition to increased ventilation, better arterial oxygenation may reflect improvements in lung gas exchange. Previous investigations reveal alterations at the alveolar-capillary barrier indicative of decreased resistance to gas exchange with prolonged hypoxia adaptation, but how quickly this occurs is unknown. Carbon monoxide lung diffusing capacity and its major determinants, hemoglobin, alveolar volume, pulmonary capillary blood volume, and alveolar-capillary membrane diffusion, have never been examined with early high-altitude adaptation. METHODS AND RESULTS lung diffusion was measured in 33 healthy lowlanders at sea level (Milan, Italy) and at Mount Everest South Base Camp (5,400 m) after a 9-day trek and 2-wk residence at 5,400 m. Measurements were adjusted for hemoglobin and inspired oxygen. Subjects with mountain sickness were excluded. After 2 wk at 5,400 m, hemoglobin oxygen saturation increased from 77.2 ± 6.0 to 85.3 ± 3.6%. Compared with sea level, there were increases in hemoglobin, lung diffusing capacity, membrane diffusion, and alveolar volume from 14.2 ± 1.2 to 17.2 ± 1.8 g/dl (P < 0.01), from 23.6 ± 4.4 to 25.1 ± 5.3 ml·min(-1)·mmHg(-1) (P < 0.0303), 63 ± 34 to 102 ± 65 ml·min(-1)·mmHg(-1) (P < 0.01), and 5.6 ± 1.0 to 6.3 ± 1.1 liters (P < 0.01), respectively. Pulmonary capillary blood volume was unchanged. Membrane diffusion normalized for alveolar volume was 10.9 ± 5.2 at sea level rising to 16.0 ± 9.2 ml·min(-1)·mmHg(-1)·l(-1) (P < 0.01) at 5,400 m. CONCLUSIONS at high altitude, lung diffusing capacity improves with acclimatization due to increases of hemoglobin, alveolar volume, and membrane diffusion. Reduction in alveolar-capillary barrier resistance is possibly mediated by an increase of sympathetic tone and can develop in 3 wk.

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.

Ambulatory Blood Pressure in Untreated and Treated Hypertensive Patients at High Altitude: The High Altitude Cardiovascular Research–Andes Study

Blood pressure increases during acute exposure to high altitude in healthy humans. However, little is known on altitude effects in hypertensive subjects or on the treatment efficacy in this condition. Objectives of High Altitude Cardiovascular Research (HIGHCARE)–Andes Lowlanders Study were to investigate the effects of acute high-altitude exposure on 24-hour ambulatory blood pressure in hypertensive subjects and to assess antihypertensive treatment efficacy in this setting. One hundred untreated subjects with mild hypertension (screening blood pressure, 144.1±9.8 mm Hg systolic, 92.0±7.5 mm Hg diastolic) were randomized to double-blind placebo or to telmisartan 80 mg+modified release nifedipine 30 mg combination. Twenty-four–hour ambulatory blood pressure monitoring was performed off-treatment, after 6 weeks of treatment at sea level, on treatment during acute exposure to high altitude (3260 m) and immediately after return to sea level. Eighty-nine patients completed the study (age, 56.4±17.6 years; 52 men/37 women; body mass index, 28.2±3.5 kg/m2). Twenty-four–hour systolic blood pressure increased at high altitude in both groups (placebo, 11.0±9 mm Hg; P <0.001 and active treatment, 8.1±10.4 mm Hg; P <0.001). Active treatment reduced 24-hour systolic blood pressure both at sea level and at high altitude (147.9±11.1 versus 132.6±12.4 mm Hg for placebo versus treated; P <0.001; 95% confidence interval of the difference 10.9–19.9 mm Hg) and was well tolerated. Similar results were obtained for diastolic, for daytime blood pressure, and for nighttime blood pressure. Treatment was well tolerated in all conditions. Our study demonstrates that (1) 24-hour blood pressure increases significantly during acute high-altitude exposure in hypertensive subjects and (2) treatment with angiotensin receptor blocker-calcium channel blocker combination is effective and safe in this condition. Clinical Trial Registration— URL: . Unique identifier: [NCT01830530][1]. # Novelty and Significance {#article-title-38} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01830530&atom=%2Fhypertensionaha%2F65%2F6%2F1266.atomBlood pressure increases during acute exposure to high altitude in healthy humans. However, little is known on altitude effects in hypertensive subjects or on the treatment efficacy in this condition. Objectives of High Altitude Cardiovascular Research (HIGHCARE)–Andes Lowlanders Study were to investigate the effects of acute high-altitude exposure on 24-hour ambulatory blood pressure in hypertensive subjects and to assess antihypertensive treatment efficacy in this setting. One hundred untreated subjects with mild hypertension (screening blood pressure, 144.1±9.8 mm Hg systolic, 92.0±7.5 mm Hg diastolic) were randomized to double-blind placebo or to telmisartan 80 mg+modified release nifedipine 30 mg combination. Twenty-four–hour ambulatory blood pressure monitoring was performed off-treatment, after 6 weeks of treatment at sea level, on treatment during acute exposure to high altitude (3260 m) and immediately after return to sea level. Eighty-nine patients completed the study (age, 56.4±17.6 years; 52 men/37 women; body mass index, 28.2±3.5 kg/m2). Twenty-four–hour systolic blood pressure increased at high altitude in both groups (placebo, 11.0±9 mm Hg; P<0.001 and active treatment, 8.1±10.4 mm Hg; P<0.001). Active treatment reduced 24-hour systolic blood pressure both at sea level and at high altitude (147.9±11.1 versus 132.6±12.4 mm Hg for placebo versus treated; P<0.001; 95% confidence interval of the difference 10.9–19.9 mm Hg) and was well tolerated. Similar results were obtained for diastolic, for daytime blood pressure, and for nighttime blood pressure. Treatment was well tolerated in all conditions. Our study demonstrates that (1) 24-hour blood pressure increases significantly during acute high-altitude exposure in hypertensive subjects and (2) treatment with angiotensin receptor blocker-calcium channel blocker combination is effective and safe in this condition. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830530.