Gianfranco Parati1, Grzegorz Bilo2, Andrea Faini2, Barbara Bilo2, Miriam Revera2, Andrea Giuliano3, Carolina Lombardi2, Gianluca Caldara2, Francesca Gregorini2, Katarzyna Styczkiewicz4, Antonella Zambon5, Alberto Piperno6, Pietro Amedeo Modesti7, Piergiuseppe Agostoni8, Giuseppe Mancia9. 1. Department of Health Sciences, University of Milano-Bicocca, Milan, Italy Department of Cardiovascular Neural and Metabolic Sciences, S.Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy gianfranco.parati@unimib.it. 2. Department of Cardiovascular Neural and Metabolic Sciences, S.Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy. 3. Department of Health Sciences, University of Milano-Bicocca, Milan, Italy Department of Cardiovascular Neural and Metabolic Sciences, S.Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy. 4. I Department of Cardiology and Hypertension, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. 5. Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy. 6. Department of Health Sciences, University of Milano-Bicocca, Milan, Italy. 7. Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy. 8. Centro Cardiologico Monzino, IRCCS, Milan, Italy Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. 9. Università di Milano-Bicocca, Milan, Italy IRCCS, Center of Epidemiology and Clinical Trials, Istituto Auxologico Italiano, Milan, Italy.
Abstract
AIM: Many hypertensive subjects travel to high altitudes, but little is known on ambulatory blood pressure (ABP) changes and antihypertensive drugs' efficacy under acute and prolonged exposure to hypobaric hypoxia. In particular, the efficacy of angiotensin receptor blockers in this condition is unknown. This may be clinically relevant considering that renin-angiotensin system activity changes at altitude. The HIGHCARE-HIMALAYA study assessed changes in 24 h ABP under acute and prolonged exposure to increasing altitude and blood pressure-lowering efficacy and safety of an angiotensin receptor blockade in this setting. METHODS AND RESULTS:Forty-seven healthy, normotensive lowlanders were randomized to telmisartan 80 mg or placebo in a double-blind, parallel group trial. Conventional and Ambulatory BPs were measured at baseline and on treatment: after 8 weeks at sea level, and under acute exposure to 3400 and 5400 m altitude, the latter upon arrival and after 12 days (Mt. Everest base camp). Blood samples were collected for plasma catecholamines, renin, angiotensin, and aldosterone. In both groups, exposure to increasing altitude was associated with: (i) significant progressive increases in conventional and 24 h blood pressure, persisting throughout the exposure to 5400 m; (ii) increased plasma noradrenaline and suppressed renin-angiotensin-aldosterone system. Telmisartan lowered 24 h ABP at the sea level and at 3400 m (between-group difference 4.0 mmHg, 95% CI: 2.2-9.5 mmHg), but not at 5400 m. CONCLUSION: Ambulatory blood pressure increases progressively with increasing altitude, remaining elevated after 3 weeks. An angiotensin receptor blockade maintains blood pressure-lowering efficacy at 3400 m but not at 5400 m. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIM: Many hypertensive subjects travel to high altitudes, but little is known on ambulatory blood pressure (ABP) changes and antihypertensive drugs' efficacy under acute and prolonged exposure to hypobaric hypoxia. In particular, the efficacy of angiotensin receptor blockers in this condition is unknown. This may be clinically relevant considering that renin-angiotensin system activity changes at altitude. The HIGHCARE-HIMALAYA study assessed changes in 24 h ABP under acute and prolonged exposure to increasing altitude and blood pressure-lowering efficacy and safety of an angiotensin receptor blockade in this setting. METHODS AND RESULTS: Forty-seven healthy, normotensive lowlanders were randomized to telmisartan 80 mg or placebo in a double-blind, parallel group trial. Conventional and Ambulatory BPs were measured at baseline and on treatment: after 8 weeks at sea level, and under acute exposure to 3400 and 5400 m altitude, the latter upon arrival and after 12 days (Mt. Everest base camp). Blood samples were collected for plasma catecholamines, renin, angiotensin, and aldosterone. In both groups, exposure to increasing altitude was associated with: (i) significant progressive increases in conventional and 24 h blood pressure, persisting throughout the exposure to 5400 m; (ii) increased plasma noradrenaline and suppressed renin-angiotensin-aldosterone system. Telmisartan lowered 24 h ABP at the sea level and at 3400 m (between-group difference 4.0 mmHg, 95% CI: 2.2-9.5 mmHg), but not at 5400 m. CONCLUSION: Ambulatory blood pressure increases progressively with increasing altitude, remaining elevated after 3 weeks. An angiotensin receptor blockade maintains blood pressure-lowering efficacy at 3400 m but not at 5400 m. Published on behalf of the European Society of Cardiology. All rights reserved.
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