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

Valentini, Mariaconsuelo; Revera, Miriam; Bilo, Grzegorz; Caldara, G; Savia, Giulio; Styczkiewicz, Katarzyna; Parati, S.; Gregorini, Francesca; Faini, Andrea; Branzi, Giovanna; Malfatto, Gabriella; Magrì, Damiano; Agostoni, Piergiuseppe; Parati, Gianfranco

doi:10.1111/j.1755-5922.2011.00261.x

Cited by 33 publications

(23 citation statements)

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“…Of note, the reduced exercise performance during HA exposure, similar to what has been shown in HF patients, may be favorably modulated by selective beta1-blockers such as bisoprolol and nebivolol (Valentini et al, 2012;Agostoni, 2013).…”

Section: Effects Of Aging On Blood Pressure and Its Regulation At Higmentioning

confidence: 81%

“…Hypoxia is a potent sympathetic activator via stimulation of the peripheral chemoreceptors, as demonstrated by the increase in heart rate and plasma norepinephrine observed in this condition (Wolfel et al, 1994). Similarly, in the placebo group of HIGHCAREHimalaya study, noradrenaline showed a marked progressive increase with exposure to the 3400 and 5400 m altitudes, with a tendency to return to baseline values upon return to sea level (Valentini et al, 2012;Agostoni et al, 2013;Parati et al, 2014a) (Fig. 5).…”

Section: Physiological Mechanisms Underlying Bp Responses To High Altmentioning

confidence: 88%

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Aging, High Altitude, and Blood Pressure: A Complex Relationship

Parati

Ochoa

Torlasco

et al. 2015

High Altitude Medicine & Biology

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Parati, Gianfranco, Juan Eugenio Ochoa, Camilla Torlasco, Paolo Salvi, Carolina Lombardi, and Grzegorz Bilo. Aging, high altitude, and blood pressure: A complex relationship. High Alt Biol Med 16:97-109, 2015.--Both aging and high altitude exposure may induce important changes in BP regulation, leading to significant increases in BP levels. By inducing atherosclerotic changes, stiffening of large arteries, renal dysfunction, and arterial baroreflex impairment, advancing age may induce progressive increases in systolic BP levels, promoting development and progression of arterial hypertension. It is also known, although mainly from studies in young or middle-aged subjects, that exposure to high altitude may influence different mechanisms involved in BP regulation (i.e., neural central and reflex control of sympathetic activity), leading to important increases in BP levels. The evidence is less clear, however, on whether and to what extent advancing age may influence the BP response to acute or chronic high altitude exposure. This is a question not only of scientific interest but also of practical relevance given the consistent number of elderly individuals who are exposed for short time periods (either for leisure or work) or live permanently at high altitude, in whom arterial hypertension is frequently observed. This article will review the evidence available on the relationship between aging and blood pressure levels at high altitude, the pathophysiological mechanisms behind this complex association, as well as some questions of practical interest regarding antihypertensive treatment in elderly subjects, and the effects of antihypertensive drugs on blood pressure response during high altitude exposure.

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Section: Effects Of Aging On Blood Pressure and Its Regulation At Higmentioning

confidence: 81%

Section: Physiological Mechanisms Underlying Bp Responses To High Altmentioning

confidence: 88%

Aging, High Altitude, and Blood Pressure: A Complex Relationship

Parati

Ochoa

Torlasco

et al. 2015

High Altitude Medicine & Biology

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“…This did not translate into improved exercise capacity; however, it did not result in any adverse effect nor in a reduction of physical performance. This is at variance from other antihypertensive drugs suggested to be used at altitude, such as some beta blockers, that may have a negative impact on ventilatory control and exercise capacity in hypoxic conditions 25, 26, 27. Moreover, the slope of the VO 2 /work relationship was unaffected by high altitude (3260 m) both in the active treatment group and in the placebo group, suggesting that during effort, compensatory mechanisms allow oxygen delivery to muscles to remain stable.…”

Section: Discussionmentioning

confidence: 99%

Upward Shift and Steepening of the Blood Pressure Response to Exercise in Hypertensive Subjects at High Altitude

Caravita

Faini

Baratto

et al. 2018

JAHA

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BackgroundAcute exposure to high‐altitude hypobaric hypoxia induces a blood pressure rise in hypertensive humans, both at rest and during exercise. It is unclear whether this phenomenon reflects specific blood pressure hyperreactivity or rather an upward shift of blood pressure levels. We aimed at evaluating the extent and rate of blood pressure rise during exercise in hypertensive subjects acutely exposed to high altitude, and how these alterations can be counterbalanced by antihypertensive treatment.Methods and ResultsFifty‐five subjects with mild hypertension, double‐blindly randomized to placebo or to a fixed‐dose combination of an angiotensin‐receptor blocker (telmisartan 80 mg) and a calcium‐channel blocker (nifedipine slow release 30 mg), performed a cardiopulmonary exercise test at sea level and after the first night's stay at 3260 m altitude. High‐altitude exposure caused both an 8 mm Hg upward shift (P<0.01) and a 0.4 mm Hg/mL/kg per minute steepening (P<0.05) of the systolic blood pressure/oxygen consumption relationship during exercise, independent of treatment. Telmisartan/nifedipine did not modify blood pressure reactivity to exercise (blood pressure/oxygen consumption slope), but downward shifted (P<0.001) the relationship between systolic blood pressure and oxygen consumption by 26 mm Hg, both at sea level and at altitude. Muscle oxygen delivery was not influenced by altitude exposure but was higher on telmisartan/nifedipine than on placebo (P<0.01).ConclusionsIn hypertensive subjects exposed to high altitude, we observed a hypoxia‐driven upward shift and steepening of the blood pressure response to exercise. The effect of the combination of telmisartan/nifedipine slow release outweighed these changes and was associated with better muscle oxygen delivery.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830530.

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“…Differently, it is now appreciated that the exercise performance of healthy subjects at high altitude is influenced by the type of b-blocker used. In a recent report, Valentini et al (2011) showed that at Capanna Regina Margherita (4560 m) peak Vo 2 was lower in healthy subjects treated with carvedilol (b 1 -b 2 receptor blocker) than in those on nebivolol (a selective b 1 receptor blocker). This difference was related to a greater peak exercise ventilation at altitude with nebivolol versus carvedilol.…”

Section: Introductionmentioning

confidence: 96%

Considerations on Safety and Treatment of Patients with Chronic Heart Failure at High Altitude

Agostoni

2013

High Altitude Medicine & Biology

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Prognosis and quality of life of chronic heart failure (HF) patients have greatly improved over the last decade. Consequently, many patients are willing to spend leisure time at altitude, usually <3500 m, but their safety in doing so is undefined. HF is a syndrome that often has relevant co-morbidities, such as pulmonary hypertension, COPD, unstable cardiac ischemia, and anemia. HF co-morbidities may per se impede a safe stay at altitude. Exercise at simulated altitude is associated with a reduction in performance, which is greater in HF patients than in normal subjects and greater in patients with most severe HF. In normal subjects, the reduction in performance is ∼2% every 1000 m altitude increase, whereas it is 4% and 10% in HF patients with normal or slightly diminished exercise capacity and in HF patients with markedly diminished exercise capacity. On-field experience with HF patients at altitude is limited to subjects driven to altitude (3454 m) for a few hours. The data showed a reduction in exercise capacity similar to that reported at simulated altitude. "Optimal" HF treatment in patients spending time at altitude is likely different from optimal treatment at sea level, particularly as regards β-blockers. Carvedilol, a β1-β2-α-blocker, reduces the hypoxic ventilatory response through a reduction of the chemoreflex response, and it reduces alveolar-capillary gas diffusion, which is under control by β2-receptors. These actions are not shared by selective β1-blockers such as bisoprolol and nebivolol, which should be preferred for treatment of HF patients willing to spend time at altitude. In conclusion, spending time at altitude (<3500 m) is safe for HF patients, provided that subjects are free of co-morbidities that may directly interfere with the adaptation to altitude. However, HF patients experience a reduction of exercise capacity in proportion to HF severity and altitude. Finally, HF patients should undergo a specific "altitude-tailored treatment" to avoid pharmacological interference with altitude adaptation mechanisms.

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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

Cited by 33 publications

References 40 publications

Aging, High Altitude, and Blood Pressure: A Complex Relationship

Aging, High Altitude, and Blood Pressure: A Complex Relationship

Upward Shift and Steepening of the Blood Pressure Response to Exercise in Hypertensive Subjects at High Altitude

Considerations on Safety and Treatment of Patients with Chronic Heart Failure at High Altitude

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