Milan, Italy – Results of the HIGHCARE 2008 Project were announced during the 19th Scientific Meeting of the European Society of Hypertension by Prof. Gianfranco Parati, MD (Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Italy), the chairman and lead investigator of the project. The first-ever ambulatory blood pressure (ABPM) study, said Parati, “conducted at high and very high altitude investigated treatment with telmisartan” showed that:
- in conditions of hypobaric hypoxia (oxygen deficiency), 24-hour BP increased in a sustained manner proportional to the altitude reached;
- the effects of hypobaric hypoxia at high altitude are similar to the effects of reduced oxygen availability observed in diseases associated with respiratory disorders, such as chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), arterial hypertension related to sleep apnea syndrome and/or severe obesity. Together, these diseases affect more than 600 million people worldwide giving the study results great significance;
- treatment with telmisartan, an angiotensin II receptor blocker, reduces BP compared with placebo at high altitude, up to at least 3500 m above sea level, demonstrating potential control of hypoxia-induced BP alterations;
- at very high altitude, 5400 m above sea level, BP effects between the telmisartan and placebo groups was comparable, consistent with changes in the functioning of the renin-angiotensin-aldosterone system (RAAS).
Physiological changes occurring at high altitude are mainly due to decreased atmospheric pressure leading to hypoxia and hypoxemia.
People with sleep apnea syndrome develop high BP in response to hypoxia, a lack of oxygen in their blood. In the HIGHCARE 2008 project, this condition has been simulated by hypobaric hypoxia, often associated with sleep-related breathing disorders, which occurs at high altitude. We found that telmisartan, the antihypertensive drug we tested, was able to control this effect at altitudes of up to 3500 m, at which the lack of oxygen is similar to the degree of hypoxemia most commonly experienced by sleep apnea sufferers, the investigators said.
The randomised, parallel group, double-blind, placebo-controlled trial with telmisartan 80 mg was conducted in 38 healthy subjects with a moderate level of physical fitness. The effects of telmisartan on 24-hour ambulatory BP were measured under acute and prolonged exposure to high altitude hypoxia. Key results showed that following treatment with telmisartan for 6 weeks at sea level and also following acute exposure to high altitude (3500 m):
- 24-hour SBP/DBP at sea level were significantly reduced with telmisartan compared with placebo (SBP: 112.07.8 vs. 116.48.6, p = 0.0025; DBP: 69.05.8 vs. 74.05.8, p = 0.002)
- 24-hour SBP/DBP at 3500 m were also significantly reduced with telmisartan compared with placebo (SBP: 120.09.7 vs. 125.08.7,p = 0.0056; DBP: 75.76.5 vs. 81.15.7, p = 0.009)
- at very high altitude, 5400 m, 24-hour SBP/DBP was comparable between the telmisartan and placebo groups (SBP: 130.111.1 vs. 130.711.2, p = NS; DBP: 82.17.1 vs. 84.26.6, p = NS), consistent with changes in functioning of the RAAS.
These changes may explain why a treatment that works on the RAAS may not provide benefits at very high altitude, said the researchers.
The RAAS is involved in the occurrence of a number of cardiovascular (CV) conditions, including hypertension and heart failure. Therapeutic agents acting on the RAAS, including angiotensin II receptor blockers such as telmisartan, have beneficial CV effects.
Grzegorz Bilo, MD (Istituto Auxologico Italiano and Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Italy), commented: “When moving to an even higher altitude, and thus further increasing the hypoxia above the levels often experienced in sleep apnea, the blockade of the RAAS was no longer able to control the hypoxia-induced blood pressure increase”. This suggests that other mechanisms were involved and could explain the blood pressure changes observed. Even though this is an artificial setting, “the data we have collected will provide important insights into the physiological and molecular basis of hypoxia induced hypertension,” said Bilo.
Prof. Parati concluded: “While the data that we have collected needs to be confirmed by further studies, what we can take away from this expedition is that although Everest is one of the most hostile places on earth, it might actually help us save lives by giving us a better understanding of the changes induced by hypoxia in the human body.”