Bayer HealthCare

Rationale and Objective

Exposure to high altitude is associated with important changes in cardiovascular regulation,^1,2 mainly due to hypoxia caused by a decreased oxygen partial pressure in the ambient air. Hypoxia, through stimulation of chemoreceptors, activates the sympathetic nervous system,^3,4 leading to an increase in heart rate (HR) and blood pressure (BP).^2,5-7

Because of the massive development of tourism and sport activities in mountain areas, millions of people are periodically exposed to altitudes above 2500 m. Although a substantial number of these people are likely to be affected by hypertension or cardiovascular problems, little is known about the BP responses to high altitude in hypertensive patients. Even less is known about the effects and tolerability of antihypertensive drugs in such conditions.²

Previous findings confirmed an acute pressor (BP-raising) effect of high altitude in lowlanders, which was partly counteracted by BP-lowering medications.⁷ However, it is not clear whether subjects with known hypertension at sea level will show a similar response. Also, little information is available regarding the choice of drugs effective in preventing an excessive BP increase at high altitude.

In a previous study, the ARB telmisartan was shown to maintain its BP-lowering efficacy in normotensive subjects at high altitude (1-3 days at 3500 m) [unpublished data]. The calcium channel-blocker nifedipine (mainly used in a slow-release GITS form) is also known to effectively lower pulmonary artery pressure, typically elevated at high altitude, and has been successfully applied in the treatment of high altitude pulmonary oedema. However, its effects on systemic BP at high altitude have not been systematically studied.

Results of the recent TALENT study showed that the combination of telmisartan 80 mg and nifedipine GITS 20 mg was more effective than either monotherapy when administered first-line in high risk hypertensive patients.⁸ Combination therapy was also associated with a good safety and tolerability profile.

The principal objectives of HIGHCARE-Andes are:

To assess the response of BP to high altitude exposure in hypertensive subjects who usually reside at sea level

To assess the efficacy and safety of the combination of telmisartan and nifedipine GITS in preventing excessive BP increase in hypertensive subjects exposed to high altitude

References

1. Hainsworth R, Drinkhill MJ. Cardiovascular adjustments for life at high altitude. Respir Physiol Neurobiol. 2007;158:204-11.
2. Mieske K, Flaherty G, O'Brien T. Journeys to high altitude – risks and recommendations for travelers with preexisting medical conditions. J Travel Med. 2010;17:48-62.
3. Duplain H, Vollenweider L, Delabays A, Nicod P, Bartsch P, Scherrer U. Augmented sympathetic activation during short-term hypoxia and high-altitude exposure in subjects susceptible to high-altitude pulmonary edema. Circulation. 1999;99:1713-18.
4. Hansen J, Sander M. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia. J Physiol. 2003;546:921-9.
5. Bärtsch P, Gibbs JS. Effect of altitude on the heart and the lungs. Circulation. 2007;116:2191-202.
6. Higgins JP, Tuttle T, Higgins JA. Altitude and the heart: is going high safe for your cardiac patient? Am Heart J. 2010;159:25-32.
7. Bilo G, Caldara G, Styczkiewicz K, Revera M, Lombardi C, Giglio A, Zambon A, Corrao G, Faini A, Valentini M, Mancia G, Parati G. Effects of selective and nonselective beta-blockade on 24-h ambulatory blood pressure under hypobaric hypoxia at altitude. J Hypertens. 2011;29:380-7.
8. Mancia G, Parati G, Bilo G, Choi J, Ochan Kilama M, Ruilope LM, on behalf of the TALENT investigators. Blood pressure control by the nifedipine GITS–telmisartan combination in patients at high cardiovascular risk: the TALENT study. J Hypertens. 2011;29:600-9.