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

Abstract

Background--Acute 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 Results--Fifty-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).Conclusions--In 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. In previous articles, we demonstrated that acute exposure to high-altitude hypobaric hypoxia induces a blood pressure (BP) rise in subjects with hypertension, both at rest over the 24 hours and during exercise, 1-3 likely through chemoreflex-induced sympathetic activation.4-6 Moreover, we also showed that the combination treatment with telmisartan and sustained-release formulation of nifedipine gastrointestinal therapeutic system formulation (GITS) is able to lower BP levels during exercise not only at sea level but also at high altitude, as compared with placebo. However, we previously Indeed, it is a common experience that a given task (eg, climbing stairs, which may correspond to a given workload) may engender extremely different responses in terms of dyspnea, fatigue, or palpitations when conducted either at sea level or at high altitude. For these reasons, in a previous report of ours, we also tried to normalize BP for oxygen consumption (VO 2 ), the latter being acknowledged as a more precise indicator of cardiac output and metabolic needs imposed by exercise than is the measure of workload. However, we assessed this ratio only at peak exercise and not dynamically throughout the different exercise steps. Thus, it remains debated whe...