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.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830530.

Keywords: blood pressure; exercise physiology; high altitude; hypoxia; oxygen consumption.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1

Multipoint relationship between systolic blood pressure and oxygen consumption in 2 exemplificative cases randomized to active treatment (white) and to placebo (black), exercising both at sea level (circles) and at altitude (triangles). HA indicates high altitude; SBP, systolic blood pressure; SL, sea level; T/N‐GITS, telmisartan 80 mg/nifedipine‐GITS 30 mg; VO 2, oxygen consumption.

Figure 2

Systolic blood pressure as a function of oxygen consumption during exercise in the different study settings and according to treatment group. In this exemplificative figure, mean slopes for each treatment group in each study condition are plotted, with the relative intercepts. Continuous lines represent the blood pressure response in a physiological range of VO 2 values during exercise. Dashed lines represent extrapolation until the systolic blood pressure intercept on the y‐axis. HA indicates high altitude; SBP, systolic blood pressure; SL, sea level; T/N‐GITS, telmisartan 80 mg/nifedipine‐GITS 30 mg; VO 2, oxygen consumption.

Figure 3

Relationship between oxygen consumption and workload in the 2 treatment groups. Continuous lines represent the mean slope value for each treatment group in a physiological range of workload. Dashed lines represent extrapolation until the oxygen consumption intercept on the y‐axis. T/N‐GITS indicates telmisartan 80 mg/nifedipine‐GITS 30 mg; VO 2, oxygen consumption.