Ambulatory Blood Pressure in Untreated and Treated Hypertensive Patients at High Altitude

Abstract

A cute exposure to high-altitude hypoxia induces important changes in cardiovascular regulation, [1][2][3][4] including an increase in blood pressure (BP) and heart rate (HR). 2,[5][6][7][8] Millions of subjects travel for relatively short periods of time to high altitude either for work or for leisure including many affected by hypertension 9 in whom the pressor effect of high altitude may be relevant. Limited information is available, however, on the acute BP effects of high altitude in hypertensive subjects, 10 and on the effectiveness and tolerability of antihypertensive drugs under these circumstances. As a result, the few recommendations published on the management of hypertensive subjects planning to spend time at high altitude for either leisure or work are largely based on experts' opinion rather than on evidence. 2,[11][12][13][14] Both angiotensin receptor blockers (ARBs) and dihydropyridine calcium antagonists are widely used for the monotherapy of hypertension, and their combination has been included among the preferred therapeutic choices by recent Abstract-Blood pressure increases during acute exposure to high altitude in healthy humans. However, little is known on altitude effects in hypertensive subjects or on the treatment efficacy in this condition. Objectives of High Altitude Cardiovascular Research (HIGHCARE)-Andes Lowlanders Study were to investigate the effects of acute high-altitude exposure on 24-hour ambulatory blood pressure in hypertensive subjects and to assess antihypertensive treatment efficacy in this setting. One hundred untreated subjects with mild hypertension (screening blood pressure, 144.1±9.8 mm Hg systolic, 92.0±7.5 mm Hg diastolic) were randomized to double-blind placebo or to telmisartan 80 mg+modified release nifedipine 30 mg combination. Twenty-four-hour ambulatory blood pressure monitoring was performed off-treatment, after 6 weeks of treatment at sea level, on treatment during acute exposure to high altitude (3260 m) and immediately after return to sea level. Eighty-nine patients completed the study (age, 56.4±17.6 years; 52 men/37 women; body mass index, 28.2±3.5 kg/ m 2 ). Twenty-four-hour systolic blood pressure increased at high altitude in both groups (placebo, 11.0±9 mm Hg; P<0.001 and active treatment, 8.1±10.4 mm Hg; P<0.001). Active treatment reduced 24-hour systolic blood pressure both at sea level and at high altitude (147.9±11.1 versus 132.6±12.4 mm Hg for placebo versus treated; P<0.001; 95% confidence interval of the difference 10.9-19.9 mm Hg) and was well tolerated. Similar results were obtained for diastolic, for daytime blood pressure, and for nighttime blood pressure. Treatment was well tolerated in all conditions. Our study demonstrates that (1) 24-hour blood pressure increases significantly during acute high-altitude exposure in hypertensive subjects and (2) treatment with angiotensin receptor blocker-calcium channel blocker combination is effective and safe in this condition. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique...

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

“…Moreover, it is unclear whether antihypertensive therapy would just result in a downward shift of BP levels, or if it might also reduce the rate of BP increase occurring during exercise, thus modulating BP hyperreactivity. These questions were not addressed in our previous article,1, 2, 3 and discordant answers were found on the basis of the results of the few studies that addressed these issues up to now 7, 8, 9…”

“…One hundred individuals with grade I essential hypertension (conventional systolic BP 140–159 mm Hg or conventional diastolic BP 90–99 mm Hg and mean daytime systolic BP ≥135 and <150 mm Hg and/or mean daytime diastolic BP ≥85 and <95 mm Hg) and no significant comorbidities, either untreated or having previously stopped antihypertensive therapy for 4 weeks, were enrolled in the frame of the HIGHCARE‐ANDES study 1. All subjects were sea‐level residents.…”

“…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, 2, 3 likely through chemoreflex‐induced sympathetic activation 4, 5, 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.…”

Renin–Angiotensin–Aldosterone System Is Not Involved in the Arterial Stiffening Induced by Acute and Prolonged Exposure to High Altitude

“…24 We have previously shown that during short exposure to lower altitudes (≈3400 m) when RAAS at least partly retains its activity, the angiotensin antagonist telmisartan remains effective in BP lowering both in normotensive 24 and in hypertensive subjects. 41 Conversely, telmisartan lost its ability to reduce BP during prolonged exposure to very HA, likely because of the above reported suppression of RAAS. 24 In line with these findings, we also observed no difference in parameters reflecting viscoelastic properties of large arteries, such as PWV and other variables obtained from pulse wave analysis, including subendocardial oxygen supply and demand ratio, between telmisartan-treated and untreated subjects at any altitude.…”

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

“…In the HIGHCARE-Andes Lowlanders Study, BP changes in response to high altitude exposure and the BP effects of antihypertensive combination treatment with an angiotensin II receptor blocker and a calcium channel blocker (ARB/ CCB) both at sea level and during high altitude exposure were assessed in a group of patients with mild hypertension (Bilo et al, 2015).…”