HIGHCARE-ANDES 2012

ANDES

HIGH altitude Cardiovascular REsearch in the ANDES (HIGHCARE-ANDES) project is a compound of two distinct studies aimed at an improvement in the understanding of cardiovascular physiology and pathophysiology in the conditions of high altitude hypobaric hypoxia, with a particular emphasis on the behavior of systemic blood pressure under acute and chronic exposure to high altitude, and a focus on the possible occurrence and management of hypertension at high altitude.

The two components of the project are:

1) Lowlanders study – a randomized trial comparing the effects of combination of two antihypertensive agents vs. placebo in hypertensive subjects acutely exposed to high altitude

2) Highlanders study – a cross-sectional survey on the behavior of 24h ambulatory blood pressure among the subjects living permanently at high altitude

HIGHCARE-ANDES: Lowlanders study

RATIONALE Many subjects acutely exposed for recreational reasons to high-altitude are likely to be affected by cardiovascular problems, including hypertension, but little is known about the blood pressure responses to high altitude in subjects already affected by cardiovascular alterations, in particular by arterial hypertension, and even less is known about the effects of antihypertensive drugs and on their tolerability in this condition. Indeed, any recommendations published so far, regarding the management of hypertensive subjects planning to spend some time at high altitude, are mostly based on experts’ personal view rather than on solid scientific evidence.

STUDY OBJECTIVES AND DESIGN This is a parallel group, prospective, double-blind, placebo controlled randomized trial in mild hypertensive subjects residing permanently at sea level (district of Lima, Peru) that aims: 1) to assess the response of blood pressure to high altitude exposure in hypertensive subjects residing at sea level; 2) to assess the efficacy and safety of the combination of currently marketed anti-hypertensive drugs (the angiotensin receptor blocker telmisartan and the calcium channel blocker nifedipine GITS) in preventing a possible excessive blood pressure increase in hypertensive subjects when acutely exposed to high altitude; 3) to obtain the information on the genetic background of blood pressure response to high altitude. To meet the aforementioned objectives, before and during acute exposure to high altitude enrolled subjects will undergo several clinical and instrumental evaluations, including: conventional blood pressure and heart rate measurement, Lake Louise Score assessment, 24 h ambulatory blood pressure monitoring, echocardiography, arterial properties assessment, six minute walking test, cardiopulmonary exercise test, polysomnography with a portable device, pulmonary function tests, fluid balance chart, blood and urine analyses (electrolytes, creatinine, estimated GFR, glycemia, renin, angiotensin, aldosterone, plasma catecholamines, 24 h urinary sodium excretion, carbonic anhydrase activity and isoenzyme expression), a pre-specified genetic assessment.

HIGHCARE-ANDES: Highlanders study

RATIONALE There are very few data on the cardiovascular characteristics of subjects permanently living at high altitude, in particular when considering blood pressure levels and hypertension prevalence in these subjects. Interestingly, several such populations have distinct genetic characteristics facilitating the adequate function of cardiovascular system at high altitude. However, to our knowledge, no systematic study was ever performed to assess and characterize 24h blood pressure levels in the population of Andean highlands natives. Ambulatory blood pressure monitoring (ABPM) is a technique widely used in the routine clinical management of hypertension. This technique provides a much more accurate and detailed insight into the subject’s actual blood pressure behaviour over 24 hours compared with conventional office measurement, and previous findings from our group have demonstrating the feasibility of ABPM use at high altitude.

STUDY OBJECTIVES AND DESIGN The principal objective of this project is to assess, in a cross-sectional survey setting, the blood pressure level (by office blood pressure and 24 h ABPM measurement) and prevalence of hypertension in subjects residing permanently at high altitude (at 4430 m, Cerro de Pasco, Peru) and to obtain information on the genetic determinants of blood pressure in high altitude residents.