The main effects of acute HA exposure
HIGHCARE (High Altitude Cardiovascular Research) program is a multidisciplinary scientific project which yielded a series of studies conducted in different HA regions, including the European Alps, Himalaya (Mount Everest), and the Andes in the last 20 years. The research aimed to explore the changes and adaptation mechanisms of cardiovascular and respiratory systems occurring in individuals exposed to HA hypobaric hypoxia. The observed effects of hypobaric hypoxia included hyperventilation and interstitial pulmonary edema; an increase of heart rate, cardiac output, and BP, accompanied by direct pulmonary vasoconstriction, and cerebral vasodilatation. There was an increased hemoglobin affinity for O2 accompanied by a rise of hematocrit. Furthermore, a rise in ANP and ADH levels were noted, as well as increased sodium bicarbonate renal excretion as a response to hypocapnia and respiratory alkalosis. Other changes included sleep disturbances and metabolic changes similar to metabolic syndrome (1). The observed changes were dependant on the duration of an individual’s exposure to altitude, age, the partial pressure of O2 in arterial blood, and minute ventilation. Some of these mechanisms activated almost immediately, whereas others needed hours to days to attain full expression.
The effects of HA on BP have also been monitored, considering that renin-angiotensin system activity changes with altitude. Conventional and ambulatory BP was measured at baseline and on-treatment with an angiotensin receptor blocker in healthy voluteers : after 8 weeks at sea level, and under acute exposure to 3400 and 5400 m altitude, the latter upon arrival and after 12 days (Mt. Everest base camp). The results showed a progressive increase of ambulatory BP with increasing altitude, which remained elevated after 3 weeks (2). The antihypertensive effects of the angiotensin receptor blocker were evident at sea level and at 3400m, but disappeared during the first week at 5400m due to suppression of renin-angiotensin-aldosterone system during acute exposure to such a very high altitude.
The effects of altitude on BP were explored also in hypertensive patients living in Peru at sea level and brought to an altitude of 3260 m for a few days. In the Peruvian Study, one hundred subjects with mild, untreated hypertension were randomized to double-blind placebo and angiotensin receptor blocker ̶ calcium channel blocker combination. Twenty-four-hour ambulatory BP monitoring was performed off-treatment, after 6 weeks of treatment at sea level, on treatment during acute exposure to HA (3260m), and immediately after return to sea level. 24-hour BP increased significantly during acute HA exposure in hypertensive subjects, however, the treatment with angiotensin receptor blocker ̶ calcium channel blocker combination provided effective protection in these circumstances (3).
Another study evaluated the effects of HA on diuresis and related mechanisms. Cardiovascular, endocrine, and renal responses to stepwise acute exposure to simulated altitude (6,000m) were compared in ten acclimatized recumbent mountaineers after descending from Himalayan altitudes of at least 4,000m and ten non-acclimatized recumbent volunteers for a mean of 24 days. The results showed that natriuresis and diuresis typified the renal responses to altitude exposure of both the acclimatized, as well as non-acclimatized subjects. This led to the conclusion that the renal effects were mediated by atrial natriuretic peptide release and slight suppression of arginine-vasopressin (AVP) secretion. Increased urine flow at altitude offset the cardiac (volume) overload, resulting from hypoxic stimulation of the arterial chemoreceptors. Enhanced AVP secretion, as found in the non-acclimatized subjects at and above 4000 m, coincided with inadequate altitude adjustment (4).
The effects of chronic HA exposure
Regarding chronic altitude exposure, the HIGHCARE Andes Study investigated differences between individuals residing in Cerro de Pasco, a mining town at 4550 m of altitude in the Peruvian Andes, and individuals living in Lima, at sea level. The prevalence of hypertension was low but not negligible among Andean HA dwellers. Higher rates of hypertension were observed with ambulatory as compared to office BP measurements. Relevant differences were observed in factors associated with daytime vs. night-time and diastolic vs. systolic hypertension. Polycythemia and chronic mountain sickness appeared to be strongly associated with ambulatory hypertension among highlanders (1).
High altitude hypoxic conditions exhibit several effects on the kidney depicted as High-Altitude Renal Syndrome. This condition is characterized by polycythemia, hyperuricemia, microalbuminuria, and increasing BP. ACE inhibitors appear effective at reducing proteinuria and lowering hemoglobin levels in these patients (5).
Recommendations for patients exposed to HA conditions
Based on the gathered evidence of the effects of HA on the human organism and system functions, we should increase awareness of altitude effects in persons with pre-existing cardiovascular and renal conditions. They should be advised on the importance of adequate preparation for the ascent, which should incorporate physical training and health status checks. If necessary, their chronic therapy should be revised and adjusted to expected conditions. The journey should be well planned, with a pre-determined speed of ascent, degree of physical activity, and altitudes at which to sleep to avoid possible adverse events.