Cardiometabolic risk factors in native populations living at high altitudes

It is generally accepted that metabolic changes that take place in individuals exposed to high elevation are because of ambient hypoxia, which occurs as a consequence of a low total atmospheric pressure. The discovery of hypoxia inducible factor 1 (HIF1), a transcription factor, has been a breakthrough in the understanding of adaption to high altitudes.

The purpose of the present review was to discuss specific epidemiological aspects of cardiovascular disease (CVD) risk factors and their mechanisms in vulnerable, understudied populations living at high altitudes.

Obesity prevalence has been inversely associated with elevation. HIF1 has been related to plasma leptin--a hormone secreted by adipose tissue that produces negative feedback on appetite--and inversely associated with obesity. Diverse factors, such as genetics, chronic hypoxia, diet and lifestyle behaviours, could have an influence on the high dyslipidaemia rates of high-altitude natives. Hypoxia could mediate the effects of altitude on human physiology, including lipid metabolism. Genetic studies suggest that dyslipidaemia could be related to the HIF1. Hypoxia inhibits oxidative phosphorylation and stimulates the oxygen signalling pathway through the HIF1. Low fasting glycaemia in individuals at high altitudes has been shown. An increased GLUT4 protein content in skeletal muscle in response to hypoxia has been reported and could be associated with lower glucose levels. Given the high prevalence of dyslipidaemia and the low prevalence of obesity and diabetes in these impoverished high-altitude communities, changes in lifestyle including decreased physical activity and the consumption of a more westernised diet would likely increase the prevalence of CVD related mortality.

Control over major CVD risk factors, when identified early, could be the key to reducing morbidity and mortality in patients with limited access to medical services such as Native populations.