Antonio de Leon et al. (2011) report in a recent issue of the journal a number of highly significant correlations between altitude of residence and hemodynamic/metabolic parameters in a population survey of roughly a thousand Canary Islands citizens. The authors report that higher altitude residence favorably alters heart rate and several serum markers of inflammation and fat metabolism, and proceed to speculate that these changes may help explain many reported studies of lower overall mortality and greater life expectancy in populations living at moderate to high altitudes. Many of these studies (given in their reference list) included populations living considerably higher than 600 m, an altitude above which only 10% of their studied subjects reside and so only contribute minimally to the observed correlations. In the largest population studies of the question of altitude and mortality in the United States (Winkelmayer et al., 2009) and in the German-speaking cantons of Switzerland (Faeh et al., 2009) comprising over 2,400,000 people, the authors found no discernable correlation of altitude with reduced mortality rates below an altitude of 1200 m.
The authors conclude, as would most readers, that altitude-related hypoxia is the major basis for these observations, and yet it is very difficult to imagine that the slight reduction of inspired oxygen up through 600 meters or about 1800 feet (a fall in inspired oxygen from 149 to 137 mmHg) represents a significant hypoxic stimulus to link their findings to the putative mortality reduction of high altitude living. Donoghue et al. (2005) found that sea level residents taken into a normobaric chamber for 5 days at an inspired Po2 sufficient to lower arterial Po2 by 10 mmHg (roughly equivalent to 600 m) showed no decrease in arterial Pco2 as a reflection of increased ventilation—a hallmark of hypoxic responsiveness. As another measure of hypoxic response, populations living at 1600 m or below do not differ in hematocrit from those at sea level (Sullivan et al., 2008; Weil et al., 1968). The lack of hematocrit change at altitudes below 1600 m accords with the inconsistent data on detectable erythropoietin release in humans until the inspired oxygen is lowered below 16%–17% (MacKenzie et al., 2008). These data then do not suggest sufficient hypoxia to account for any salutary effect on mortality postulated in studies of people living below about 1200 to 1600 m.
What then might account for the metabolic changes noted by de Leon et al. (2011) and for the mortality reduction noted in population surveys of people living at only modest elevations? A more compelling answer is air pollution associated with much more densely populated areas, the majority of which are at low altitude (Beelen et al., 2009). It is well established that ambient pollution, both particulate and nonparticulate, are pro-inflammatory and correlate in a dose response fashion with increased death and hospitalization rates for a number of cardiopulmonary conditions (Gill et al., 2011; Pope et al., 2009; van Eaden et al., 2005). Do the authors have pollution measurements in their database to assess this possibility or can they more convincingly argue on physiological grounds that the hypoxia below 600 m is a more potent stimulus than I have discussed?
