The Authors Reply

We appreciate the letter from Dr. Swenson (2011). As he knows, many researchers in the last 40 years have shown the lower cardiovascular mortality in populations living at moderate altitudes and have attributed it to environmental hypoxia. However, we disagree with Dr. Swenson when he says that Winkelmayer et al. (2009) found no correlation between mortality and altitude below 1200 m. In the population actually studied of 800000 dialysis patients, the authors did find the relative mortality rate decreased significantly from the 76 m after adjusting for individual risk factors (Winkelmayer et al., 2009). In the general population these authors found significant decrease in mortality from 1200 m, but these data were secondary information in their article and could not be adjusted for potential confounders as those of patients (BMI, hemoglobin, etc.). In the general population of Switzerland the mortality rate from coronary heart disease (CHD) decreased with each 1000 m of altitude of residence, although data were also not adjusted for individual measurements of cardiovascular risk factors (Faeh et al., 2009). More recently, CHD mortality has been analyzed in all counties of continental America, and it has been found that the decrease occurs in men from 1000 m and in women from 300 m despite that, again, population data were general and without possibility of individual measurements to adjust for potential confounders (Ezzati et al., 2011). Interestingly, Ezzati et al. (2011) also found that, from an altitude as low as 200 m in men and 600 m in women, there was an increase in mortality from chronic obstructive pulmonary disease (COPD).

The hypothesis of increased air pollution arising from Swenson (2011) is interesting and cannot be completely ruled out. Nor can the influence of environmental conditions such as the gradual decrease in temperature with altitude that we mentioned in our article be discarded, But the inverse correlation between altitude and CHD mortality exists in industrial-polluted regions and also in nonindustrial regions, and it is not plausible that the continuous increase in COPD mortality from such low altitudes is attributable to a progressive reduction of pollution. Instead, environmental hypoxia has been experimentally verified: alveolar and arterial pressure of oxygen decreases significantly and progressively from 100 m altitude. And this is not without physiological effect: patients transported by helicopter rising from 60 m to 500–600 m suffer from the decrease of arterial oxygen [Schedler et al., 2004].

Few articles have studied the adaptation of large populations living in moderate altitudes adjusting for potential confounders (Winkelmayer et al. 2009; Baibas et al., 2005). In the enormous cohort of Winkelmayer, serum hemoglobin increased continuously from 76 m up to 1800 m. After Winkelmayer, the largest cohort is ours, describing a decrease in heart rate, leptin, and sCD40 from 200 m. Regardless of the small proportion of the Canarian population living above 600 m (10%), our sample was large enough to detect a significant correlation with heart rate elevation, leptin, and sCD40. Indeed, decreased leptin by hypoxia has been demonstrated (Norese et al. 2002).

Taken together there is little doubt that CHD mortality decreases with increasing altitude from sea level to moderate altitudes. The hypothesis of mild environmental hypoxia seems the most plausible.