Independent at heart: persistent association of altitude with ischaemic heart disease mortality after consideration of climate, topography and built environment

Abstract

BACKGROUND: Living at higher altitude was dose-dependently associated with lower risk of ischaemic heart disease (IHD). Higher altitudes have different climatic, topographic and built environment properties than lowland regions. It is unclear whether these environmental factors mediate/confound the association between altitude and IHD. We examined how much of the altitude-IHD association is explained by variations in exposure at place of residence to sunshine, temperature, precipitation, aspect, slope and distance to main road. METHODS: We included 4.2 million individuals aged 40-84 at baseline living in Switzerland at altitudes 195-2971 m above sea level (ie, full range of residence), providing 77 127 IHD deaths. Mortality data 2000-2008, sociodemographic/economic information and coordinates of residence were obtained from the Swiss National Cohort, a longitudinal, census-based record linkage study. Environment information was modelled to residence level using Weibull regression models. RESULTS: In the model not adjusted for other environmental factors, IHD mortality linearly decreased with increasing altitude resulting in a lower risk (HR, 95% CI 0.67, 0.60 to 0.74) for those living >1500 m (vs<600 m). This association remained after adjustment for all other environmental factors 0.74 (0.66 to 0.82). CONCLUSIONS: The benefit of living at higher altitude was only partially confounded by variations in climate, topography and built environment. Rather, physical environment factors appear to have an independent effect and may impact on cardiovascular health in a cumulative way. Inclusion of additional modifiable factors as well as individual information on traditional IHD risk factors in our combined environmental model could help to identify strategies for the reduction of inequalities in IHD mortality. Independent at heart: Persistent association of altitude with ischemic heart disease mortality after consideration of climate, topography and built environment -a longitudinal cohort study ABSTRACTBackground Living at higher altitude was dose-dependently associated with lower risk of ischemic heart disease (IHD). Higher altitudes have different climatic, topographic and built environment properties than lowland regions. It is unclear whether these environmental factors mediate/confound the association between altitude and IHD. We examined how much of the altitude-IHD association is explained by variations in exposure at place of residence to sunshine, temperature, precipitation, aspect, slope and distance to main road.

Environmental Determinants of Cardiovascular Disease

“…A recent study, which included 4.2 million individuals aged 40–84 (nearly the complete adult population of Switzerland), found an inverse relationship between altitude and ischemic heart disease even after adjustment for sunshine, precipitation, temperature and road distance. 94 Although potential confounding by risk factors such as physical activity, obesity, high blood pressure and pollution levels, which all vary with altitude, 75 cannot be ruled out, the findings of the study support the concept that high altitude has an independent effect on cardiovascular health. Therefore, further studies are required to understand how altitude affects cardiovascular health and why it diminishes CVD risk.…”

Hypoxia-Inducible Factor Prolyl 4-Hydroxylases and Metabolism

“…According to WHO statistics a quarter of World's adults has metabolic syndrome, characterized by visceral obesity, dyslipidemia, hypertonia and hyperglycemia or insulin resistance, and which predisposes to type 2 diabetes (T2D), cardiovascular diseases, stroke and hepatic steatosis. Several epidemiological studies associate hypoxia in people living at high altitude with a lower prevalence of obesity, T2D, ischemic heart disease and mortality from it or from stroke, but with harmful effects on chronic obstructive pulmonary disease [12][13][14][15]. In addition, mouse data corroborate this.…”

Living at a Geographically Higher Elevation Is Associated with Lower Risk of Metabolic Syndrome: Prospective Analysis of the SUN Cohort

“…Regarding to living at high altitudes, several observational studies have reported lower incidence rates of metabolic diseases in different large cohorts (Ezzati et al, 2012; Voss et al, 2013, 2014; Woolcott et al, 2014; Faeh et al, 2016). Obesity was significantly higher at lower altitude category (<500 m) in an US cross-sectional study after controlling for urbanization, temperature, behavioral and demographic factors (males and females had 5.1 and 3.9 times the odds of obesity, respectively, compared to participants over 3000 m) (Voss et al, 2013).…”

“…In addition, two studies found an inverse association between altitude (more than 1500 m) and mortality from ischemic heart disease, while a positive association was established between altitude and mortality from chronic obstructive pulmonary disease (Ezzati et al, 2012). The mortality rate from coronary heart disease was also reduced in men living above 1220 m (Faeh et al, 2016). These outcomes are consistent with our results, although they enrolled participants living at considerably higher altitudes than those in our cohort (up to 3500 m vs. <2000 m in our study).…”

“…Concerning modifiable factors, the environment has been suggested to potentially influence the development of metabolic diseases (Friel et al, 2011; Dhurandhar and Keith, 2014; Valdes et al, 2014). Moreover, some studies on subjects living at high altitudes have reported lower incidence rates of conditions linked to MetS such as obesity (Voss et al, 2013; Woolcott et al, 2014; Diaz-Gutierrez et al, 2016), heart disease (Ezzati et al, 2012; Faeh et al, 2016), hypertension (Norboo et al, 2015) or type 2 diabetes (Woolcott et al, 2014). …”