Adverse clinical outcomes associated with sickle cell trait at high altitude.

Sickle cell trait (SCT) is a prevalent condition affecting more than 300 million individuals worldwide. Although formerly regarded as a benign carrier state, with complications rarely occurring outside of high-altitude or extreme physiologic conditions, recent population-level data has revealed an increased risk for chronic kidney disease (CKD) and pulmonary embolism (PE) in general populations. In this study, we sought to evaluate whether chronic, moderately high altitude exposure can increase the breadth and severity of SCT complications compared to sea-level cohorts. We used data from Colorado, which has the highest mean elevation of any State in the USA (2,070 m). We found that the risk for known SCT complications such as CKD and PE, as well as other clinical outcomes in which prior evidence was either weak or mixed, were significantly increased. In the latter category, adverse pregnancy outcomes including pre-eclampsia and intra-uterine death were particularly notable. The strength of the associations observed in this study generally exceeds prior reports and suggests that SCT patients living at high-altitude are at greater risk for morbidity than their sea-level counterparts.