Sickle Cell Trait from a Metabolic, Renal, and Vascular Perspective: Linking History, Knowledge, and Health

Sickle cell trait (SCT) is at the intersection of genetics, social policy, and medicine. SCT occurs in three-hundred million people worldwide and in approximately 8 % of African-Americans. There has been great debate about the influence of SCT on health. Yet data exist, albeit controversial, which suggest that SCT is associated with metabolic derangements that can lead to sudden death after vigorous physical activity, renal dysfunction, thromboembolic events, and stroke. In addition, it has even been postulated that SCT might enhance the vascular complications of diabetes. This review focuses on (a) the scientific breakthroughs that led to the discovery of hemoglobin S, sickle cell disease, and SCT, (b) the history of screening programs in the United States, (c) the incidence and etiology of exercise-related sudden death in military personnel and athletes with SCT, and (d) the data examining the potential chronic disease consequences of SCT from a metabolic, renal, and vascular perspective.