The relative risk of ERD explained by preexisting disease (largely silent heart disease) was 2.3 for Hb AS , but this was not statistically significant. The relative risk of ERD unexplained by preexisting disease was 28 for Hb AS. This was highly significant with p less than one per thousand. The relative risk ratio has since been corrected to 30 (3). If one eliminates restrictions by race and cause of ERD, the risk of exercise-related death for sickle cell trait was 28-fold. The excess ERDs with sickle cell trait seemed to result from the immediate stress of exercise. About 50% of cases resulted from exertional heat illness and the remaining cases were idiopathic sudden deaths (ISD). Clinical features and distribution of cases between EHI and ISD did not differ by the presence or absence of hemoglobin S, except that rhabdomyolysis was the predominant form of EHI among cases with sickle cell trait (3).
We examined the effect of age on risk of ERD unexplained by preexisting disease. There was an eight-fold increase in mortality going from age 17-18 to age 28-29 among recruits with Hb AS but no such trend for recruits without sickle cell trait (3, 9). This difference in effect of age suggests that there may be a difference in pathogenesis of death depending on the presence or absence of hemoglobin S. This effect might be due to renal papillary necrosis from Hb AS, a lesion increasing linearly in severity with age and present in at least 80% of recruits (figure 1 in 3, 6). The resulting deficit in renal concentrating ability might predispose that person toward more severe EHI since obligatory loss of free water might increase the hyperosmolar state important in the pathogenesis of EHI.
We were surprised by the high excess mortality associated with sickle cell trait. It is often said that the absolute risk of mortality with sickle cell trait we reported was low (12, 13). This excess mortality was one per three thousand recruits with sickle cell trait or one death per 60 to 90,000 person-hours of exercise equivalent to middle distance running. This mortality rate for 18 year old recruits is about 4 to 7 times higher than the mortality observed from artherosclerosis among middle aged runners: one death per 400,000 hours of running (14). Other population surveys of sickle cell trait have shown only mild effects of trait on hospitalization rates and none on mortality rates (3). Whereas our survey observed 5,000 person-years of exposure (38,600 people with Hb AS for a median of 8 weeks exposure) (9), other surveys of young adults with sickle cell trait examined exposures two to four logs smaller.
Too old. Excessive mortality at 28 gives you 16 good breeding years to begin with, and considering that life expectancy in stone age societies is/was around 30-35, you're not even losing that much in the end anyway. By contrast, the majority of malaria deaths (70-80%) occur in children under 5, accounting for as much as 30% of childhood mortality before age 5 in endemic malarial zones.
It's all about getting you to breeding age - anything after that is purely a bonus as far as natural selection is concerned.