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‘Cautiously reassuring’ picture emerges regarding sickle cell trait health risks
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Liem and colleagues report that sickle cell trait is not associated with objectively measured fitness levels or cardiovascular disease risk factors.
Utilizing data from the long-running Coronary Artery Risk Development in Young Adults (CARDIA) cohort, Liem and colleagues tested whether individuals with sickle cell trait had lower fitness levels and worse cardiovascular disease risk factor profiles as young adults, or if they were more likely to lose fitness or develop cardiovascular disease risk factors over a 25-year period into middle and late adulthood.
Strengths of the CARDIA study include its extended follow-up, as well as its multiple objective measurements of physical fitness and cardiovascular disease risk–factor phenotypes. The consistent absence of differences in either fitness or cardiovascular disease risk–factor profile between individuals with and without sickle cell trait observed by Liem and colleagues is very reassuring.
As noted in the study, concerns have been raised about an increased risk for exertion-related mortality associated with sickle cell trait. Some — but not all — exercise-based studies have suggested differences in physiologic responses to exercise among individuals with sickle cell trait compared with those without it. However, there has been a dearth of longitudinal, population-based studies of sickle cell trait–tested individuals necessary to adequately answer questions about health risks associated with sickle cell trait.
We conducted a study — published last year in The New England Journal of Medicine — that helped address this deficit. We found no association between sickle cell trait and mortality among black Army soldiers, all of whom are subjected to a similar, very demanding physical training environment. The article by Liem and colleagues is an important addition to this growing literature.
Epidemiologic studies have, however, demonstrated an increased risk for chronic kidney disease and for exertional rhabdomyolysis among black individuals with sickle cell trait. Interestingly, similar elevations in risk — on the order of a 50% relative increase — were reported by each study. Although statistically significant increases in risk are worrying, it is important to contextualize this relatively modest risk increase.
By comparison, equivalent — and often greater — increases in the risk for each of these conditions have been reported in association with very common and modifiable risk factors, such as obesity, tobacco use, socioeconomic status and, for exertional rhabdomyolysis, medication use. Further, the quite low population attributable risk (6%) reported in association with sickle cell trait for chronic kidney disease reflects the relatively small contribution expected to be made by sickle cell trait to the total disease burden.
The study by Liem and colleagues is important due to its focus on risk factors for heart disease, which has been the leading cause of death for decades. Its findings, in combination with our article and our ongoing work, indicate that a cautiously reassuring picture may be emerging regarding the health risks associated with sickle cell trait.
However, more work is needed to confirm these findings and to map the other diverse health effects associated with sickle cell trait. This work is critical to ensure that clinicians neither underestimate risks, nor engage in excessive precautions that might serve only to stigmatize persons with the trait.
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For more information:
Lianne M. Kurina, PhD, is associate professor of medicine at Stanford University School of Medicine. She can be reached at lkurina@stanford.edu.
D. Alan Nelson, MPAS, PhD, is a postdoctoral scholar at Stanford University School of Medicine. He can be reached at nelsonal@stanford.edu.
Disclosure: Kurina and Nelson report no relevant financial disclosures.