Sickle cell trait unrelated to fitness level, heart failure

Black sickle cell trait carriers do not have lower cardiopulmonary fitness levels and are at no greater risk for hypertension, diabetes or metabolic syndrome as they transition to middle age, according to a population-based study published in Blood.

“We sought to understand if having sickle cell trait has an effect on someone’s baseline fitness levels or changes in their fitness over time,” Robert I. Liem, MD, director of the comprehensive sickle cell program and associate professor of pediatrics at Northwestern University Feinberg School of Medicine, said in a press release. “Based on our findings, there is no evidence that carriers of sickle cell trait are less fit or become less fit with time compared to people who do not have sickle cell trait.”

Sickle cell trait affects more than 100 million people worldwide and is observed in 8% of the black population in the United States. It is caused by the inheritance of a single copy of the variant B globin gene, which results in production of abnormal sickle hemoglobin. The co-inheritance of two copies of the abnormal gene results in sickle cell anemia, a clinically significant blood disorder seen primarily among individuals of African or Afro-Caribbean descent.

Historically, sickle cell trait has been considered a clinically benign condition. However, recent studies suggest sickle cell trait may carry a higher risk for chronic kidney disease, thrombosis, stroke and pregnancy-related complications in its carriers.

There also is growing concern sickle cell trait may be associated with sudden death during strenuous physical activity and exercise, leading to the National Collegiate Athletic Association requiring carrier status testing among all student athletes. Sickle cell trait status also was shown to be associated with a significantly high risk for exertional rhabdomyolysis among black soldiers on active duty in the U.S. Army.

In their study, Liem and colleagues evaluated data from 2,631 black men and nonpregnant women aged 18 to 30 years who were part of the Coronary Artery Risk Development in Young Adults group recruited from four urban areas — Birmingham, Oakland, Chicago and Minneapolis — between 1985 and 1986.

The study included follow-ups at 2, 5, 7, 10, 15, 20 and 25 years.

Of the participants, 2,037 had available sickle cell trait genotype (n = 539 missing) and fitness data at baseline (n = 55 missing).

Researchers excluded participants with sickle cell disease (n = 3), participants who underwent bariatric surgery (n = 36) and those missing baseline covariates of interest (n = 3), leaving a final cohort of 1,995 participants, 6.8% of whom were determined to have sickle cell trait (n = 136). Mean age was 24.8 years for those with sickle cell trait and 24.3 years for those without sickle cell trait.

At baseline, diastolic blood pressure was slightly higher in the sickle cell trait group (71 Hg vs. 69 Hg, P = 0.02), although the prevalence of hypertension, diabetes and metabolic syndrome was similar between the two groups. Researchers reported no significant difference in baseline fitness parameters, even after adjusting for age, sex, reported physical activity and BMI.

Adjusted mean duration of exercise (535 vs. 540 seconds) also was similar in participants with or without sickle cell trait, as were adjusted estimated METs (11.6 units vs. 11.7 units), maximum heart rate achieved (174 bpm vs. 175 bpm) and heart rate at 2 minutes of recovery (44 bpm vs. 43 bpm).

Liem and colleagues reported no significant annual changes over 20 years in graded exercise performance, including test duration, estimated METs, maximal heart rate achieved or heart rate at 2 minutes of recovery between participants with or without sickle cell trait.

There also was no significant association between sickle cell trait status and incident hypertension (HR = 1.22; 95% CI, 0.91-1.65), diabetes (HR = 1.48; 95% CI, 0.96-2.27) or metabolic syndrome (HR = 1.26; 95% CI, 0.92-1.74) over 25 years of testing.

Researchers noted the relatively low prevalence of sickle cell trait carriers in their cohort and the number of participants excluded due to missing genotype data as study limitations.

“Although this study examined fitness levels in adults with sickle cell trait, it did not specifically evaluate exercise safety,” Liem said. “From what we know from other studies, however, it is recommended that people with sickle cell trait who exercise, especially competitive and elite-level athletes, remain hydrated and know the symptoms of exertion-related rhabdomyolysis, a condition that causes the breakdown of muscles and has been associated with sickle cell trait. It is also important to make others aware of those symptoms.” – by Chuck Gormley

Disclosure: The researchers report no relevant financial disclosures.