Studies Challenge Assumptions About Sickle Cell Trait and Cardiovascular Health: New data suggest sickle cell trait is not associated with heart failure or diminished fitness recovery

Sickle cell trait (SCT) is a poorly understood condition, and there are many unanswered questions about the effect it has on carriers. While many people with SCT live normal, healthy lives, others have a higher risk of adverse health outcomes. 

SCT, which affects more than 100 million people worldwide, occurs when an individual inherits a single copy of the gene that causes sickle cell disease. It is not a disease, but it has been associated with an increased rate of blood clots, kidney disease, and pregnancy-related complications. The association between SCT and cardiovascular events has not been extensively studied. Previous research suggests there is a link between SCT and sudden death from over exertion; however, this has been challenged by recent evidence.  [1]

Two new studies published in  Blood, the Journal of the  American Society of Hematology(ASH), address the need for improved understanding of SCT. These studies present valuable data on the cardiovascular health and fitness of individuals with SCT, suggesting that they face no greater risk of heart failure nor have diminished fitness compared to people without the trait.

Longitudinal Association among Sickle Cell Trait, Fitness, and Cardiovascular Disease Risk Factors in African Americans in CARDIA (Liem, et al.)

Based on this analysis, researchers report that SCT is not significantly associated with longitudinal changes in fitness, nor is it an independent risk factor for hypertension, diabetes, or metabolic syndrome among African Americans.

“We sought to understand if having sickle cell trait has an effect on someone’s baseline fitness levels or changes in their fitness levels over time. 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,” said study author Robert Liem, MD, of the Ann & Robert H. Lurie Children’s Hospital of Chicago and Feinberg School of Medicine at Northwestern University. 

Dr. Liem and colleagues analyzed data from the 25-year longitudinal CARDIA study (Coronary Artery Risk Development in Young Adults), which compared exercise performance (running on a treadmill), hypertension, diabetes, and metabolic syndrome rates across different populations. CARDIA included more than 5,000 patients 18-30 years old who were enrolled in four cities (Birmingham, AL; Oakland, CA; Chicago, IL; and Minneapolis, MN). People were enrolled from 1985-1986, and follow-up data were collected at 5, 7, 10, 15, 20, and 25 years. Dr. Liem’s analysis focused on the 1,995 African American adults in CARDIA, 7 percent of whom had SCT, which is comparable to the national rate. 

The team found no significant increase in diabetes (23% incidence in SCT carriers vs. 17% in non-carriers), hypertension (61% vs. 57%), or incident metabolic syndrome (45% vs. 40%), which represent risk factors for cardiovascular disease. Furthermore, exercise performance over 20 years was similar for those with and without SCT. 

“Although this study examined fitness levels in adults with sickle cell trait, it did not specifically evaluate exercise safety. 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.”

Dr. Liem also noted that CARDIA will continue to track cohort patients for the foreseeable future.

Sickle cell trait is not associated with an increased risk of heart failure or abnormalities of cardiac structure and function in African Americans (Bello,Hyacinth et al.

In this study, researchers analyzed data from four longitudinal cohorts with a combined sample of more than 15,000 African Americans – 1,216 with SCT – and determined that SCT is not independently associated with an increased risk of heart failure. 

“We know that individuals who have sickle cell disease have an increased risk for abnormal heart structure and function which results in poor cardiovascular outcomes,” said co-lead study author Natalie Bello, MD, MPH, of NewYork-Presbyterian/Columbia University Medical Center in New York. “We conducted this study because there is a lack of information about the heart structure and function of people with SCT and their risk of developing heart failure.”

Dr. Bello and colleagues conducted a meta-analysis of the incidence of heart failure from four independent population-based cohorts in the United States. The prevalence of SCT among the cohorts ranged from 7-9 percent and was consistent with population prevalence estimates in African Americans. 

The researchers found that individuals with SCT had no greater risk of developing heart failure compared to those without SCT. Heart failure was observed in 7.6 percent of the SCT carriers compared to 8.6 percent of the non-carriers. There were also no significant differences in cardiac structure and function, including no observed differences in abnormalities of left ventricular size, thickness, or systolic function. Additionally, recognizing that SCT results in a higher incidence of blood clots and pulmonary embolism, the team looked for signs of increased stress on the right ventricle, which could see greater stress and higher pressures as a result, but found none.  

“What is significant about this study is that it is the first of its kind and more representative of the African American population in the United States compared to earlier studies” said co-lead study author Hyacinth I. Hyacinth, MBBS, PhD, MPH, of Aflac Cancer and Blood Disorder Center, Children’s Healthcare of Atlanta and Emory University in Atlanta. “Not only does the sample reflect the rate of sickle cell trait that we see nationwide, but we also saw very similar rates of obesity, hypertension, and diabetes.”

The cohorts that contributed to this study include: Atherosclerosis Risk in Communities Study (ARIC); Jackson Heart Study (JHS); Multi-Ethnic Study of Atherosclerosis (MESA); and Women’s Health Initiative (WHI). Additional analysis is being done on these data to assess the other effects that SCT can have on cardiac events such as myocardial infarction.

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Blood (  www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (  www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.

ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology. 

blood® is a registered trademark of the American Society of Hematology.

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Studies Challenge Assumptions About Sickle Cell Trait and Cardiovascular Health: New data suggest sickle cell trait is not associated with heart failure or diminished fitness recovery

Studies Challenge Assumptions About Sickle Cell Trait and Cardiovascular Health: New data suggest sickle cell trait is not associated with heart failure or diminished fitness recovery

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