Social Determinants of Health Impact Sickle Cell Disease Mortality in US

Social determinants of health (SDOH) influence mortality rates in adults with sickle cell disease (SCD) in the United States, according to a cross-sectional study using the Centers for Disease Control and Prevention (CDC) social vulnerability index (SVI) database.¹

Nearly 100,000 people have SCD in the US, with approximately 1 of every 365 African Americans born with SCD.² This analysis of the CDC’s dataset revealed greater SCD-related mortality in US counties with a higher SVI quartile, which remained across a variety of demographic subsets, including age, sex, and ethnicity and race.¹

“This finding highlights the ultimate need for enhanced access to specialized and comprehensive SCD care because treatment advancement alone does not directly translate to improvement in nationwide mortality,” wrote the investigative team, led by Modupe Idowu, MD, McGovern Medical School at the University of Texas Health Science Center at Houston.

Hydroxyurea, a disease-modifying agent for SCD, was approved by the US Food and Drug Administration (FDA) in 1998, with data confirming a significant reduction in mortality by 40%.³ However, a lack of patient adherence to hydroxyurea and disadvantaged socioeconomic status are noted roadblocks to its use in SCD. Newer disease-modifying therapies for SCD have also emerged since 2017, but have not necessarily improved population-level mortality rates.⁴

Citing the potential impact of SDOH on SCD-related outcomes, Idowu and colleagues assessed the correlation between SDOH and SCD mortality in the SVI dataset from 2016 to 2020.¹ The dataset combined county-level data from the CDC and Agency for Toxic Substances and Disease Registry SVI with SCD mortality data from the CDC WONDER database.

Social factor categories, including socioeconomic status, household composition and disability, minority status and primary language, and housing type and transportation, comprised the index. The SVI ranged from 0 to 1, with 0 representing the lowest vulnerability and 1 the highest. US countries were divided into 4 quartile models, according to the SVI score: SVI-Q1, 0.00–0.25; SVI-Q2, 0.26–0.50; SVI-Q3, 0.51–0.75; SVI-Q4, 0.76–1.00.

For the analysis, Idowu and colleagues evaluated the age-adjusted mortality rates (AAMRs) per 1,000,000 individuals, standardized to the 2000 US census population. They further calculated rate ratios (RRs) by comparing county-specific AAMRs of SVI-Q4 with SVI-Q1.

Among 1,633,737,771 individuals in the dataset, there were 2635 deaths from SCD (1289 male [49.1%] and 1336 female [50.9%]). Most deaths occurred in SVI-Q4 (n = 1480), followed by Q3 (n = 687), Q2 (n = 344), and Q1 (n = 114)—higher SVI was linked to 1366 excess deaths in the US.

Upon analysis, higher SVI was correlated with 2.11 excess deaths per 100,000 individuals (RR, 4.90; 95% CI, 4.81–5.00). Higher mortality trends with higher SVI were identified in male (RR, 4.56; 95% CI, 4.44–4.69) and female (RR, 5.85; 95% CI, 5.68–6.03) patients with SCD.

Higher SVI was also linked to higher mortality rates across 3 different age groups, with middle-aged (25–54 years) patients with SCD experiencing the highest mortality in Q4, at 3.45 excess deaths per 1,000,000 individuals (RR, 4.97; 95% CI, 4.85–5.09).

Mortality rates were highest in African American patients among racial groups, with higher SVI linked to 2.29 excess deaths per 1,000,000 individuals (RR, 1.24; 95% CI, 1.22–1.27). In contrast, higher SVI was associated with 0.12 excess deaths per 1,000,000 individuals in White patients.

Metropolitan regions experienced higher SCD-related mortality than non-metropolitan regions. After stratification by census region, Idowu and colleagues found the highest level of SCD-related mortality in the Northeast, with a higher SVI linked to 3.16 excess deaths per 1,000,000 individuals (RR, 8.02; 95% CI, 7.66–8.40).

“Supported by evidence from current literature, our study demonstrates that despite advancements in medical therapy for SCD, health inequities persist,” investigators wrote. “Patients from areas with higher SVI faced up to 6 times higher risk of death compared with those from areas with lower SVI.”

References

1. _{Tan JY, San BJ, Yeo Y, et al. Social Vulnerability and Sickle Cell Disease Mortality in the US. JAMA Netw Open. 2024;7(9):e2440599. doi:10.1001/jamanetworkopen.2024.40599}
2. _{Payne AB, Mehal JM, Chapman C, et al. Trends in Sickle Cell Disease-Related Mortality in the United States, 1979 to 2017. Ann Emerg Med. 2020;76(3S):S28-S36. doi:10.1016/j.annemergmed.2020.08.009}
3. _{Steinberg MH, Barton F, Castro O, et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment [published correction appears in JAMA. 2003 Aug 13;290(6):756]. JAMA. 2003;289(13):1645-1651. doi:10.1001/jama.289.13.1645}
4. _{Kavanagh PL, Fasipe TA, Wun T. Sickle Cell Disease: A Review. JAMA. 2022;328(1):57-68. doi:10.1001/jama.2022.10233}