RESULTS
The analytical sample included 709 patients. The geographic distribution
of the population is visualized in Figure 2 with wide spread of
the subjects and increased concentration around the major cities of
north and central Alabama. Characteristics of the sample, overall and by
ACS status, are presented in Table 1 . Median age was 13.6
years, and the majority (72%) had public health insurance. Those who
resided in highly deprived areas made up 45% of the sample, while 21%
resided in neighborhoods that were ≥90% African American in
composition, and 17% resided in rural areas. The most prevalent
phenotype was the SS phenotype (54%). When compared to children with
non-recurrent ACS (no ACS and single ACS), those with recurrent ACS were
older (IRR 1.05, CI 1.02–1.07, p<0.001), more likely to have
asthma (IRR 3.93, CI 2.84–5.44, p<0.001), to be a male (IRR
1.91, CI 1.36–2.68, p<0.001), and to be on chronic blood
transfusion (IRR 1.78, CI 1.26–2.52, p=0.001) and hydroxyurea (IRR 6.3,
CI 4.01–9.91, p<0.001). Recurrent ACS was lower among those
living in a highly deprived area (IRR 0.72, CI 0.52–0.99, p=0.044) and
in a predominantly African American community (IRR 0.56, CI 0.35–0.90,
p=0.017).
To assess the adjusted association between residential characteristics
and ACS categories (no ACS, single ACS, any ACS, non-recurrent ACS, and
recurrent ACS), we estimated a separate model for each neighborhood
characteristic (Model 1: deprivation; Model 2: racial composition; Model
3: rurality) and a full model with all three neighborhood
characteristics together (Model 4) Table 2 . All four models
controlled for the same covariates: age, sex, insurance type, BMI,
chronic transfusions, hydroxyurea, asthma, and phenotype. Residence in
high-deprivation neighborhood was associated with 27% lower risk of
recurrent ACS vs non-recurrent ACS, 43% lower risk of recurrent ACS vs
single ACS, and 42% lower risk of recurrent ACS vs no ACS (Model 1,Table 2 ). Residence in predominantly African American
neighborhood was associated with 43% lower risk of recurrent ACS vs
non-recurrent ACS, 57% lower risk of recurrent ACS vs single ACS, and
59% lower risk of recurrent ACS vs no ACS (Model 2, Table 2 ).
However, when all residential characteristics were assessed together,
area deprivation was no longer significant while neighborhood racial
composition remained significant, indicating that the neighborhood’s
racial composition accounts for the association between socioeconomic
deprivation and decreased ACS recurrence (Model 4, Table 2 ). A
separate analysis showed that those who reside in a predominantly
African American neighborhood are 1.24 times more likely to reside in a
socioeconomically deprived neighborhood (CI 1.04–1.48, p=0.016).
Rurality was not associated with ACS, neither by itself (Model 3,Table 2 ) nor together with the other neighborhood
characteristics (Model 4, Table 2 ). There was no difference in
residential characteristics when comparing single ACS to no ACS
(Table 2 ).
Multiple regression of recurrent ACS adjusted for all covariates showed
that males have nearly two-fold risk of recurrent ACS compared to
females Table 3 . Clinical covariates associated with increased
risk of recurrent ACS included asthma (IRR 2.62, CI 1.89–3.63,
p<0.001) and being on hydroxyurea (IRR 2.89, CI 1.74-4.8,
p<0.001). In contrast, patients with the SB+ and SC phenotypes
had 82% (CI 0.04–0.72, p=0.015) and 66% (CI 0.19–0.61,
p<0.001) less risk of recurrent ACS compared to those with the
SS phenotype. Because asthma was a significant risk factor for recurrent
ACS, in a separate analysis we assessed the relationship between living
in a highly deprived area and having asthma, but found no significant
association (IRR 1.10, CI 0.93–1.30, p=0.28).
Next, we sought to determine if the adverse relationship of neighborhood
socioeconomic deprivation with recurrent ACS is explained by access to
care. While mild ACS may be managed at home or local hospitals, severe
ACS has to be managed in a tertiary pediatric hospital with intensive
care unit abilities. We therefore used the medical records to determine
the severity of ACS (mild vs severe) and replicated the model build-ups
to determine the odds of experiencing severe ACS. These additional
analyses found no association between neighborhood characteristics and
ACS severity Supporting Information Table S1 , indicating that
the association of neighborhood characteristics with recurrent ACS is
not explained by access to care. We also estimated a model of ACS
recurrence with distance to the hospital in miles as another marker of
access to care, and again found no significant associationSupporting Information Table S2 .
Finally, we performed sensitivity analyses where all area-level measures
were treated as continuous variables Supporting Information
Table S2 . These analyses confirmed a dose-response relationship between
neighborhood socioeconomic deprivation, neighborhood racial composition,
and recurrent ACS. We also tested for interactions between neighborhood
socioeconomic deprivation and each of rurality and racial compositionSupporting Information Table S3 . None were found to be
significant, suggesting that the likelihood of recurrent ACS does not
vary by the relationship between deprivation and rurality or racial
composition.