RESULTS:
The primary analysis included a total of 4,022 pregnant individuals (Figure 1). High allostatic load was identified in 33.0% (n=1327) of individuals. Maternal age, race, gravidity, prior miscarriage, prior bleeding at the first trimester, and insurance status were associated with high allostatic load (Table 1)
The composite outcome was identified in 36.4% (n=1,462) individuals; 1079 (26.6%) had HTN, and 636 (15.4%) had MD. The time between index pregnancy and HHS, maternal age, race, education, gravidity of 3 or more, smoking status, and government health insurance were associated with CVD outcomes, while other maternal characteristics were not (Tables S1, S2, and S3). High allostatic load (OR= 2.1; 95% CI: 1.8-2.4) was significantly associated with composite outcome. After adjustment for the time between index pregnancy and HHS, maternal age, race, education, smoking status, gravidity, smoking status, bleeding in the first trimester, prior adverse pregnancy outcomes, and government health insurance status, allostatic load remained significantly associated with composite outcome (aOR 2.0, 1.8-2.3), (Table 2).
Associations persisted in the analysis of both components of composite outcome. In bi-variable analysis, a high allostatic load was associated with HTN (OR= 2.1; 95% CI: 1.8-2.4) and MD (OR= 1.9; 95% CI: 1.6-2.2). In an adjusted model, HTN and MD remained significantly associated with high allostatic load (aOR= 2.1; 95% CI: 1.8-2.4), and (aOR= 1.7; 95% CI: 1.5-2.1), respectively. Results were similar in the sensitivity analysis, where we included prior APOs: composite outcome (aOR = 1.9; 95% CI: 1.6-2.2), HTN (aOR = 1.9, 95% CI: 1.6-2.2), and MD (aOR = 1.8, 95% CI: 1.5-2.1) (Table 2).
In the exploratory analyses, the individual components of allostatic load: BMI, DBP, SBP, triglycerides, HDL, creatinine, and CRP, were significantly associated with composite outcome, HTN, and MD while others were not. In addition, glucose was associated with composite outcome and MD, LDL was associated with composite outcome, and HTN and total cholesterol were associated with composite outcome (Table S4). In a sensitivity analysis, an allostatic load score excluding both DBP and SBP remained significantly associated with composite outcome (aOR = 1.9, 95% CI: 1.6-2.2), HTN (aOR = 1.7, 95% CI: 1.5-2.0). Similarly, an allostatic load index excluding insulin remained significantly associated with MD (aOR = 1.9, 95% CI: 1.6-2.3) (Table S7).
High allostatic load was a partial mediator in the association between race and composite outcome, but not the individual components HTN or MD (Table 3). In greater detail, first, we established a significant association between race and composite outcome (path c, Table 3), race and high allostatic load (path a, Table 3), and high allostatic load and composite outcome (path b, Table 3). The magnitude of the relationship between race and composite outcome in the presence of high allostatic load was modestly smaller (path c’ vs. path c, Table 3). For composite outcome components, HTN and MD, a significant association between race and each outcome was present (path c). The association between race and high allostatic load is significant (path a). The association between allostatic load and each component of CVD outcomes was significant (path b). However, we did not see a reduction in the magnitude of the relationship between race and each component of the composite outcome with the addition of high allostatic load. Thus, high allostatic load was not demonstrated to mediate the association between race and HTN or MD (Table 3). In a sensitivity mediation analysis where we restricted the population to examine the association of allostatic load and CVD between non-Hispanic Black and non-Hispanic White individuals, results were similar in magnitude, significance, and interpretation (Table S5).
In the exploratory analysis testing whether race moderates the relationship between allostatic load and composite outcome, the association between allostatic load and CVD outcomes) was not significantly different for non-Hispanic Black compared to “Non-Hispanic White, Hispanic, Asian, Native American, Native Hawaiian, multiracial and additional racial backgrounds”. The interaction test (difference in the association of high allostatic load and CVD outcomes by race) was not significant for any outcome in either unadjusted or adjusted modeling. (Table 4), as such, race was not a significant moderator of the relationship between allostatic load and composite outcome. In a sensitivity moderation analysis where we restricted the population to examine the difference in association of allostatic load and CVD outcomes between non-Hispanic Black and non-Hispanic White individuals, results were similar in magnitude, significance, and interpretation (Table S6).