DISCUSSION:
In this prospective cohort study, high allostatic load in early pregnancy was associated with subsequent composite outcome 2 to 7 years after delivery. After adjustment for covariates, high allostatic load was significantly associated with composite outcome, HTN, and MD. Results were similar in sensitivity analysis, where we adjusted for prior APOs. The components of allostatic load most strongly associated with CVD outcomes in exploratory analyses were BMI, SBP, DBP, and CRP. These data support growing evidence that cumulative stress is associated with subsequent CVD-related outcomes.
Others also have noted allostatic load as a risk factor for increased risk of contemporaneous coronary artery disease, ischemic heart disease, and peripheral arterial disease. 24-27 Similarly, individuals with type 2 diabetes, elevated blood pressure and worse glycemic control have higher allostatic load. 24-27Again, these studies assessed contemporaneous allostatic load.33
Generally, subclinical higher levels of blood pressure and glucose metabolism are associated with subsequent HTN and MD.28 As such blood pressure and metabolic parameters were individually associated with subsequent CVD and high allostatic load remained significantly associated with subsequent CVD, even when we excluded blood pressure and insulin from the allostatic load index for the composite, HTN and MD.
Self-reported race has been included as a proxy for social experience, systematic and interpersonal racism, and other unmeasured social determinants of health. As such allostatic load has been strongly associated with the non-Hispanic Black race in several studies.29, 30 Black individuals reporting greater perceived racial discrimination had a higher allostatic load. 31However, one study noted that this was somewhat mitigated by additional educational attainment. 32 We found that non-Hispanic Black race was associated with high allostatic load and CVD outcomes. The addition of allostatic load only partially mediated the relationship between race and CVD outcomes in our study and not between race and each component of the composite outcome as such these associations were not significantly different by race.
Our study has several limitations. Our cohort lacks some generalizability since it was limited to nulliparous individuals who could access tertiary medical care centers and had the means to participate in a complex longitudinal study. This analysis was restricted to individuals in a follow-up study, introducing potential bias in the cohort. Also, we only evaluated allostatic load during the first trimester of the index pregnancy. Thus, we could not assess the trajectory relationship between allostatic load later in pregnancy or allostatic load and CVD outcomes longitudinally. Also, we could not assess the impact of subsequent pregnancies between the index pregnancy and HHS in person visit 2-7 years postpartum. Although we assessed a 12-factor index and individual components of allostatic load, we did not assess other combination, including additional metabolic and cardiovascular indicators that make up a broader allostatic load index, which may be more robust for evaluating allostatic load and CVD.33
This study had notable strengths. We utilized a large, well-characterized prospective cohort with standardized data collection by trained research personnel. Outcomes used rigorous definitions, and physicians adjudicated uncertain cases. 11Importantly, our population was geographically, racially, and ethnically diverse and is somewhat representative of the US population. Another strength is that each allostatic load biomarker component was weighted equally, a scientifically sound approach. Evidence suggests no significant difference between empirical and clinical cut-off assessments. 34
In summary, early pregnancy high allostatic load is associated with composite maternal CVD outcomes 2-7 years postpartum, particularly HTN and MD. High allostatic load early in pregnancy could indicate increased risk for subsequent HTN and MD. High allostatic load modestly mediated the association between self-reported race and composite outcome, but not individual components of the composite outcome. Discovery of early pregnancy biomarkers that are associated with increase long-term CVD risk might have impact on public health. Thus, pathways contributing to allostatic load such as stress and inflammation should be investigated as therapeutic targets intended to decrease CVD.