Cardiometabolic comorbidity clustering and peripartum cardiovascular risk in rheumatoid arthritis
A Bolad, M Elganainy, I Motairek, F Alenezi, I BoladAbstract
Background
Rheumatoid arthritis (RA) is an independent risk factor for adverse peripartum cardiovascular outcomes, driven by chronic systemic inflammation, accelerated atherogenesis, and immune-mediated endothelial dysfunction. Pregnant individuals with RA face elevated rates of preeclampsia, peripartum cardiomyopathy (PPCM), and severe maternal morbidity compared to the general obstetric population. Cardiometabolic comorbidities such as gestational diabetes (GDM) and chronic hypertension (cHTN) are increasingly prevalent in reproductive-age women and share overlapping pathophysiologic pathways with RA-related vascular injury. Whether their co-occurrence within an RA pregnancy confers synergistic cardiovascular risk beyond individual contributions remains uninvestigated.
Purpose
To determine whether GDM and cHTN cluster synergistically to amplify peripartum cardiovascular risk among delivery hospitalizations complicated by RA.
Methods
Using the 2016-2022 National Inpatient Sample (NIS) databases, we identified delivery hospitalizations with RA using ICD-10-CM codes (n=7,665 unweighted; ~38,325 nationally weighted). Four cardiometabolic exposure groups were defined: neither (84.4%), GDM only (8.5%), cHTN only (6.1%), and both GDM+cHTN (0.9%). Primary outcome: preeclampsia/eclampsia. Secondary outcomes: PPCM, AKI, arrhythmia, heart failure, stroke, VTE, LOS, and charges. Survey-weighted logistic regression adjusting for confounders and comorbidities was performed. Multiplicative and additive (RERI) interaction between GDM and cHTN was assessed.
Results
cHTN alone was the dominant risk factor for preeclampsia (aOR 2.06, 95%CI 1.58–2.69), AKI (aOR 2.49), and heart failure (aOR 11.6). A statistically significant negative multiplicative interaction for preeclampsia was observed (GDM×cHTN interaction OR 0.38, p=0.018), with a significantly negative RERI (−1.34, 95%CI −2.28 to −0.40, p=0.005), indicating sub-additive rather than synergistic risk. The "Both" cluster conferred the highest unadjusted PPCM odds (OR 45.6, p=0.002) and the longest LOS (6.2 days vs. 2.9 days). Preeclampsia rates increased significantly from 7.1% (2016) to 10.6% (2022, p=0.003).
Conclusion
In RA deliveries, cHTN is the primary driver of preeclampsia and heart failure, while combined GDM+cHTN clustering paradoxically fails to amplify preeclampsia risk beyond cHTN alone; possibly reflecting competing pathophysiologic pathways or aggressive antenatal surveillance in this high-risk phenotype. The large PPCM signal in the combined cluster highlights a need for heightened myocardial vigilance in RA patients with dual cardiometabolic burden, directly relevant to emerging cardio-obstetrics frameworks prioritizing risk stratification in autoimmune pregnancy.