Association between aspirin use before 16 weeks of gestation and early postpartum cardiometabolic risk: an electronic health record–based study

Background Preeclampsia (PE) is recognized as a risk-enhancing factor for cardiovascular disease (CVD). Current guidelines recommend that pregnant women at high risk of PE start low-dose aspirin before 16 weeks of gestation to prevent PE. However, whether this early intervention confers early protective effects on postpartum cardiometabolic risk health remains poorly understood. Purpose We aimed to evaluate the association between early pregnancy aspirin use and early postpartum cardiometabolic risk. Methods This study leveraged the Tianjin Health and Medical Data Platform (2014–2023) to identify pregnancies with singleton live births and clinical risk factors for PE. The exposure was defined as receiving an aspirin prescription from an obstetrics/gynecology department before 16 weeks of gestation. Using 1:10 age-matching (±1 year), 2,822 aspirin users were compared with 28,220 non-users. Multivariable Cox proportional hazards models estimated the association between early-pregnancy aspirin use and the risk of postpartum stage 4 cardiovascular-kidney-metabolic (CKM) syndrome and cardiometabolic morbidity. Mediation analyses quantified the proportion of these associations mediated by each adverse pregnancy outcome, adjusted for demographics and baseline risk-factor levels. Results Among the 31,042 pregnant women, the mean age was 31.1 years. Aspirin use was associated with a lower incidence of PE (odds ratio [OR]: 0.73, 95% confidence interval [CI]: 0.61–0.88) and preterm birth (OR: 0.84, 95%CI: 0.67–0.99). Over a median 5-year follow-up, stage 4 CKM syndrome occurred in 117 aspirin users (4.1%) and 1,479 non-users (5.2%). Multivariable Cox models indicated that early aspirin use was associated with a significantly lower risk of Stage 4 CKM syndrome (hazard ratio [HR]: 0.80, 95%CI: 0.64–0.99) and composite CVD outcome (HR: 0.65, 95%CI: 0.49–0.87). No significant associations were observed for incident chronic kidney disease or cardiometabolic morbidity. Mediation analyses indicated that PE mediated a small proportion of the association between early aspirin use and incident Stage 4 CKM syndrome (3.2% [2.3%–8.5%]) and did not significantly mediate associations with incident composite CVD outcome. Conclusions Using real-world electronic health record data, we found that early-pregnancy aspirin use for PE prevention was associated with a lower risk of stage 4 CKM syndrome and CVD over a 5-year postpartum period. The observation that this protection persists largely independent of the occurrence of clinical pregnancy complications highlights the first trimester as a critical therapeutic window for modifying a woman’s lifetime cardiometabolic trajectory. These findings highlight the potential of aspirin as a primary prevention strategy beyond immediate peripartum safety.