Association between adverse pregnancy outcomes and incidence of advanced cardiovascular-kidney-metabolic disease: a population-based cohort study

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Objective: Adverse pregnancy outcomes (APOs) are independent risk factors for cardiovascular disease in women. Within the novel cardiovascular-kidney-metabolic (CKM) framework, evidence linking APOs to advanced CKM (stages 3-4) remains limited. Methods: This study used data from the Kailuan Cohort and combined cross-sectional and longitudinal designs. The cross-sectional analysis included 2,738 women with singleton deliveries. For the longitudinal analysis, 2,575 women without advanced CKM at baseline were followed up for a median of 11.68 years. A history of APOs was the primary exposure. Multinomial logistic regression and Cox proportional hazards models were used. Results: Cross-sectionally, APOs were positively associated with baseline CKM stage severity, with odds ratios increasing across stages (Stage 1: odds ratio [OR] 1.42, 95% confidence interval [CI] 1.03-1.96; Stage 2: OR 1.65, 95% CI 1.26-2.17; advanced CKM: OR 2.93, 95% CI 1.74-4.94). Women with APOs had a higher incidence of advanced CKM than those without (13.39 vs. 8.42 per 1,000 person-years). After multivariable adjustment, a history of APOs was associated with a 27% increased risk of incident advanced CKM (hazard ratio 1.27, 95% CI 1.01-1.61). Sensitivity analyses excluding participants with less than 4 years of follow-up and those taking medications at baseline yielded results consistent with the primary analysis. In the exploratory analyses, we further evaluated the association between a history of APOs and incident CKM stages 3 and 4. A history of APOs was associated with an increased risk of incident CKM Stage 4, whereas no statistically significant association was observed with incident CKM Stage 3. Conclusion: A history of APOs was associated with greater baseline CKM severity and an increased risk of developing advanced CKM. Therefore, APOs may serve as early markers for identifying women at risk of progressive CKM.

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