Rationale & Objective: Pregnancy complications are risk factors for cardiovascular diseases (CVD). Little is known about the role of renal biomarkers measured shortly after delivery, individually or in combination with pregnancy complications, in predicting subsequent severe maternal CVD. Methods: This study included 576 mothers of multiple ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively. Plasma creatinine and cystatin-C were measured 1-3 days after delivery. CVD during follow-up was defined by physician diagnoses in electronic medical records. Associations of renal biomarkers and pregnancy complications with time-to-CVD events were assessed using Cox proportional hazards models. Results: During an average of 8.2{+/-}2.9 years of follow-up, 33 of 576 mothers developed one or more CVD. Although no associations were found between creatinine and risk of CVD, each doubling of cystatin-C was associated with a hazard ratio (HR) of 4.6 (95% CI=1.5 - 14.0) for CVD. A significant synergistic effect was observed between elevated cystatin-C ([≥]75th percentile) and preeclampsia (P for interaction =0.049). Compared to those without preeclampsia and with normal cystatin-C level (<75th percentile), mothers with preeclampsia and elevated cystatin-C had the highest risk of CVD (HR=4.2, 95%CI=1.6-11.2), while mothers with preeclampsia only or with elevated cystatin-C only had no significantly increased CVD risk. Similar synergistic effects for CVD were observed between cystatin-C and preterm delivery. Conclusions: In this sample of US, traditionally underrepresented multi-ethnic high-risk mothers, maternal plasma cystatin-C and pregnancy complications synergistically increased risk of CVD later in life. These findings warrant further investigation.

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Joint associations of pregnancy complications and postpartum maternal renal biomarkers with severe cardiovascular morbidities: A US racially diverse prospective birth cohort study

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Joint associations of pregnancy complications and postpartum maternal renal biomarkers with severe cardiovascular morbidities: A US racially diverse prospective birth cohort study