Joint Associations of Pregnancy Complications and Postpartum Maternal Renal Biomarkers With Severe Cardiovascular Morbidities: A US Racially and Ethnically Diverse Prospective Birth Cohort Study

Author:

Hong Xiumei1ORCID,Rosenberg Avi Z.2ORCID,Heymann Jurgen3ORCID,Yoshida Teruhiko3ORCID,Waikar Sushrut S.4,Ilori Titilayo O.4ORCID,Wang Guoying1ORCID,Rebuck Heather5ORCID,Pearson Colleen6ORCID,Wang Mei‐Cheng7ORCID,Winkler Cheryl A.8,Kopp Jeffrey B.3,Wang Xiaobin19ORCID

Affiliation:

1. Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease Johns Hopkins University Bloomberg School of Public Health Baltimore MD USA

2. Department of Pathology Johns Hopkins University MD Baltimore USA

3. Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health MD Bethesda USA

4. Section of Nephrology, Department of Medicine Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center Boston MA USA

5. Clinical Chemistry Research Lab University of Maryland School of Medicine Baltimore MD USA

6. Department of Pediatrics Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center Boston MA USA

7. Department of Biostatistics Johns Hopkins University Bloomberg School of Public Health Baltimore MD USA

8. Cancer Innovation Laboratory, Center for Cancer Research National Cancer Institute and Basic Research Program, Frederick National Laboratory Frederick MD USA

9. Division of General Pediatrics & Adolescent Medicine, Department of Pediatrics Johns Hopkins University School of Medicine Baltimore MD USA

Abstract

Background Pregnancy complications are risk factors for cardiovascular disease (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 and Results This study included 566 mothers of diverse races and ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively. Plasma creatinine and CysC (cystatin C) were measured 1 to 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. During an average of 10.3±3.2 years of follow‐up, 30 mothers developed 1 or more CVDs. Only a modest association was observed between creatinine and risk of CVD. In comparison, we found that per 0.1 mg/L increase of CysC was associated with a hazard ratio (HR) of 1.2 (95% CI, 1.1–1.4) for CVD after adjusting for covariates. Compared with those without preeclampsia and with normal CysC level (≤75th percentile), mothers with preeclampsia and elevated CysC (>75th percentile) had the highest risk of CVD (HR, 4.6 [95% CI, 1.7–17.7]), whereas mothers with preeclampsia only or with elevated CysC only did not have significantly increased CVD risk. Similar synergistic effects for CVD were observed between CysC and preterm delivery. Conclusions In this sample of US, traditionally underrepresented multiracial and multiethnic high‐risk mothers, elevated maternal plasma CysC, independently and jointly with pregnancy complications, increased risk of CVD later in life. These findings warrant further investigation. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03228875.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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