Association of Adverse Pregnancy Outcomes With Risk of Atherosclerotic Cardiovascular Disease in Postmenopausal Women

Abstract

Importance: Atherosclerotic cardiovascular disease (ASCVD) may have unique risk factors in women. Most women have a history of pregnancy; common adverse pregnancy outcomes (APOs) appear to be associated with ASCVD, but prior studies have limitations.

Objective: To assess whether APOs are associated with increased ASCVD risk independently of traditional risk factors.

Design, setting, and participants: The APO history among participants in the Women's Health Initiative, a large multiethnic cohort of postmenopausal women, was assessed. The associations of 5 self-reported APOs (gestational diabetes, hypertensive disorders of pregnancy, low birth weight [ie, birth weight less than 2.49 kg], high birth weight [ie, birth weight greater than 4.08 kg], and preterm delivery by 3 weeks or more) with ASCVD were analyzed, adjusting for traditional ASCVD risk factors. Data were collected and analyzed in 2017.

Exposures: APOs (gestational diabetes, hypertensive disorders of pregnancy, low birth weight, high birth weight, and preterm delivery).

Main outcomes and measures: Adjudicated ASCVD.

Results: A total of 48 113 Women's Health Initiative participants responded to the survey; the median (interquartile range) age at time of enrollment was 60.0 (55.0-64.0) years. A total of 13 482 participants (28.8%) reported 1 or more APOs. Atherosclerotic cardiovascular disease was more frequent in women who reported an APO compared with those without APOs (1028 of 13 482 [7.6%] vs 1758 of 30 522 [5.8%]). Each APO, analyzed separately, was significantly associated with ASCVD, and gestational diabetes, hypertensive disorders of pregnancy, low birth weight, and preterm delivery remained significant after adjustment for traditional ASCVD risk factors. When all APOs were analyzed together, hypertensive disorders of pregnancy (odds ratio, 1.27; 95% CI, 1.15-1.40) and low birth weight (odds ratio, 1.12; 95% CI, 1.00-1.26) remained independently associated with ASCVD. All findings were materially unchanged by additional adjustment for parity, body mass index, and socioeconomic factors.

Conclusions and relevance: In this large multiethnic cohort of women, hypertensive disorders of pregnancy and low birth weight were independently associated with ASCVD after adjustment for risk factors and other APOs.

Figure 1.. Flow Diagram for the Selection of the Study Participants From the Women’s Health Initiative (WHI)

Figure 2.. Association of Individual Adverse Pregnancy Outcomes (APOs) With Atherosclerotic Cardiovascular Disease (ASCVD)

Each line displays the odds ratio and its 95% CI from the comparison of yes and no responses based on a multinomial logistic model. For each APO, the top line shows the odds ratio for the APO from an unadjusted model and the bottom line shows the odds ratio for the APO from a model that adjusted for all traditional ASCVD risk factors, including age, hyperlipidemia, hypertension, diabetes, and smoking.

Figure 3.. Association of Multiple Adverse Pregnancy Outcomes (APOs) With Atherosclerotic Cardiovascular Disease (ASCVD)

Each line displays the odds ratio and it 95% CI from the comparison of yes and no responses based on a multinomial logistic regression model. For each APO, the top line shows the odds ratio adjusted for traditional ASCVD risk factors, including age, hyperlipidemia, hypertension, diabetes, and smoking, but for no other APOs. The next 4 lines show the odds ratio adjusted for the traditional ASCVD risk factors plus an additional APO. The bottom line shows the odds ratio for the APO adjusted for the traditional ASCVD risk factors plus all other 4 APOs.