Pregnancy History at 40 Years of Age as a Marker of Cardiovascular Risk

Abstract

Background Individual pregnancy complications are associated with increased maternal risk of cardiovascular disease. We assessed the link between a woman's total pregnancy history at 40 years of age and her relative risk of dying from atherosclerotic cardiovascular disease (ASCVD). Methods and Results This population‐based prospective study combined several Norwegian registries covering the period 1967 to 2020. We identified 854 442 women born after 1944 or registered with a pregnancy in 1967 or later, and surviving to 40 years of age. The main outcome was the time to ASCVD mortality through age 69 years. The exposure was a woman's number of recorded pregnancies (0, 1, 2, 3, or 4) and the number of those with complications (preterm delivery <35 gestational weeks, preeclampsia, placental abruption, perinatal death, and term or near‐term birth weight <2700 g). Cox models provided estimates of hazard ratios across exposure categories. The group with the lowest ASCVD mortality was that with 3 pregnancies and no complications, which served as the reference group. Among women reaching 40 years of age, risk of ASCVD mortality through 69 years of age increased with the number of complicated pregnancies in a strong dose–response fashion, reaching 23‐fold increased risk (95% CI, 10–51) for women with 4 complicated pregnancies. Based on pregnancy history alone, 19% of women at 40 years of age (including nulliparous women) had an increased ASCVD mortality risk in the range of 2.5‐ to 5‐fold. Conclusions Pregnancy history at 40 years of age is strongly associated with ASCVD mortality. Further research should explore how much pregnancy history at 40 years of age adds to established cardiovascular disease risk factors in predicting cardiovascular disease mortality.

Count From Zero: Pregnancy History and Heart Risk

“…Therefore, the investigation by Kvalvik et al 5 in this issue of the Journal of the American Heart Association ( JAHA ) is an important contribution on the relationship of pregnancy history, APOs, and future cardiovascular events. The aim of this population‐based, prospective study was to determine the association between a woman's complete pregnancy history (defined as total number of pregnancies and number of complicated pregnancies at 40 years old) and risk of death from atherosclerotic CVD (ASCVD) between the ages of 40 and 69 years.…”

“…Kvalvik et al 5 demonstrated that, compared with women at the age of 40 years with 3 uncomplicated pregnancies (reference), an increased risk for ASCVD death was noted in nulliparous women (hazard ratio [HR], 2.9 [95% CI, 2.4–3.4]) and women with a single uncomplicated pregnancy (HR, 2.2 [95% CI, 1.9–2.7]). However, at each parity, the trajectory for risk of ASCVD death significantly increased with each number of complicated pregnancies.…”

“…Some limitations of the study by Kvalvik et al 5 reflect challenges when analyzing registry data. Gestational diabetes, an APO with a strong association of developing future diabetes and CVD events, 9 was not consistently recorded in the Norwegian birth registry and was excluded from analysis.…”

“…Sample sizes in higher‐risk groups were smaller, and insufficient data were available to separately analyze nulliparous versus nulligravida women. The analysis by Kvalvik et al 5 was not adjusted for multiple traditional risk factors. However, the Women's Health Initiative (n=46 805; median, 60.0 [interquartile range, 55.0–64.0] years old) demonstrated that APOs are associated with increased ASCVD risk independent of traditional risk factors, including hyperlipidemia, hypertension, diabetes (not gestational), smoking status, income, education, and race and ethnicity.…”

JAHA Go Red for Women Spotlight on Women and Cardiovascular Disease and Stroke

“…Another study by Kvalvik et al examined the number of pregnancies and the complications associations with each pregnancy among a Norwegian population‐based prospective study following women from 1967 to 2020. 9 They found that at 40 years of age, the risk of atherosclerotic cardiovascular disease death increased with the number of complicated pregnancies in a dose–response manner, and women with ≥4 pregnancy complications had a 23‐fold increase in adverse outcomes. The accompanying editorial by Johnson highlights the need for future research on effective strategies to mitigate the impact of pregnancy factors, especially in more racially and ethnically diverse populations.…”