A new study published in the Journal of the American Heart Association examines the association between a woman’s obstetric history by age 40 and her risk of fatal ischemic heart disease related to atherosclerosis.

Study: Pregnancy history at 40 years of age as a marker of cardiovascular risk. Image Credit: Africa Studio / Shutterstock.com

Pregnancy and cardiovascular health

Cardiovascular disease (CVD) is the most common cause of death among women. However, CVD is less likely to be identified or treated in women as compared to men.

Atherosclerotic cardiovascular disease (ASCVD) is twice as common in women who have experienced one or more complicated pregnancies. This could be due to increased pressure on the heart and vascular system during pregnancy. This association between pregnancy complications and future CVD risk has led many physicians to include pregnancy history while assessing CVD risk in women.

The Nurses’ Health Study reported an increase in the rate of both fatal and nonfatal cardiovascular events among women with two or more hypertensive pregnancies as compared to those without this medical history. The number of growth-restricted pregnancies was also linked to these events in a Swedish study. Similar results have been reported from other research as well, thus indicating that greater parity increases the risk of a greater number of complicated pregnancies.

About the study

The current study included data from Norwegian registries between 1967 to 2020. The study cohort comprised over 850,000 participants, all of whom were born within the last 70 years from the start of the study or were pregnant at some point from 1967 onwards and reached at least the age of 40 years, as this is the age at which reproductive function is completed in 97% of women.

The study aimed to determine how long these women lived until they died of ASCVD at the beginning of the study when they would have been 69 years or younger. This was correlated with the number of recorded pregnancies for each woman and included both stillbirths and live births.

Women who likely could not have had more than one birth during this period and those with prolonged but uncomplicated pregnancies and unlikely birth weights were not included to ensure high data quality.  

The scientists recorded the number of complicated pregnancies, with respect to preterm delivery before35 weeks of gestation, pre-eclampsia, abruption of the placenta, perinatal death, which occurred shortly before, during, or after childbirth, and birth weight below 2.7 kg for babies born near or at term.

What did the study show?

Among these women, about 16% had no births, while 14% had a single pregnancy. About 40% and 20% had two and three pregnancies, respectively, while women with 4% of the study cohort had four pregnancies. Complicated pregnancies were recorded in 16% of parous women.

Less than 0.25% of women died of ASCVD by the age of 69 years. However, the rate of death showed wide variations depending on the pregnancy history.

More specifically, women with a history of 3threepregnancies without any complications had the lowest mortality due to ASCVD. Comparatively, women without a history of pregnancy were at a four-fold risk of death from ASCVD, while one uncomplicated pregnancy was associated with a two-fold higher risk. Those with two or more complicated pregnancies by the time they were 40 were at up to a five-fold higher risk of dying from ASCVD.

The risk of dying from ASCVD rose for those 69 years from birth, in proportion to the number of complicated pregnancies. This increase was obviously related to the number of exposures. Women with four complicated pregnancies were at a 24-fold increased risk of ASCVD-related mortality as compared to the reference group.

This single parameter predicted an increase in the risk of death from ASCVD by 2.5 to five-fold among 20% of women who were alive at the age of 40 years. About 57% were considered to have a relatively favorable risk for ASCVD mortality risk at less than 1.5 the reference group risk. Conversely, 0.3% were at a severe risk at over five-fold.

What are the implications?

A strong association was observed between the pregnancy history of a woman by the age of 40 and future ASCVD-related death risk. Moreover, the significance of a full pregnancy history is exposed, as the number of complicated pregnancies out of the total number of pregnancies is as important as the total number of complications. According to the authors, having two complicated pregnancies out of two total pregnancies confers a much greater risk as compared to two out of four.

The increased risk might be due to shared factors underlying both pregnancy complications and CVD, such as inflammation, abnormal blood lipid profiles, endothelial dysfunction, or metabolic syndrome. Furthermore, women with a history of one complicated pregnancy are at an increased risk of future complicated pregnancies but with a different complication, thus suggesting that these complications have common origins.

An important question is the extent to which a woman’s pregnancy history at 40 years of age predicts CVD risk beyond that due to overt pathologies such as diabetes, obesity, or hypertension.”

Additional research is needed to understand how the findings of this study will enhance risk prediction of cardiovascular death beyond the known risk factors.