Major adverse pregnancy outcomes confer long-term ischemic heart disease risk in women
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Women who had any of five major adverse pregnancy outcomes had elevated risk for ischemic heart disease for as long as 46 years after delivery, researchers reported in The BMJ.
“Remarkably, we found that all of them were independent long-term risk factors for ischemic heart disease, even out to 46 years of follow-up,” Casey Crump, MD, PhD, vice chair for research in the department of family medicine and community health and professor of epidemiology in the department of population health science and policy at Icahn School of Medicine at Mount Sinai, told Healio. “These are essentially lifelong risk factors for heart disease in women.”
Data were derived from Crump C, et al. BMJ. 2023;doi:10.1136/bmj-2022-072112.
In an analysis of 2,195,266 Swedish women who had a first singleton delivery between 1973 and 2015, Crump and colleagues determined whether there were any associations between long-term risk for ischemic heart disease in women and any of five major adverse pregnancy outcomes: preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders of pregnancy and gestational diabetes.
“Adverse pregnancy outcomes are extremely common,” Crump told Healio. “Nearly 30% of women have one during their reproductive years. They have often been examined separately and found to be risk factors for cardiovascular disease or its risk factors, but they have rarely been examined in the same cohort, which is helpful for examining risks associated with each of those adverse pregnancy outcomes.”
Ischemic heart disease risk
During the study period of 53.6 million person-years of follow-up, ischemic heart disease was diagnosed in 3.8% of women.
Crump and colleagues found that compared with women who did not have a major adverse pregnancy outcome, women who had the following outcomes were at increased risk for ischemic heart disease at 10 years after delivery:
- other hypertensive disorders of pregnancy (adjusted HR = 2.09; 95% CI, 1.77-2.46);
- preterm delivery (aHR = 1.72; 95% CI, 1.55-1.9);
- preeclampsia (aHR = 1.54; 95% CI, 1.37-1.72);
- gestational diabetes (aHR = 1.3; 95% CI, 1.09-1.56); and
- small for gestational age (aHR = 1.1; 95% CI, 1-1.21).
Crump and colleagues wrote that the risk remained elevated at 30 to 46 years after delivery:
- other hypertensive disorders of pregnancy (aHR = 1.47; 95% CI, 1.3-1.66);
- gestational diabetes (aHR = 1.4; 95% CI, 1.29-1.51);
- preeclampsia (aHR = 1.32; 95% CI, 1.28-1.36);
- preterm delivery (aHR = 1.23; 95% CI, 1.19-1.27); and
- small for gestational age (aHR = 1.16; 95% CI, 1.13-1.19).
In co-sibling analyses, shared familial genetic and environmental factors only partially (< 45%) explained the findings, the researchers wrote.
The risk for ischemic heart disease was greater in women with more than one major adverse pregnancy outcome, Crump and colleagues wrote, citing as an example that at less than 10 years, the aHR for women with one major adverse pregnancy outcome was 1.29 (95% CI, 1.19-1.39) compared with 1.8 (95% CI, 1.59-2.03) for women with two adverse outcomes and 2.26 (95% CI, 1.89-2.7) for women with three adverse outcomes.
More aggressive screening, treatment
“Adverse pregnancy outcomes are an early signal for future heart disease risk, and they can help identify high-risk women much earlier, and thus enable earlier preventive actions to improve their long-term outcomes,” Crump told Healio. “Those women need more aggressive reduction of other cardiovascular risk factors like obesity, physical inactivity and smoking, and this needs to be implemented as early as possible, with long-term follow-up by their physicians.”
In addition, Crump said, “These women need more aggressive screening for and reduction of unhealthy lifestyle factors as well as hypertension, diabetes and high cholesterol. They need to have these interventions as early as possible to help prevent the development of heart disease and to improve their long-term outcomes. What is most exciting about this study is that it will help us identify these women earlier so we can intervene earlier and therefore improve their outcomes across their life.”
For more information:
Casey Crump, MD, PhD, can be reached at casey.crump@mssm.edu.
Perspective
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Anais Hausvater, MD
This is an important study because it is the largest prospective study to look at the long-term risk for ischemic heart disease (MI or angina) related to adverse pregnancy outcomes (APO) including preterm delivery, delivery of infants that are small for gestational age, high BP syndromes of pregnancy (like preeclampsia or gestational hypertension) or gestational diabetes. This study is unique because it collects data on APOs from birth records and follows women for up to 46 years. Prior studies of CVD after adverse pregnancy outcomes have relied on maternal recall, which is less reliable, particularly when more than 10 years have passed since pregnancy. Some important take-home messages:
- Over 2 million women were included in this study. APOs were common: about one-third of women experienced at least one adverse pregnancy. The most common was delivery of small-for-gestational-age infant.
- Only 4% of women experienced ischemic heart disease, the majority of which were MIs or ischemic chest pain.
- All five APOs were associated with increased risk for ischemic heart disease even after considering other risk factors like age, diabetes, high BP, etc.
- When the heart disease occurred closer to delivery (< 10 years), the risk was highest (more than doubled) after high BP during pregnancy. This means it is essential we focus on preventative measures early after pregnancy among these women.
- Risk remained elevated over time (up to 46 years after pregnancy). This means that complications of pregnancy increases risk for heart disease even up to nearly 50 years postpartum. So, this risk factor is lifelong.
- Over the whole follow-up period, preeclampsia and gestational diabetes were associated with the most excess risk for heart disease.
- The authors did an analysis of siblings to account for any effects of genetics and early-life environmental factors which might influence the relationship between APOs and future heart disease. They found there was only a partial influence of genetics and early life environmental factors on the risk for heart disease after any APO. This means that something other than genetics, early life factors, age and underlying conditions is driving this increased risk, and more studies are needed to understand what the mechanisms are.
- Women who experienced multiple APOs had the highest risk for ischemic heart disease.
- This study highlights how important it is that women who have experienced an adverse pregnancy outcome should be followed up with a primary care doctor or a cardiologist early after pregnancy to assess their risk for heart disease.
- If a woman has had an adverse pregnancy outcome in the past (even if it happened a very long time ago), she should make sure to mention it at her next doctor’s appointment, so this risk factor is being considered.
- The best thing we can do to prevent future ischemic heart disease is to optimize CV health early. This means: check cholesterol levels and make sure they are at target (some women might need treatment with medications for very high cholesterol), control BP (goal < 130 mm Hg systolic/< 80 mm Hg diastolic), aim for a BMI < 25 kg/m2 within 1 year postpartum, exercise (~150 minutes per week), quit smoking, screen for and treat diabetes, eat a healthy diet (Mediterranean plant-based style diet) and ensure adequate sleep (~7.5 to 8 hours per night).
- Women who have already had one APO and are planning a subsequent pregnancy should talk to their doctor about baby aspirin for prevention.
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