Dr Duzyj Buniak is Assistant Professor, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Rutgers Robert Wood Johnson School of Medicine, New Brunswick, New Jersey.
Dr Louis is Assistant Professor, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Morsani College of Medicine and Department of Community and Family Health, College of Public Health, University of South Florida, Tampa.
Neither author has a conflict of interest to report with respect to the content of this article.
It is not news that cardiovascular disease (CVD) is the number-one cause of death among women, accounting for 22.9% of all deaths.1 Yet only 1 in 5 women believe that heart d isease is their greatest risk, and this despite the mortality data and the American Heart Association’s (AHA) “Go Red for Women” campaign, which has been around for 12 years.2 What is becoming increasingly newsworthy in an abundance of literature is that a woman’s response to pregnancy appears to predict her later cardiovascular health.3-6
Previously developed scoring and risk algorithms for CVD may underestimate the risk in reproductive-age women because they focus primarily on obesity and metabolic syndrome, hypertension, diabetes, and family history.7 In 2011, the AHA recommended including a woman’s obstetric history in risk assessment, in its updated report, “Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women.”8
In 2014, the organization took it a step further with its “Guidelines for the Prevention of Stroke in Women,” which included history of preeclampsia and gestational hypertension in the risk profile for CVD.9 For the first time, non-obstetricians were being encouraged to ask women about their obstetric history and to consider the existing evidence about the long-term implications of pregnancy-related complications.
Obstetricians are well-versed in counseling patients about pregnancy complications such as preeclampsia, gestational diabetes, stillbirth, and preterm birth (PTB) that may recur or predispose to another major obstetric complication in future pregnancies.10-13 We have been less adroit, however, at describing what these outcomes mean for future maternal health. A significant body of emerging data indicates a clear association between adverse pregnancy outcomes and future maternal CVD (Table 1).
Epidemiologic studies from the Netherlands demonstrated that women who experienced severe preeclampsia had a 7.58 (7.05–8.14)-fold increased risk of developing chronic hypertension in an average of 14 years of follow-up after the index pregnancy relative to women with uncomplicated pregnancies.14
The risk of developing clinical hypertension by age 50 thus increases from 5% among women with healthy pregnancies to 20% in those with a history of severe preeclampsia. In women with severe preeclampsia, the odds of all associated CV complications—including ischemic heart disease (odds ratio [OR] 2.11; 1.76–2.52), stroke (OR 1.61; 1.35–1.93), thromboembolism (OR 2.18; 1.70–2.80), and type II diabetes (OR 4.09; 3.52–4.76)—are statistically higher. The result is an increase in death from all causes (OR 1.38; 1.11–1.71) in women at a mean follow-up age of 41.6 years.
The time to manifestation of CVD is not trivial. Follow-up of women in the Hypertension and Pre-eclampsia Intervention Trial at near Term (HYPITAT) study demonstrated elevated clinical and laboratory features of cardiometabolic disease at only 2.5 years following a pregnancy with hypertensive complications.15 The association between dyslipidemia, preeclampsia, and subsequent development of ischemic heart disease has also been scrutinized. Prepregnancy CVD risk factors such as abnormal lipid profiles may contribute to the development of preeclampsia in addition to future CVD risk.16
The association between pregnancy-related complications and future morbidity and mortality is not limited to pregnancy-related hypertension. A different study of the Dutch cohort demonstrated a higher rate of death due to CVD in women who had PTB (OR 1.98; 95% CI 1.64–2.40), stillbirth (1.80; 95% CI 1.06–3.01), or small-for-gestational-age infants (OR 2.56; 95% CI 2.19–3.00).17,18
A recent review demonstrated that women with any history of PTB had an increased risk of cardiovascular morbidity (adjusted hazard ratio [aHR] 1.2–2.9), ischemic heart disease (1.3–2.1), stroke (1.7), and atherosclerosis (4.1).18 The association between in-hospital death and PTB was higher with elective PTB (defined as induced delivery without onset of labor) (aHR, 1.8; 95% CI, 1.6–2.0) than with spontaneous PTB (defined as vaginal delivery without induction or cesarean delivery after onset of labor) (aHR, 1.5; 95% CI, 1.3–1.6).19
Taken together, this suggests that any adverse pregnancy outcome can have long-term implications for a woman’s health.
The biological mechanism
The scientific underpinnings of these associations likely are multifactorial and related to the challenges of early pregnancy implantation and establishment at the level of the individual blood vessel. Women with baseline obesity and/or metabolic syndrome are known to carry an additional risk of adverse outcome in pregnancy, most likely related to underlying vascular disease and atherosclerosis.20,21
However in otherwise healthy-appearing women, scientific literature supports an array of biochemical mechanisms which may weaken the maternal uterine blood vessels and contribute to poor quality of the placental vascular connection between mother and baby. These mechanisms include a genetic predisposition to altered vascular tone and responsiveness, an immune maladaptation/impedance to placental cell invasion into maternal compartments, placental extravillous trophoblast cell inability to access the maternal endovascular compartment for normal vascular remodeling, a baseline subclinical endothelial dysfunction, or imbalance in the maternal thrombostatic system causing alterations in blood flow.22-26
Individually or collectively these may contribute to adverse pregnancy outcome. The normal processes of pregnancy, then, are unmasking a larger maternal vascular predisposition that is likely to manifest again with stressors later in life.27
Implications for clinical care
Interventions may help prevent or delay the onset of CVD in at-risk women. The American College of Obstetricians and Gynecologists now recommends that “for women with a medical history of preeclampsia who gave birth preterm (less than 37 0/7 weeks of gestation) or who have a medical history of recurrent preeclampsia, a yearly assessment of blood pressure, lipids, fasting blood glucose, and body mass index should occur.”28 More aggressively, current AHA guidelines indicate that women with risk factors, which now include pregnancy-related outcomes, should be referred for preventive management.4
No evidence-based strategies exist for postpartum women, but interventions used for reproductive-age women are recommended. Such strategies focus first on lifestyle interventions, given the reproductive risks of some therapeutic agents, such as lipid-lowering drugs.4
A review of data from clinical trials indicates that among women of reproductive age, lifestyle interventions including diet, exercise, and smoking cessation have modest effects on lowering lipids and systolic blood pressure. The effects of exercise are more pronounced with an increased dose.29 Intervention strategies are then heightened for women who are considered high-risk for CVD, including those with diabetes.4
Once providers recognize the long-term risk associated with adverse pregnancy outcomes, they still face barriers in patient identification, management, and access to care. One Canadian study focused on expanded postpartum visits with an interdisciplinary transition to primary care for ensuring that the appropriate groundwork was laid.30 The most common reasons for referral were gestational diabetes (32.7%), preeclampsia (29.3%), PTB (29.3%), or gestational hypertension (19.6%). In their 6- to 12-month postpartum assessment, women whose pregnancies were complicated by preeclampsia were more likely to have postpartum weight retention of ≥10 kg (18 vs 9%, P <.05), metabolic syndrome (17.4 vs 6.8%, P <.001), and 2 or more major risk factors for CVD (9.8 vs 0.7%, P <.001) than were controls.
Women in the clinic analysis group had significantly increased lifetime and 30-year CVD risk estimates compared with healthy controls
(P < .0001). The authors concluded that referring women in this manner for primary care appropriately targeted at-risk women for further prevention.
But appropriate referral is not the entire story. Another barrier is highlighted by a prospective study of women whose pregnancies were complicated by gestational diabetes and hypertensive disorders.31 Among the 176 women who presented for a 3-month postpartum visit, 57.9% of those with gestational diabetes had completed glucose testing, 97.9% with hypertensive disease of pregnancy had blood-pressure testing, and only 57.4% with either diagnosis recalled having lipid screening, despite 96% attendance at their 6-week postpartum visit.31
The women least likely to complete screening tests were those who had no college education, less than a high-school level of health literacy, and who were not privately insured.31 These findings suggest the need for a 2-pronged approach: education for the women affected as well as for their providers, to ensure thorough care and adherence to current practice guidelines.
Counseling for women who experience pregnancy-related complications including preeclampsia, gestational diabetes, stillbirth, and PTB should reflect this new understanding of disease across the lifespan.
Common sense suggests that during the postpartum visit, physicians should educate a woman about her future risk, emphasize lifestyle interventions (especially loss of pregnancy weight via healthy diet and exercise), and establish an appropriate timeframe for primary care follow-up depending on the pregnancy outcome. This intervention may benefit future pregnancies as well as long-term cardiovascular health.
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The AHA serially releases guidelines outlining targets for risk reduction, and these may be the best we can offer our patients: total cholesterol <200 mg/dL, BP < 120/80, BMI < 25 kg/m2, fasting glucose < 100 mg/dL, healthy diet, moderate exercise (> 150 min/week), and no tobacco use.4
In order to best serve women who are at risk because of their obstetric histories, research gaps need to be addressed. Initial studies have demonstrated that we can target and properly identify at-risk women in the postpartum period but intervention studies are lacking. Potential short-term gains from these interventions would include decreased maternal and neonatal morbidity for subsequent pregnancies. The long-term goal would be demonstration of decreased CVD burden among these women through primary and secondary prevention.
As doctors for women, we have an opportunity and responsibility to educate our patients about their future health. We have access to pregnancy-related information that can help primary care providers in their risk algorithms for monitoring health. As such, we need to develop a new paradigm for viewing pregnancy as a part of a woman’s lifelong health, and develop strategies for optimizing care to benefit long-term outcomes. ï¼
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