Prepregnancy plant-based diets and risk of hypertensive disorders of pregnancy.

BACKGROUND: Plant-based diets have been associated with a lower risk of cardiovascular disease in nonpregnant adults, but specific evidence for their effects on risk of hypertensive disorders of pregnancy is scarce. OBJECTIVE: This study aimed to evaluate the prospective association between adherence to plant-based diets before pregnancy and the risk for hypertensive disorders of pregnancy. We hypothesized that women with higher adherence to plant-based diets would have a lower risk for hypertensive disorders of pregnancy. STUDY DESIGN: We followed 11,459 parous women (16,780 singleton pregnancies) without chronic diseases, a history of preeclampsia, and cancers who participated in the Nurses' Health Study II (1991-2009), which was a prospective cohort study. Diet was assessed every 4 years using a validated food frequency questionnaire from which we calculated the plant-based diet index (higher score indicates higher adherence) to evaluate the health associations of plant-based diets among participants while accounting for the quality of plant-based foods. Participants self-reported hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension. We estimated the relative risk of hypertensive disorders of pregnancy in relation to plant-based diet index adherence in quintiles using generalized estimating equations log-binomial regression while adjusting for potential confounders and accounting for repeated pregnancies for the same woman. RESULTS: The mean (standard deviation) age at first in-study pregnancy was 35 (4) years. A total of 1033 cases of hypertensive disorders of pregnancy, including 482 cases of preeclampsia (2.9%) and 551 cases of gestational hypertension (3.3%) were reported. Women in the highest quintile of plant-based diet index were significantly associated with a lower risk for hypertensive disorders of pregnancy than women in the lowest quintile (relative risk, 0.76; 95% confidence interval, 0.62-0.93). There was an inverse dose-response relationship between plant-based diet index and risk for hypertensive disorders of pregnancy. The multivariable-adjusted relative risk (95% confidence interval) of hypertensive disorders of pregnancy for women in increasing quintiles of plant-based diet index were 1 (ref), 0.93 (0.78-1.12), 0.86 (0.72-1.03), 0.84 (0.69-1.03), and 0.76 (0.62-0.93) with a significant linear trend across quintiles (P trend=.005). This association was slightly stronger for gestational hypertension (relative risk, 0.77; 95% confidence interval, 0.60-0.99) than for preeclampsia (relative risk, 0.80; 95% confidence interval, 0.61-1.04). Mediation analysis suggested that body mass index evaluation for dietary assessment and pregnancy explained 39% (95% confidence interval, 15%-70%]) of the relation between plant-based diet index and hypertensive disorders of pregnancy and 48% (95% confidence interval, 12%-86%]) of the relation between plant-based diet index and gestational hypertension. CONCLUSION: Higher adherence to plant-based diets was associated with a lower risk of developing hypertensive disorders of pregnancy. Much of the benefit seems to be related to improved weight control.

Prepregnancy Migraine, Migraine Phenotype, and Risk of Adverse Pregnancy Outcomes.

BACKGROUND AND OBJECTIVE: Migraine is a highly prevalent neurovascular disorder among reproductive-aged women. Whether migraine history and migraine phenotype might serve as clinically useful markers of obstetric risk is not clear. The primary objective of this study was to examine associations of prepregnancy migraine and migraine phenotype with risks of adverse pregnancy outcomes. METHODS: We estimated associations of self-reported physician-diagnosed migraine and migraine phenotype with adverse pregnancy outcomes in the prospective Nurses' Health Study II (1989-2009). Log-binomial and log-Poisson models with generalized estimating equations were used to estimate relative risks (RRs) and 95% CIs for gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension, preterm delivery, and low birthweight. RESULTS: The analysis included 30,555 incident pregnancies after cohort enrollment among 19,694 participants without a history of cardiovascular disease, diabetes, or cancer. After adjusting for age, adiposity, and other health and behavioral factors, prepregnancy migraine (11%) was associated with higher risks of preterm delivery (RR = 1.17; 95% CI = 1.05-1.30), gestational hypertension (RR = 1.28; 95% CI = 1.11-1.48), and preeclampsia (RR = 1.40; 95% CI = 1.19-1.65) compared with no migraine. Migraine was not associated with low birthweight (RR = 0.99; 95% CI = 0.85-1.16) or GDM (RR = 1.05; 95% CI = 0.91-1.22). Risk of preeclampsia was somewhat higher among participants with migraine with aura (RR vs no migraine = 1.51; 95% CI = 1.22-1.88) than migraine without aura (RR vs no migraine = 1.30; 95% CI = 1.04-1.61; p-heterogeneity = 0.32), whereas other outcomes were similar by migraine phenotype. Participants with migraine who reported regular prepregnancy aspirin use had lower risks of preterm delivery (<2×/week RR = 1.24; 95% CI = 1.11-1.38; ≥2×/week RR = 0.55; 95% CI = 0.35-0.86; p-interaction < 0.01) and preeclampsia (<2×/week RR = 1.48; 95% CI = 1.25-1.75; ≥2×/week RR = 1.10; 95% CI = 0.62-1.96; p-interaction = 0.39); however, power for these stratified analyses was limited. DISCUSSION: Migraine history, and to a lesser extent migraine phenotype, appear to be important considerations in obstetric risk assessment and management. Future research should determine whether aspirin prophylaxis may be beneficial for preventing adverse pregnancy outcomes among pregnant individuals with a history of migraine.

Cardiovascular Risk Factors Mediate the Long-Term Maternal Risk Associated With Hypertensive Disorders of Pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, are associated with an increased risk of CVD. OBJECTIVES: The purpose of this study was to evaluate associations between HDP and long-term CVD and identify the proportion of the association mediated by established CVD risk factors. METHODS: Parous participants without CVD in the Nurses' Health Study II (n = 60,379) were followed for incident CVD from first birth through 2017. Cox proportional hazards models estimated HRs and 95% CIs for the relationship between HDP and CVD, adjusting for potential confounders, including prepregnancy body mass index, smoking, and parental history of CVD. To evaluate the proportion of the association jointly accounted for by chronic hypertension, hypercholesterolemia, type 2 diabetes, and changes in body mass index, we used the difference method. RESULTS: Women with HDP in first pregnancy had a 63% higher rate of CVD (95% CI: 1.37-1.94) compared with women with normotensive pregnancies. This association was mediated by established CVD risk factors (proportion mediated = 64%). The increased rate of CVD was higher for preeclampsia (HR: 1.72; 95% CI: 1.42-2.10) than gestational hypertension (HR: 1.41; 95% CI: 1.03-1.93). Established CVD risk factors accounted for 57% of the increased rate of CVD for preeclampsia but 84% for gestational hypertension (both P < 0.0001). CONCLUSIONS: Established CVD risk factors arising after pregnancy explained most (84%) of the increased risk of CVD conferred by gestational hypertension and 57% of the risk among women with preeclampsia. Screening for chronic hypertension, hypercholesterolemia, type 2 diabetes, and overweight/obesity after pregnancy may be especially helpful in CVD prevention among women with a history of HDP.

Physical activity before pregnancy and the risk of hypertensive disorders of pregnancy.

BACKGROUND: It is unclear whether prepregnancy physical activity influences the risk of hypertensive disorders of pregnancy and whether any impact is similar for preeclampsia and gestational hypertension. OBJECTIVE: To evaluate the relation of prepregnancy physical activity with hypertensive disorders of pregnancy and its alignment with the current recommendations for physical activity for the general population. STUDY DESIGN: We studied 28,147 singleton pregnancies from 18,283 women without chronic hypertension, cardiovascular disease, or cancer, participating in the Nurses' Health Study-II between 1989 and 2010. The women self-reported their physical activity before pregnancy and pregnancy complications, including preeclampsia and gestational hypertension. Logistic regression models using generalized estimating equations to account for within-woman correlations across pregnancies were used to estimate the relative risk (95% confidence interval) of preeclampsia and gestational hypertension across quartiles of prepregnancy physical activity, adjusting for age at pregnancy, parity, smoking, multivitamin use, infertility history, marital status, race, year of pregnancy, and history of preeclampsia. RESULTS: We identified 842 (3.0%) pregnancies with preeclampsia and 905 (3.2%) pregnancies with gestational hypertension. Physical activity before pregnancy was related to a lower risk of hypertensive disorders of pregnancy (relative risk, 0.75 [95% confidence interval, 0.65-0.87] for women in the highest quartile compared with the lowest quartile). This relation was driven by a 39% lower risk of gestational hypertension (relative risk, 0.61; 95% confidence interval, 0.50-0.76) comparing women in the highest quartile of physical activity (≥30.6 metabolic equivalents of task-hours/week) vs women in the lowest quartile (<6.0 metabolic equivalents of task-hours/week). Women whose moderate physical activity levels exceeded those recommended in the Physical Activity Guidelines for Americans (>5 hours/week) had a 50% lower (relative risk, 0.50; 95% confidence interval, 0.36-0.69) risk of gestational hypertension than women who did not meet this recommendation (<2.5 hours/week). For vigorous physical activity, the risk of gestational hypertension was lower among the women who met (1.25-2.5 hours/week; relative risk, 0.77; 95% confidence interval, 0.64-0.93) or exceeded (>2.5 hours/week; relative risk, 0.76; 95% confidence interval, 0.62-0.92) the recommendations than women whose activity levels were below those recommended. Physical activity was not related to the risk of preeclampsia (relative risk, 0.93; 95% confidence interval, 0.76-1.14). CONCLUSION: Physical activity before pregnancy may lower the risk of developing gestational hypertension but not preeclampsia.

Hypertensive Disorders of Pregnancy and Subsequent Risk of Premature Mortality.

BACKGROUND: Hypertensive disorders of pregnancy (HDPs) are leading causes of maternal and perinatal morbidity and mortality. However, it is uncertain whether HDPs are associated with long-term risk of premature mortality (before age 70 years). OBJECTIVES: The objective of this study was to evaluate whether HDPs were associated with premature mortality. METHODS: Between 1989 and 2017, the authors followed 88,395 parous female nurses participating in the Nurses' Health Study II. The study focused on gestational hypertension and pre-eclampsia within the term HDPs. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between HDPs and premature mortality were estimated by using Cox proportional hazards models, with adjustment for relevant confounders. RESULTS: The authors documented that 2,387 women died before age 70 years, including 1,141 cancer deaths and 212 CVD deaths. The occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an HR of 1.31 (95% CI: 1.18 to 1.46) for premature death during follow-up. When specific causes of death were examined, these relations were strongest for CVD-related mortality (HR: 2.26; 95% CI: 1.67 to 3.07). The association between HDPs and all-cause premature death persisted, regardless of the subsequent development of chronic hypertension (HR: 1.20 [95% CI: 1.02 to 1.40] for HDPs only and HR: 2.02 [95% CI: 1.75 to 2.33] for both HDPs and subsequent chronic hypertension). CONCLUSIONS: An occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an increased risk of premature mortality, particularly CVD mortality, even in the absence of chronic hypertension.

Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study.

OBJECTIVE: To evaluate whether irregular or long menstrual cycles throughout the life course are associated with all cause and cause specific premature mortality (age <70 years). DESIGN: Prospective cohort study. SETTING: Nurses' Health Study II (1993-2017). PARTICIPANTS: 79 505 premenopausal women without a history of cardiovascular disease, cancer, or diabetes and who reported the usual length and regularity of their menstrual cycles at ages 14-17 years, 18-22 years, and 29-46 years. MAIN OUTCOME MEASURES: Hazard ratios and 95% confidence intervals for all cause and cause specific premature mortality (death before age 70 years) were estimated from multivariable Cox proportional hazards models. RESULTS: During 24 years of follow-up, 1975 premature deaths were documented, including 894 from cancer and 172 from cardiovascular disease. Women who reported always having irregular menstrual cycles experienced higher mortality rates during follow-up than women who reported very regular cycles in the same age ranges. The crude mortality rate per 1000 person years of follow-up for women reporting very regular cycles and women reporting always irregular cycles were 1.05 and 1.23 for cycle characteristics at ages 14-17 years, 1.00 and 1.37 for cycle characteristics at ages 18-22 years, and 1.00 and 1.68 for cycle characteristics at ages 29-46 years. The corresponding multivariable adjusted hazard ratios for premature death during follow-up were 1.18 (95% confidence interval 1.02 to 1.37), 1.37 (1.09 to 1.73), and 1.39 (1.14 to 1.70), respectively. Similarly, women who reported that their usual cycle length was 40 days or more at ages 18-22 years and 29-46 years were more likely to die prematurely than women who reported a usual cycle length of 26-31 days in the same age ranges (1.34, 1.06 to 1.69; and 1.40, 1.17 to 1.68, respectively). These relations were strongest for deaths related to cardiovascular disease. The higher mortality associated with long and irregular menstrual cycles was slightly stronger among current smokers. CONCLUSIONS: Irregular and long menstrual cycles in adolescence and adulthood are associated with a greater risk of premature mortality (age <70 years). This relation is slightly stronger among women who smoke.

Does pregnancy complication history improve cardiovascular disease risk prediction? Findings from the HUNT study in Norway.

AIM: To evaluate whether history of pregnancy complications [pre-eclampsia, gestational hypertension, preterm delivery, or small for gestational age (SGA)] improves risk prediction for cardiovascular disease (CVD). METHODS AND RESULTS: This population-based, prospective cohort study linked data from the HUNT Study, Medical Birth Registry of Norway, validated hospital records, and Norwegian Cause of Death Registry. Using an established CVD risk prediction model (NORRISK 2), we predicted 10-year risk of CVD (non-fatal myocardial infarction, fatal coronary heart disease, and non-fatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and HDL-cholesterol, smoking, anti-hypertensives, and family history of myocardial infarction). We evaluated whether adding pregnancy complication history improved model fit, calibration, discrimination, and reclassification. Among 18 231 women who were parous, ≥40 years of age, and CVD-free at start of follow-up, 39% had any pregnancy complication history and 5% experienced a CVD event during a median follow-up of 8.2 years. While pre-eclampsia and SGA were associated with CVD in unadjusted models (HR 1.96, 95% CI 1.44-2.65 for pre-eclampsia and HR 1.46, 95% CI 1.18-1.81 for SGA), only pre-eclampsia remained associated with CVD after adjusting for established risk factors (HR 1.60, 95% CI 1.16-2.17). Adding pregnancy complication history to the established prediction model led to small improvements in discrimination (C-index difference 0.004, 95% CI 0.002-0.006) and reclassification (net reclassification improvement 0.02, 95% CI 0.002-0.05). CONCLUSION: Pre-eclampsia independently predicted CVD after controlling for established risk factors; however, adding pre-eclampsia, gestational hypertension, preterm delivery, and SGA made only small improvements to CVD prediction among this representative sample of parous Norwegian women.

Preterm Delivery and Maternal Cardiovascular Disease Risk Factors: The Nurses' Health Study II.

Background: Preterm delivery has been linked to future maternal cardiovascular disease (CVD); however, research investigating clinical CVD risk factors is limited. We evaluated whether women who have delivered an infant preterm are at higher risk of developing CVD risk factors after adjustment for prepregnancy confounders. Materials and Methods: We examined the association between preterm delivery and incident chronic hypertension, type 2 diabetes mellitus (T2DM), and hypercholesterolemia among 57,904 parous women in the Nurses' Health Study II. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between preterm delivery in first pregnancy and each CVD risk factor; adjusted cumulative incidence curves were computed using the Breslow estimator. Results: Preterm delivery (<37 weeks) was associated with HRs of 1.11 (95% CI: 1.06-1.17) for chronic hypertension, 1.17 (95% CI: 1.03-1.33) for T2DM, and 1.07 (95% CI: 1.03-1.11) for hypercholesterolemia, adjusting for age, race/ethnicity, parental education, and prepregnancy confounders (e.g., body mass index, smoking, and family history). HRs were higher in women who delivered very preterm (<32 weeks) and in the first 10 years after first birth. The cumulative incidence of each risk factor was highest in women who delivered very preterm. Conclusions: Women with a history of preterm delivery are at higher risk of developing chronic hypertension, T2DM, and hypercholesterolemia in the years after pregnancy. This increased risk was particularly pronounced in the first 10 years after a preterm delivery, indicating that it may be an important time period to implement lifestyle interventions.

Cardiovascular biomarkers in the years following pregnancies complicated by hypertensive disorders or delivered preterm.

BACKGROUND: Women with a history of hypertensive disorders of pregnancy and preterm delivery have an increased risk of cardiovascular disease (CVD). Chronic inflammation, endothelial dysfunction, and dyslipidemia may link pregnancy outcomes with CVD. OBJECTIVE: We evaluated whether women with a history of HDP or normotensive preterm delivery had adverse CVD biomarker profiles after pregnancy. STUDY DESIGN: We identified parous women from the Nurses' Health Study II with C-reactive protein (CRP; n = 2614), interleukin-6 (IL-6; n = 2490), glycated hemoglobin (n = 885), intracellular adhesion molecule-1 (n = 1231), high density lipoprotein cholesterol (n = 931), low density lipoprotein cholesterol (n = 931), triglycerides (n = 1428), or total cholesterol (n = 2940) assessed in stored blood samples. Multivariable-adjusted robust linear regression models evaluated percent differences and 95% confidence intervals (CIs) in each biomarker associated with a history of HDP or preterm delivery. RESULTS: Ten percent of women had a history of HDP, while 11% with normotensive pregnancies had at least one preterm delivery. Median time from first pregnancy to blood draw was 17 years (interquartile range: 12, 22). Plasma levels of CRP and IL-6 were 34.4% (95% CI: 17.2, 54.1), and 11.6% higher (95% CI: 2.1, 21.9) respectively, among women with a history of HDP compared to those with only normotensive pregnancies. Altered CVD biomarker levels were otherwise not present in women with a history of HDP or preterm delivery. CONCLUSION: CRP and IL-6, but not other CVD biomarkers, were elevated in women with a history of HDP in the years following pregnancy, suggesting inflammation may be a pathway linking HDP with future CVD risk.

Hypertensive Disorders of Pregnancy and 10-Year Cardiovascular Risk Prediction.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) affect 10% to 15% of women and are associated with a 2-fold increased risk of cardiovascular disease (CVD). OBJECTIVES: This study sought to determine whether inclusion of HDP in an established CVD risk score improves prediction of CVD events in women. METHODS: The analysis comprised 106,230 ≤10-year observations contributed by 67,406 women, age ≥40 years, free of prior CVD, with data available on model covariates in the Nurses' Health Study II. Participants were followed up for confirmed myocardial infarction, fatal coronary heart disease, or stroke from 1989 to 2013. We fit an established CVD risk prediction model (Model A: age, total cholesterol and high-density lipoprotein cholesterol, systolic blood pressure, antihypertensive medication use, current smoking, diabetes mellitus) and compared it to the same model plus HDP and parity (Model B); Cox proportional hazards models were used to obtain predicted probabilities for 10-year CVD risk. RESULTS: HDP and parity were associated with 10-year CVD risk independent of established CVD risk factors, overall and at ages 40 to 49 years. However, inclusion of HDP and parity in the risk prediction model did not improve discrimination (Model A: C-index = 0.691; Model B: C-index = 0.693; p value for difference = 0.31) or risk reclassification (net reclassification improvement = 0.4%; 95% confidence interval: -0.2 to 1.0%; p = 0.26). CONCLUSIONS: In this first test of the clinical utility of HDP and parity in CVD risk prediction, additional inclusion of HDP and parity in an established risk score did not improve discrimination or reclassification in this low-risk population; this might be because of the known associations between HDP and established CVD risk factors in the reference model.

Association of History of Gestational Diabetes With Long-term Cardiovascular Disease Risk in a Large Prospective Cohort of US Women.

Importance: Previous studies identify gestational diabetes (GD) as a risk factor for intermediate markers of cardiovascular disease (CVD) risk; however, few are prospective, evaluate hard CVD end points, or account for shared risk factors including body weight and lifestyle. Objective: To prospectively evaluate history of GD in relation to incident CVD risk. Design, Setting, and Participants: The Nurses' Health Study II (NHS II) is an observational cohort study of US female nurses established in 1989, with ongoing follow-up. Biennial questionnaires updated behavioral characteristics, health outcomes, and lifestyle factors. Multivariable Cox models estimated the hazard ratio (HR) and 95% CI for CVD risk. We included 89 479 women who reported at least 1 pregnancy and were free of CVD and cancer at baseline. Follow-up through May 31, 2015, was complete for more than 90% of eligible participants. Exposures: History of GD was self-reported at baseline (1989) via questionnaire and updated every 2 years. Main Outcomes and Measures: We observed 1161 incident self-reported nonfatal or fatal myocardial infarction or stroke, confirmed via medical records. Results: Participants had a mean (SD) age of 34.9 (4.7) years. Adjusting for age, prepregnancy body mass index, and other covariates, GD vs no GD was associated with subsequent CVD (HR, 1.43; 95% CI, 1.12-1.81). Additional adjustment for weight gain since pregnancy and updated lifestyle factors attenuated the association (HR, 1.29; 95% CI, 1.01-1.65). Classifying GD by progression to T2D in relation to CVD risk indicated a positive association for GD with progression to T2D vs no GD or T2D (HR, 4.02; 95% CI, 1.94-8.31), and an attenuated relationship for GD only (HR, 1.30; 95% CI, 0.99-1.71). Conclusions and Relevance: Gestational diabetes was positively associated with CVD later in life, although the absolute rate of CVD in this younger cohort of predominantly white women was low. This relationship is possibly mediated in part by subsequent weight gain and lack of healthy lifestyle.

Lifestyle in progression from hypertensive disorders of pregnancy to chronic hypertension in Nurses' Health Study II: observational cohort study.

Objectives To study the association between lifestyle risk factors and chronic hypertension by history of hypertensive disorders of pregnancy (HDP: gestational hypertension and pre-eclampsia) and investigate the extent to which these risk factors modify the association between HDP and chronic hypertension.Design Prospective cohort study.Setting Nurses' Health Study II (1991-2013).Participants 54 588 parous women aged 32 to 59 years with data on reproductive history and without previous chronic hypertension, stroke, or myocardial infarction.Main outcome measure Chronic hypertension diagnosed by a physician and indicated through nurse participant self report. Multivariable Cox proportional hazards models were used to investigate the development of chronic hypertension contingent on history of HDP and four lifestyle risk factors: post-pregnancy body mass index, physical activity, adherence to the Dietary Approaches to Stop Hypertension (DASH) diet, and dietary sodium/potassium intake. Potential effect modification (interaction) between each lifestyle factor and previous HDP was evaluated with the relative excess risk due to interaction.Results 10% (n=5520) of women had a history of HDP at baseline. 13 971 cases of chronic hypertension occurred during 689 988 person years of follow-up. Being overweight or obese was the only lifestyle factor consistently associated with higher risk of chronic hypertension. Higher body mass index, in particular, also increased the risk of chronic hypertension associated with history of HDP (relative excess risk due to interaction P<0.01 for all age strata). For example, in women aged 40-49 years with previous HDP and obesity class I (body mass index 30.0-34.9), 25% (95% confidence interval 12% to 37%) of the risk of chronic hypertension was attributable to a potential effect of obesity that was specific to women with previous HDP. There was no clear evidence of effect modification by physical activity, DASH diet, or sodium/potassium intake on the association between HDP and chronic hypertension.Conclusion This study suggests that the risk of chronic hypertension after HDP might be markedly reduced by adherence to a beneficial lifestyle. Compared with women without a history of HDP, keeping a healthy weight seems to be especially important with such a history.