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Hypertension in Pregnancy and Future Cardiovascular Event Risk in Siblings.

ABSTRACT: Hypertension in pregnancy is a risk factor for future hypertension and cardiovascular disease. This may reflect an underlying familial predisposition or persistent damage caused by the hypertensive pregnancy. We sought to isolate the effect of hypertension in pregnancy by comparing the risk of hypertension and cardiovascular disease in women who had hypertension in pregnancy and their sisters who did not using the dataset from the Genetic Epidemiology Network of Arteriopathy study, which examined the genetics of hypertension in white, black, and Hispanic siblings. This analysis included all sibships with at least one parous woman and at least one other sibling. After gathering demographic and pregnancy data, BP and serum analytes were measured. Disease-free survival was examined using Kaplan-Meier curves and Cox proportional hazards regression. Compared with their sisters who did not have hypertension in pregnancy, women who had hypertension in pregnancy were more likely to develop new onset hypertension later in life, after adjusting for body mass index and diabetes (hazard ratio 1.75, 95% confidence interval 1.27-2.42). A sibling history of hypertension in pregnancy was also associated with an increased risk of hypertension in brothers and unaffected sisters, whereas an increased risk of cardiovascular events was observed in brothers only. These results suggest familial factors contribute to the increased risk of future hypertension in women who had hypertension in pregnancy. Further studies are needed to clarify the potential role of nonfamilial factors. Furthermore, a sibling history of hypertension in pregnancy may be a novel familial risk factor for future hypertension.

SUBMITTER: Weissgerber TL

PROVIDER: S-EPMC4769201 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Hypertension in Pregnancy and Future Cardiovascular Event Risk in Siblings.

Weissgerber Tracey L TL Turner Stephen T ST Mosley Thomas H TH Kardia Sharon L R SL Hanis Craig L CL Milic Natasa M NM Garovic Vesna D VD

Journal of the American Society of Nephrology : JASN 20150827 3

Hypertension in pregnancy is a risk factor for future hypertension and cardiovascular disease. This may reflect an underlying familial predisposition or persistent damage caused by the hypertensive pregnancy. We sought to isolate the effect of hypertension in pregnancy by comparing the risk of hypertension and cardiovascular disease in women who had hypertension in pregnancy and their sisters who did not using the dataset from the Genetic Epidemiology Network of Arteriopathy study, which examine ...[more]

PMID: 26315531

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Project description:BackgroundHistory of a hypertensive disorder of pregnancy (HDP) among women may be useful to refine atherosclerotic cardiovascular disease risk assessments. However, future risk of diverse cardiovascular conditions in asymptomatic middle-aged women with prior HDP remains unknown.ObjectivesThe purpose of this study was to examine the long-term incidence of diverse cardiovascular conditions among middle-aged women with and without prior HDP.MethodsWomen in the prospective, observational UK Biobank age 40 to 69 years who reported ≥1 live birth were included. Noninvasive arterial stiffness measurement was performed in a subset of women. Cox models were fitted to associate HDP with incident cardiovascular diseases. Causal mediation analyses estimated the contribution of conventional risk factors to observed associations.ResultsOf 220,024 women included, 2,808 (1.3%) had prior HDP. The mean age at baseline was 57.4 ± 7.8 years, and women were followed for median 7 years (interquartile range: 6.3 to 7.7 years). Women with HDP had elevated arterial stiffness indexes and greater prevalence of chronic hypertension compared with women without HDP. Overall, 7.0 versus 5.3 age-adjusted incident cardiovascular conditions occurred per 1,000 women-years for women with versus without prior HDP, respectively (p = 0.001). In analysis of time-to-first incident cardiovascular diagnosis, prior HDP was associated with a hazard ratio (HR) of 1.3 (95% CI: 1.04 to 1.60; p = 0.02). HDP was associated with greater incidence of CAD (HR: 1.8; 95% CI: 1.3 to 2.6; p < 0.001), heart failure (HR: 1.7; 95% CI: 1.04 to 2.60; p = 0.03), aortic stenosis (HR: 2.9; 95% CI: 1.5 to 5.4; p < 0.001), and mitral regurgitation (HR: 5.0; 95% CI: 1.5 to 17.1; p = 0.01). In causal mediation analyses, chronic hypertension explained 64% of HDP's association with CAD and 49% of HDP's association with heart failure.ConclusionsHypertensive disorders of pregnancy are associated with accelerated cardiovascular aging and more diverse cardiovascular conditions than previously appreciated, including valvular heart disease. Cardiovascular risk after HDP is largely but incompletely mediated by development of chronic hypertension.

Project description:Background Inconsistent findings have been found among studies evaluating the risk of cardiovascular disease for women who have had pregnancies complicated by gestational hypertension (the new onset of high blood pressure without proteinuria during pregnancy). We provide a comprehensive review of studies to quantify the association between gestational hypertension and cardiovascular events in women. Methods and Results We conducted a systematic search of PubMed, Embase, and Web of Science in March 2019 for studies examining the association between gestational hypertension and any cardiovascular event. Two reviewers independently assessed the abstracts and full-text articles. Study characteristics and the relative risk (RR) of cardiovascular events associated with gestational hypertension were extracted from the eligible studies. Where appropriate, the estimates were pooled with inverse variance weighted random-effects meta-analysis. A total of 21 studies involving 3 60 1192 women (127 913 with gestational hypertension) were identified. Gestational hypertension in the first pregnancy was associated with a greater risk of overall cardiovascular disease (RR, 1.45; 95% CI, 1.17-1.80) and coronary heart disease (RR, 1.46; 95% CI, 1.23-1.73), but not stroke (RR, 1.26; 95% CI, 0.96-1.65) or thromboembolic events (RR, 0.88; 95% CI, 0.73-1.07). Women with 1 or more pregnancies affected by gestational hypertension were at greater risk of cardiovascular disease (RR, 1.81; 95% CI, 1.42-2.31), coronary heart disease (RR, 1.83; 95% CI, 1.33-2.51), and heart failure (RR, 1.77; 95% CI, 1.47-2.13), but not stroke (RR, 1.50; 95% CI, 0.75-2.99). Conclusions Gestational hypertension is associated with a greater risk of overall cardiovascular disease, coronary heart disease, and heart failure. More research is needed to assess the presence of a dose-response relationship between gestational hypertension and subsequent cardiovascular disease. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42018119031.

Project description:ImportanceHypertensive disorders in pregnancy (HDPs) are major causes of maternal and fetal morbidity and are observationally associated with future maternal risk of cardiovascular disease. However, observational results may be subject to residual confounding and bias.ObjectiveTo investigate the association of HDPs with multiple cardiovascular diseases.Design, setting, and participantsA genome-wide genetic association study using mendelian randomization (MR) was performed from February 16 to March 4, 2022. Primary analysis was conducted using inverse-variance-weighted MR. Mediation analyses were performed using a multivariable MR framework. All studies included patients predominantly of European ancestry. Female-specific summary-level data from FinnGen (sixth release).ExposuresUncorrelated (r2<0.001) single-nucleotide variants (SNVs) were selected as instrumental variants from the FinnGen consortium summary statistics for exposures of any HDP, gestational hypertension, and preeclampsia or eclampsia.Main outcomes and measuresGenetic association estimates for outcomes were extracted from genome-wide association studies of 122 733 cases for coronary artery disease, 34 217 cases for ischemic stroke, 47 309 cases for heart failure, and 60 620 cases for atrial fibrillation.ResultsGenetically predicted HDPs were associated with a higher risk of coronary artery disease (odds ratio [OR], 1.24; 95% CI, 1.08-1.43; P = .002); this association was evident for both gestational hypertension (OR, 1.08; 95% CI, 1.00-1.17; P = .04) and preeclampsia/eclampsia (OR, 1.06; 95% CI, 1.01-1.12; P = .03). Genetically predicted HDPs were also associated with a higher risk of ischemic stroke (OR, 1.27; 95% CI, 1.12-1.44; P = 2.87 × 10-4). Mediation analysis revealed a partial attenuation of the effect of HDPs on coronary artery disease after adjustment for systolic blood pressure (total effect OR, 1.24; direct effect OR, 1.10; 95% CI, 1.02-1.08; P = .02) and type 2 diabetes (total effect OR, 1.24; direct effect OR, 1.16; 95% CI, 1.04-1.29; P = .008). No associations were noted between genetically predicted HDPs and heart failure (OR, 0.97; 95% CI, 0.76-1.23; P = .79) or atrial fibrillation (OR, 1.11; 95% CI, 0.65-1.88; P = .71).Conclusions and relevanceThe findings of this study provide genetic evidence supporting an association between HDPs and higher risk of coronary artery disease and stroke, which is only partially mediated by cardiometabolic factors. This supports classification of HDPs as risk factors for cardiovascular disease.

Dataset Information

Hypertension in Pregnancy and Future Cardiovascular Event Risk in Siblings.

Publications

Hypertension in Pregnancy and Future Cardiovascular Event Risk in Siblings.

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