Pregnancy and Long-Term Maternal Cardiovascular Health

Staff, Anne Cathrine; Redman, Christopher W.G.; Williams, D. Innes; Leeson, Paul; Moe, Kjartan; Thilaganathan, B.; Magnus, Per; Steegers, Eric A.P.; Tsigas, Eleni; Ness, Roberta B.; Myatt, Leslie; Poston, Lucilla; Roberts, James M.

doi:10.1161/hypertensionaha.115.06357

Cited by 123 publications

(51 citation statements)

References 106 publications

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“…In 6000 women in the National Health and Nutrition Examination Survey, preterm SGA was a significant predictor of hypertension only in non‐Hispanic blacks 47. It is postulated that the more severe the placental dysfunction, the higher the risk for maternal premature CVD 48. Our SGA results may relate, in part, to having more healthy study participants than the general population; our rates of SGA and very SGA were lower than anticipated (7.1% and 1.4% versus the expected 10% and 2.5%, respectively).…”

Section: Discussionmentioning

confidence: 99%

Pregnancy‐Related Risk Factors Are Associated With a Significant Burden of Treated Hypertension Within 10 Years of Delivery: Findings From a Population‐Based Norwegian Cohort

Egeland

Staff

Eide

et al. 2018

JAHA

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BackgroundThe association between pregnancy complications and women's later cardiovascular disease has, primarily, been evaluated in studies lacking information on important covariates. This report evaluates the prospective associations between pregnancy‐related risk factors (preeclampsia/eclampsia, gestational hypertension, pregestational and gestational diabetes mellitus, preterm delivery, and fetal growth restriction) and pharmacologically treated hypertension within 10 years after pregnancy, while adjusting for a wide range of covariates.Methods and ResultsPrepregnancy normotensive women participating in the MoBa (Norwegian Mother and Child Cohort Study) from January 2004 through July 2009 were linked to the Norwegian Prescription Database to identify women with pharmacologically treated hypertension beyond the postpartum period of 3 months. The burden of hypertension associated with pregnancy‐related risk factors was evaluated using an attributable fraction method. A total of 1480 women developed pharmacologically treated hypertension within the follow‐up among 60 027 women (rate of hypertension, 3.6/1000 person‐years). The proportion of hypertension associated with a history of preeclampsia/eclampsia, gestational hypertension, preterm delivery, and pregestational or gestational diabetes mellitus was 28.6% (95% confidence interval, 25.5%–31.6%) on the basis of multivariable analyses adjusting for numerous covariates. The proportion was similar for women with a healthy prepregnancy body mass index (18.5‐24.9 kg/m2; attributable fraction (AF)% 25.9%; 95% confidence interval, 21.3%‐30.3%), but considerably higher for nulliparous women at baseline within the first 5 years of follow‐up. Small‐for‐gestational age, however, did not increase subsequent hypertension risk in multivariable analyses.ConclusionsA structured postpartum follow‐up of high‐risk women identified through pregnancy‐related risk factors would facilitate personalized preventive strategies to postpone or avoid onset of premature cardiovascular events.

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Section: Discussionmentioning

confidence: 99%

Pregnancy‐Related Risk Factors Are Associated With a Significant Burden of Treated Hypertension Within 10 Years of Delivery: Findings From a Population‐Based Norwegian Cohort

Egeland

Staff

Eide

et al. 2018

JAHA

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“…Among the genes where associating SNPs have been described are genes linked to hypertension and vascular and metabolic disease (2–4), all diseases whose risk is increased in the later life of PE patients (5). Furthermore, genes encoding for proteins involved in the immunological processes have also been found to harbor SNPs that predispose patients to PE (6, 7).…”

Section: Introductionmentioning

confidence: 99%

Analysis of Complement C3 Gene Reveals Susceptibility to Severe Preeclampsia

et al. 2017

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Preeclampsia (PE) is a common vascular disease of pregnancy with genetic predisposition. Dysregulation of the complement system has been implicated, but molecular mechanisms are incompletely understood. In this study, we determined the potential linkage of severe PE to the most central complement gene, C3. Three cohorts of Finnish patients and controls were recruited for a genetic case-control study. Participants were genotyped using Sequenom genotyping and Sanger sequencing. Initially, we studied 259 Finnish patients with severe PE and 426 controls from the Southern Finland PE and the Finnish population-based PE cohorts. We used a custom-made single nucleotide polymorphism (SNP) genotyping assay consisting of 98 SNPs in 18 genes that encode components of the complement system. Following the primary screening, C3 was selected as the candidate gene and consequently Sanger sequenced. Fourteen SNPs from C3 were also genotyped by a Sequenom panel in 960 patients with severe PE and 705 controls, including already sequenced individuals. Three of the 43 SNPs observed within C3 were associated with severe PE: rs2287845 (p = 0.038, OR = 1.158), rs366510 (p = 0.039, OR = 1.158), and rs2287848 (p = 0.041, OR = 1.155). We also discovered 16 SNP haplotypes with extreme linkage disequilibrium in the middle of the gene with a protective (p = 0.044, OR = 0.628) or a predisposing (p = 0.011, OR = 2.110) effect to severe PE depending on the allele combination. Genetic variants associated with PE are located in key domains of C3 and could thereby influence the function of C3. This is, as far as we are aware, the first candidate gene in the complement system with an association to a clinically relevant PE subphenotype, severe PE. The result highlights a potential role for the complement system in the pathogenesis of PE and may help in defining prognostic and therapeutic subgroups of preeclamptic women.

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“…The clinical characteristics are diverse and the course of the disease is unpredictable. Both a PE mother and a child born from a PE pregnancy are at higher risk for later-life cardiovascular diseases and type 2 diabetes 4 .…”

Section: Introductionmentioning

confidence: 99%

Protective Low-Frequency Variants for Preeclampsia in the Fms Related Tyrosine Kinase 1 Gene in the Finnish Population

et al. 2017

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Preeclampsia is a common pregnancy-specific vascular disorder characterized by new-onset hypertension and proteinuria during the second half of pregnancy. The etiology of the disease is unknown but predisposition to preeclampsia is in part heritable. Preeclampsia is associated with an increased risk of cardiovascular disease later in life. We have sequenced 124 candidate genes implicated in preeclampsia to pinpoint genetic variants contributing to predisposition to or protection from preeclampsia. First, targeted exomic sequencing was carried out in 500 preeclamptic women and 190 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort. Then 122 women with a history of preeclampsia and 1,905 parous women with no such history from the National FINRISK Study were included in the analyses. We tested 146 rare and low-frequency variants and found an excess (observed 13 versus expected 7.3) nominally associated with preeclampsia (p< 0.05). The most significantly associated sequence variants were protective variants rs35832528 (E982A; p=2.49E-4, OR=0.387) and rs141440705 (R54S; p=0.003, OR=0.442) in Fms Related Tyrosine Kinase 1 (FLT1). These variants are enriched in the Finnish population with minor allele frequencies 0.026 and 0.017, respectively. They may also be associated with a lower risk of heart failure in 11,257 FINRISK women. This study provides the first evidence of maternal protective genetic variants in preeclampsia.

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Pregnancy and Long-Term Maternal Cardiovascular Health

Cited by 123 publications

References 106 publications

Pregnancy‐Related Risk Factors Are Associated With a Significant Burden of Treated Hypertension Within 10 Years of Delivery: Findings From a Population‐Based Norwegian Cohort

Pregnancy‐Related Risk Factors Are Associated With a Significant Burden of Treated Hypertension Within 10 Years of Delivery: Findings From a Population‐Based Norwegian Cohort

Analysis of Complement C3 Gene Reveals Susceptibility to Severe Preeclampsia

Protective Low-Frequency Variants for Preeclampsia in the Fms Related Tyrosine Kinase 1 Gene in the Finnish Population

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