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Uric Acid: A Missing Link Between Hypertensive Pregnancy Disorders and Future Cardiovascular Disease?

ABSTRACT: To determine whether women who had a hypertensive pregnancy disorder (HPD) have elevated uric acid concentrations decades after pregnancy as compared with women who had normotensive pregnancies.The Genetic Epidemiology Network of Arteriopathy study measured uric acid concentrations in Hispanic (30%), non-Hispanic white (28%), and non-Hispanic black (42%) women (mean age, 60 ± 10 years). This cross-sectional study was conducted between July 1, 2000, and December 31, 2004. Hispanic participants were recruited from families with high rates of diabetes, whereas non-Hispanic participants were recruited from families with high rates of hypertension. This analysis compared uric acid concentrations in women with a history of normotensive (n = 1846) or hypertensive (n = 408) pregnancies by logistic regression.Women who had an HPD had higher uric acid concentrations (median, 5.7 mg/dL vs 5.3 mg/dL; P < .001) and were more likely to have uric acid concentrations above 5.5 mg/dL (54.4% vs 42.4%; P = .001) than were women who had normotensive pregnancies. These differences persisted after adjusting for traditional cardiovascular risk factors, comorbidities, and other factors that affect uric acid concentrations. A family-based subgroup analysis comparing uric acid concentrations in women who had an HPD (n = 308) and their parous sisters who had normotensive pregnancies (n = 250) gave similar results (median uric acid concentrations, 5.7 mg/dL vs 5.2 mg/dL, P = 0.02; proportion of women with uric acid concentrations > 5.5 mg/dL, 54.0% vs 40.3%, P < .001).Decades after pregnancy, women who had an HPD have higher uric acid concentrations. This effect does not appear to be explained by a familial predisposition to elevated uric acid concentrations.

SUBMITTER: Weissgerber TL

PROVIDER: S-EPMC4567408 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Uric Acid: A Missing Link Between Hypertensive Pregnancy Disorders and Future Cardiovascular Disease?

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

Mayo Clinic proceedings 20150807 9

<h4>Objective</h4>To determine whether women who had a hypertensive pregnancy disorder (HPD) have elevated uric acid concentrations decades after pregnancy as compared with women who had normotensive pregnancies.<h4>Patients and methods</h4>The Genetic Epidemiology Network of Arteriopathy study measured uric acid concentrations in Hispanic (30%), non-Hispanic white (28%), and non-Hispanic black (42%) women (mean age, 60 ± 10 years). This cross-sectional study was conducted between July 1, 2000, ...[more]

PMID: 26260220

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Project description:ImportanceHypertensive disorders of pregnancy (HDP) have been associated with poorer neurodevelopmental outcomes in offspring, but the role of familial confounding in these associations is unclear.ObjectiveTo investigate associations of maternal HDP with risks in offspring of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), as well as variation in overall cognitive performance in offspring.Design, setting, and participantsThis Swedish register-based study used data from a birth cohort divided into 1 085 024 individuals born between 1987 and 1996 and followed up until December 31, 2014, and 285 901 men born between 1982 and 1992 who attended assessments for military conscription, including a cognitive function test. Statistical analysis was performed from April 1, 2019, to June 1, 2020.ExposuresDiagnoses of HDP, which were provided by the Medical Birth Register.Main outcomes and measuresDiagnoses of ASDs, ADHD, and ID were extracted from the National Patient Register. Cognitive function was assessed using written tests and summarized as a single 9-point score. Whole-cohort and within-sibship analyses were performed; the latter accounted for unmeasured familial confounding factors shared by siblings.ResultsThe study included 1 085 024 individuals (556 912 male participants [51.3%]) born between 1987 and 1996 and 285 901 men born between 1982 and 1992 who attended assessments for military conscription. The prevalence of maternal HDP was 4.0% in the 1987-1996 birth cohort (n = 42 980) and 5.1% in the military conscription cohort (n = 14 515). A total of 15 858 participants received a diagnosis of ASD, 36 852 received a diagnosis of ADHD, and 8454 received a diagnosis of ID. The mean (SD) cognitive score among the men in the conscription cohort was 5.1 (1.9). In whole-cohort analyses with multivariable adjustment, HDP were associated with offspring ASDs (hazard ratio [HR], 1.22; 95% CI, 1.13-1.31), ADHD (HR, 1.10; 95% CI, 1.05-1.16), and ID (HR, 1.39; 95% CI, 1.27-1.53). Analyses comparing siblings discordant for HDP were less statistically powered but indicated estimates of similar magnitude for ASDs (HR, 1.19; 95% CI, 1.00-1.42) and possibly ADHD (HR, 1.09; 95% CI, 0.95-1.24), but not for ID (HR, 1.04; 95% CI, 0.83-1.29). Hypertensive disorders of pregnancy were associated with somewhat lower cognitive scores in whole-cohort analysis (mean difference comparing offspring exposed with those unexposed, -0.10; 95% CI, -0.13 to -0.07), but in within-sibship analysis, the association was null (mean difference, 0.00; 95% CI, -0.09 to 0.08).Conclusions and relevanceThe study results suggest that HDP are associated with small increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely confounded by shared familial (environmental or genetic) factors.

Project description:INTRODUCTION:A high level of uric acid (UA) is a strong, independent risk factor for type 2 diabetes mellitus. The relationship between UA levels and the development of type 2 diabetes in women with previous gestational diabetes mellitus (pGDM) remains unclear. The aim of study was to evaluate the UA levels in pGDM women in relation to their current nutritional status and carbohydrate metabolism. MATERIAL AND METHODS:199 women with pGDM diagnoses based on oral glucose tolerance tests (OGTTs) 5-12 years previously and a control group of 50 women without pGDM. The assessment included anthropometric parameters, body composition (Tanita SC-330S), current OGTT, insulin resistance index (HOMA-IR), ?-cell function (HOMA-%B), HbA1c, lipids, and uric acid. RESULTS:No differences between groups were found in terms of age, time from the index pregnancy, anthropometric parameters, lipids or creatinine levels. The incidences of overweight and obesity were similar. Carbohydrate abnormalities were more frequent in the pGDM group than the control group (43.2% vs 12.0% p<0.001). The women with pGDM had significantly higher fasting glucose, HbA1c, glucose and insulin levels in the OGTTs, but similar HOMA-IR values. Their UA levels were significantly higher (258±58 vs 230±50 ?mol/L, p<0.005) and correlated with BMI and the severity of carbohydrate disorders. The normal weight and normoglycemic pGDM women also demonstrated higher UA levels than a similar control subgroup (232±48 vs 208±48 ?mol/L, p<0.05). Multivariate analysis revealed significant correlations of UA level with BMI (? = 0.38, 95% CI 0.25-0.51, p<0.0001), creatinine level (? = 0.23, 95% CI 0.11-0.35, p<0.0005), triglycerides (? = 0.20, 95% CI 0.07-0.33, p<0.005) and family history of diabetes (? = 0.13, 95% CI 0.01-0.25, p<0.05). In logistic regression analysis, the association between higher UA level (defined as value ?297 ?mol/L) and presence of any carbohydrate metabolism disorder (IFG, IGT or diabetes) was statistically significant (odds ratio 3.62 [95% CI 1.8-7.3], p<0.001). CONCLUSIONS:Higher UA levels may be associated with the development of type 2 diabetes in pGDM women, also in these with normal body weights.

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Uric Acid: A Missing Link Between Hypertensive Pregnancy Disorders and Future Cardiovascular Disease?

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Uric Acid: A Missing Link Between Hypertensive Pregnancy Disorders and Future Cardiovascular Disease?

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