No accelerated arterial aging in relatively young women after preeclampsia as compared to normotensive pregnancy.

Introduction: Preeclampsia, an endothelial disorder of pregnancy, predisposes to remote cardiovascular diseases (CVD). Whether there is an accelerated effect of aging on endothelial decline in former preeclamptic women is unknown. We investigated if the arterial aging regarding endothelial-dependent and -independent vascular function is more pronounced in women with a history of preeclampsia as compared to women with a history of solely normotensive gestation(s). Methods: Data was used from the Queen of Hearts study (ClinicalTrials.gov Identifier NCT02347540); a large cross-sectional study on early detection of cardiovascular disease among young women (≥18 years) with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancies. Brachial artery flow-mediated dilation (FMD; absolute, relative and allometric) and sublingually administered nitroglycerine-mediated dilation (NGMD; absolute and relative) were measured using ultrasound. Cross-sectional associations of age with FMD and NGMD were investigated by linear regression. Models were adjusted for body mass index, smoking, antihypertensive drug use, mean arterial pressure, fasting glucose, menopausal state, family history of CVD and stress stimulus during measurement. Effect modification by preeclampsia was investigated by including an interaction term between preeclampsia and age in regression models. Results: Of the 1,217 included women (age range 22-62 years), 66.0% had a history of preeclampsia and 34.0% of normotensive pregnancy. Advancing age was associated with a decrease in relative FMD and NGMD (unadjusted regression coefficient: FMD: -0.48%/10 years (95% CI:-0.65 to -0.30%/10 years), NGMD: -1.13%/10 years (-1.49 to -0.77%/10 years)) and increase in brachial artery diameter [regression coefficient = 0.16 mm/10 years (95% CI 0.13 to 0.19 mm/10 years)]. Similar results were found when evaluating FMD and NGMD as absolute increase or allometrically, and after confounder adjustments. These age-related change were comparable in former preeclamptic women and controls (p-values interaction ≥0.372). Preeclampsia itself was independently associated with consistently smaller brachial artery diameter, but not with FMD and NGMD. Conclusion: In young- to middle-aged women, vascular aging in terms of FMD and NGMD was not accelerated in women after preeclampsia compared to normotensive pregnancies, even though former preeclamptic women consistently have smaller brachial arteries.

The risk matrix approach: a helpful tool weighing probability and impact when deciding on preventive and diagnostic interventions.

BACKGROUND: Clinical guidelines are developed to lower risks, mostly viewed upon as probability. However, in daily practice, risk is perceived as the combination of probability and the impact of desired and adverse events. This combination of probability and impact can be visualized in a risk matrix. We evaluated the effect of interventions and diagnostic thresholds on modeled risk, by using the risk matrix approach (RMA) in a clinical guideline development process, and investigated which additional factors affected choices. METHODS: To improve care outcomes, we developed new guidelines in which care professionals had to decide upon novel interventions and diagnostic thresholds. A risk matrix showed the probability and impact of an intervention, together with the corresponding risk category. First, professionals' opinion on required performance characteristics on risk were evaluated by a qualitative online survey. Second, qualitative assessment of possible additional factors affecting final decisions, that followed from group discussion and guideline development were evaluated. RESULTS: Upfront, professionals opinioned that non-invasive interventions should decrease the general population risk, whereas invasive interventions should decrease the risk in high-risk groups. Nonetheless, when making guidelines, interventions were introduced without reaching the predefined threshold of desired risk reduction. Professionals weighed other aspects besides risk reduction, as financial aspects and practical consequences for daily practice in this guideline-making process. CONCLUSION: Professionals are willing to change policies at much lower level of anticipated effectiveness than defined upfront. Although objectively presented data structured group discussions, decisions in guideline development are affected by several other factors than risk reduction alone.

Preventing Recurrent Preeclampsia by Tailored Treatment of Nonphysiologic Hemodynamic Adjustments to Pregnancy.

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Endothelial and kidney function in women with a history of preeclampsia and healthy parous controls: A case control study.

INTRODUCTION: Preeclampsia (PE) is a pregnancy related endothelial disease characterized by hypertension and albuminuria. Postpartum endothelial dysfunction often persists in these women. We postulate that in women with a history of PE reduced endothelial dependent vasodilation coincides with attenuated kidney function, as both reflect endothelial dysfunction. METHODS: We assessed endothelial and kidney function in women with a history of PE (n=79) and uncomplicated pregnancies (n=49) at least 4years postpartum. Women with hypertension, diabetes or kidney disease prior to pregnancy were excluded. Brachial artery flow mediated dilatation (FMD) was measured and analysed by a custom designed edge-detection and wall-tracking software. We measured albumin and creatinine levels in a 24-h urine sample and calculated glomerular filtration rate (GFR) by CKD-EPI. RESULTS: Women with a history of PE had lower FMD but comparable GFR and albumin creatinine ratio (ACR) compared with controls. Independent of obstetric history, in both controls and women with a history of PE respectively, GFR (r=0.19, p=0.17 and r=0.12, p=0.29) and albumin creatinine ratio (r=0.07, p=0.62 and r=0.06 p=0.57) did not correlate with FMD. CONCLUSION: At least 4years after pregnancy, women with a history of PE demonstrated decreased flow mediated dilatation when compared to healthy parous controls. In this study, decreased flow mediated dilation however did not coincide with decreased kidney function.

Homeostatic model assessment of beta cell function predicting abnormal oral glucose tolerance testing in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) complicates 1-14% of pregnancies and relates to increased risk of adverse obstetric outcomes. Currently GDM is diagnosed using an oral glucose tolerance test (OGTT), which is burdensome and time intensive. OBJECTIVE: To compare current literature on whether the homeostatic model assessment beta cell function (HOMA-ß) is an accurate predictor of an abnormal OGTT in pregnant women. METHODS: Pubmed, Cochrane and Embase were searched. Included studies evaluated pregnant women at risk for GDM using the homeostatic model assessment of beta cell function (HOMA-ß) for the assessment of beta cell function and the OGTT. Studies with animals, non-pregnant women, women with type 2 diabetes and post-partum diabetes were excluded. The QUADAS-2 criteria were used to assess the methodological quality of studies. RESULTS: A total of 12 studies were included, reporting on 7292 women. Seven studies showed a difference in beta cell function between women with impaired glucose tolerance compared to healthy pregnant women. HOMA-ß is significantly lower in impaired glucose tolerance (p < 0.001). CONCLUSIONS: Although HOMA-ß is lower in women with abnormal OGTT in pregnancy, given the high degree of heterogeneity of studies, we do not propagate HOMA-ß as a sole diagnostic tool replacing OGTT to diagnose GDM.