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.

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.

Maternal hemodynamics influence fetal hemodynamics in normal and hypertensive pregnancy.

OBJECTIVES: This observational case-control study aims to test whether there is a relationship between maternal systemic hemodynamics, maternal renin-angiotensin system and fetal hemodynamics in normal and hypertensive pregnancy. STUDY DESIGN: Four groups of non-pregnant women (n=18), pregnant controls (n=25), women with gestational hypertension (n=21) and preeclampsia (n=10) were included. MAIN OUTCOME MEASURES: Maternal echocardiography parameters, plasma renin and aldosterone were correlated with fetal Doppler parameters in third trimester pregnancy. RESULTS: Higher maternal mean arterial pressure and total peripheral vascular resistance were associated with lower fetal middle cerebral artery pulsatility index (PI) (r=-.51, p<0.01 and r=-.49, p<0.01, respectively); mean arterial pressure correlated negatively with ductus venosus PI (r=-.35, p=0.01); higher maternal plasma aldosterone levels were associated with lower maternal uterine artery resistance (r=-0.33, p=0.03). CONCLUSIONS: It seems that maternal hemodynamics influence fetal hemodynamics with protective adaptation in fetal cerebral and ductus venosus blood flow observed as maternal blood pressure and vascular resistance increase.

Metabolic syndrome as a risk factor for hypertension after preeclampsia.

OBJECTIVE: To identify metabolic and obstetric risk factors associated with hypertension after preeclampsia. METHODS: We analyzed demographic and clinical data from a postpartum screening (blood pressure, microalbuminuria and fasting plasma levels of glucose, insulin, and lipid profile) from 683 primiparous women with a history of preeclampsia. We excluded women with pre-existing hypertension, kidney disease, or diabetes mellitus. In the group of women who were normotensive at postpartum screening, we evaluated the risk of developing chronic hypertension in the years after screening using questionnaires. RESULTS: Hypertension at postpartum screening (n=107, 17% of all cases) was related to obesity (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.2), elevated fasting levels of insulin (OR 1.7, 95% CI 1.0-2.9), low-density lipoprotein (OR 1.6, 95% CI 1.1-2.6), microalbuminuria (OR 2.3, 95%-CI 1.3-4.0), family history of hypertension (OR 1.8, 95% CI 1.1-2.8), and delivery before 34 weeks of gestation (OR 2.5, 95% CI 1.6-4.0). We identified 27 cases of hypertension within 2,095 person-years during a median 6-year follow-up in the group of women normotensive at postpartum screening. The hazard rate for the development of hypertension was 2.9 (95% CI 1.2-7.5) and 8.1 (95% CI 2.8-22.9), respectively, when two and three or more components of the metabolic syndrome were present; 3.7 (95% CI 1.4-10.0) for family history of hypertension; and 4.3 (95% CI 1.6-11.5) for recurrence of a hypertensive disorder in pregnancy. CONCLUSION: Several metabolic and obstetric risk factors related to hypertension postpartum in the short term and predisposed to the subsequent development of chronic hypertension after preeclampsia in initially normotensive women. LEVEL OF EVIDENCE: III.

Renal function after preeclampsia: a longitudinal pilot study.

BACKGROUND: Women with a history of preeclampsia are at increased risk to develop end-stage renal disease. In this longitudinal study, we evaluated renal function in women with a history of severe preeclampsia and parous controls over a period of 14 years. METHODS: Renal function was measured 1 and then 14 years postpartum by para-aminohippurate and inulin clearances in 20 women with a history of severe preeclampsia and 8 parous controls. RESULTS: The difference in glomerular filtration rate 1 year postpartum between women with a history of preeclampsia and parous controls (112 ± 10 and 125 ± 8 ml/min/1.73 m(2), p < 0.01) had disappeared 14 years postpartum (104 ± 10 and 109 ± 13 ml/min/1.73 m(2), p = 0.37). There was a consistent trend for a lower effective renal plasma flow both 1 and 14 years postpartum (477 ± 90 and 543 ± 92, p = 0.09 and 473 ± 85 and 543 ± 98 ml/min/1.73 m(2), p = 0.07). CONCLUSIONS: This explorative study suggests no accelerated renal function loss in the first decade after preeclampsia.

Markers of cardiovascular disease risk after hypertension in pregnancy.

OBJECTIVES: Women with a history of preeclampsia or gestational hypertension have an increased risk of cardiovascular disease. Underlying cardiovascular risk factors, persistent endothelial dysfunction or sympathetic overactivity may contribute to this risk. We studied markers of cardiovascular disease risk in nonpregnant women with a history of hypertension in pregnancy. METHODS: Women with a history of preeclampsia (n = 39), gestational hypertension (n = 27) and normal pregnancies (n = 35) were studied 2-12 years after delivery. Laboratory measures included plasma fasting lipids, glucose, insulin, creatinine and urinary albumin-to-creatinine ratio. Blood pressure was measured by 24-h ambulatory blood pressure monitoring, endothelial function by flow-mediated dilatation and sympathetic activity by both head-up tilt test and cold pressor test, including the response of the circulating renin-angiotensin system to tilt testing. RESULTS: Compared with women who had previous normal pregnancies, women with a history of preeclampsia or gestational hypertension have higher ambulatory blood pressure, BMI and relative insulin resistance. Glomerular filtration rate, albumin-to-creatinine ratio, endothelial function and sympathetic activity was similar among the three groups. CONCLUSION: Women with a history of preeclampsia or gestational hypertension have features of the metabolic syndrome which are presumably present already before pregnancy, predisposing them to hypertensive disorders of pregnancy and later cardiovascular risk. In this study, we found no evidence for early renal damage, endothelial dysfunction or sympathetic overactivity in the postpartum state.

Pregnancy reduces the accuracy of the estimated glomerular filtration rate based on Cockroft-Gault and MDRD formulas.

OBJECTIVE: This study aims to determine the effect of pregnancy on the accuracy of 3 commonly used methods to estimate glomerular filtration rate ([GFR] creatinine clearance, the Cockroft-Gault, and modification of diet in renal disease [MDRD] formulas) using the inulin clearance as a reference. DESIGN: Longitudinal study design. SETTING: University hospital. POPULATION: A total of 44 parous nonsmoking Caucasian women. They had a history of uneventful pregnancy (n = 9), preeclampsia (n = 27), and intrauterine fetal demise (n = 8). METHODS: Measurements were performed both in pre-pregnancy and early pregnancy (8 weeks of gestation) and included inulin infusion, blood pressure, and 24-hour urinary and serum creatinine. Agreement between methods to estimate GFR was assessed by the Bland and Altman method. MAIN OUTCOME MEASURES: GFR estimated by inulin and creatinine clearances and the Cockroft-Gault and MDRD formulas. RESULTS: During early pregnancy, the GFR measured by inulin increased 32% compared with the pre-pregnant value (from 115 ± 18 to 150 ± 23 mL/min·1.73 m(-2)), whilst the GFR measured by the indirect methods only increased 20%. The observed bias and limits of agreements are larger in early pregnancy relative to the pre-pregnant state for all 3 methods. CONCLUSION: The renal hyperfiltration during pregnancy decreases further the accuracy of the creatinine clearance and the Cockroft-Gault and MDRD formulas to estimate GFR.

Insulin resistance relates to microvascular reactivity 23 years after preeclampsia.

Preeclampsia, an endothelial disorder of pregnancy, is associated with an increased risk on cardiovascular diseases. Cardiovascular risk factors may mediate vascular dysfunction both during pregnancy but also later in life. This study aims to investigate microvascular reactivity, and its relationship with several cardiovascular risk factors, in women with a history of preeclampsia and controls. In this cross-sectional study we compared women with a history of preeclampsia (PE, n=22) with women with uneventful pregnancies only (CON, n=29) 23 years after their first delivery. Participants were matched for BMI, age and date of delivery. We assessed blood concentrations of fasting glucose, HbA1c, insulin, (total, HDL-, LDL-) cholesterol, triglycerides and CRP. Endothelial function was assessed by measurement of skin microcirculatory blood flow by Laser Doppler flowmetry at the dorsal and ventral site of the finger during post-occlusive reactive hyperemia (PORH). PE had higher fasting insulin levels and HOMA-IR compared with CON. The PORH response was similar in both groups. The area under the curve of PORH correlated with insulin and HOMA-IR at both sites, with BMI, triglycerides at the dorsal site and with CRP at the ventral site of the finger in PE and not in CON. In conclusion, 23 years after pregnancy we did not observe a difference in the microvascular hyperemic response between women with a history of preeclampsia and controls. Meanwhile, the results of our study suggest that insulin resistance and other cardiovascular risk factors are related to microvascular reactivity in middle-aged women with a history of preeclampsia.

Reduced renal function after preeclampsia does not result from accelerated age-dependent renal function loss.

Preeclampsia is associated with later kidney disease. This study tested the hypothesis that the normal decline in renal function with age is more rapid in formerly preeclamptic women than in controls. Four groups were compared cross-sectionally: young women with a history of preeclampsia (n = 34), young controls (n = 12), middle-aged women with a history of preeclampsia (n = 22) and middle-aged controls (n = 29). We measured blood pressure (semi-automatic device), effective renal plasma flow (ERPF, para-aminohippurate clearance), glomerular filtration rate (GFR, creatinine clearance) and cardiac output (Doppler echocardiography). ERPF was lower in both young and middle-aged women with a history of preeclampsia relative to controls. The decrease in both GFR and ERPF with age was comparable in both groups. In conclusion, the lower renal function in middle-aged formerly preeclamptic women does not result from accelerated age-dependent renal function loss, but from an already reduced renal function relative to parous controls at young age.

Remote hemodynamics and renal function in formerly preeclamptic women.

OBJECTIVE: Women with a history of preeclampsia have an increased risk of developing chronic hypertension and cardiovascular disease. However, little is known about the mechanism responsible for vascular disease in formerly preeclamptic women. The aim of our study was to test whether preeclampsia predisposes to central hemodynamic and renal impairments 20 years after pregnancy. METHODS: In this cross-sectional study, 22 formerly preeclamptic women and 29 parous controls participated, matched for body mass index, age, and date of birth. All women delivered in the period of 1979-1987. Measures included automated blood pressure, Doppler echocardiography, microalbuminuria, paraaminohippurate, and creatinine clearances. Hypertension was defined as blood pressure at or above 140/90 mm Hg, using antihypertensive drugs, or both. RESULTS: Hypertension was present in 55% of the formerly preeclamptic women and 7% of the women in the control group (P<.01). Mean arterial pressure was higher in the formerly preeclamptic women compared with those in the control group (100 and 88 mm Hg, respectively, P<.01). Peripheral vascular resistance was about 20% higher, renal vascular resistance about 30% higher, and renal blood flow about 15% lower in the formerly preeclamptic women compared with those in the control group (P<.05). Similar results were observed after stratification for hypertension in both groups. CONCLUSION: Both normotensive and hypertensive middle-aged, formerly preeclamptic women showed impaired central hemodynamic and renal function compared with parous controls. LEVEL OF EVIDENCE: II.