High-sensitivity cardiac troponin I in women with a history of early-onset preeclampsia.

OBJECTIVE: Preeclampsia is associated with an elevated risk of cardiovascular disease later in life. Women with a history of preeclampsia are at risk of developing hypertension as well as ischemic heart disease. Identification of women at the highest risk is important to initiate preventive strategies. We investigated whether high-sensitivity cardiac troponin I (hs-cTnI) levels are associated with a history of early-onset preeclampsia, and with hypertension in these high-risk women. METHODS: Approximately 9-10 years after pregnancy, hs-cTnI levels were measured for 339 women of the Preeclampsia Risk Evaluation in FEMales cohort, consisting of 177 women with a history of early-onset preeclampsia and 162 women with a previous uncomplicated index pregnancy. Associations were analyzed using several statistical tests and linear regression analysis. RESULTS: The median hs-cTnI levels (IQR) were 2.50 ng/l (2.30) in women with a history of early-onset preeclampsia and 2.35 ng/l (2.50) in women without a history of preeclampsia, P = 0.53. Among women with a history of early-onset preeclampsia, the hs-cTnI levels were higher in women who were hypertensive compared with their normotensive counterparts (medians 2.60 versus 2.30; P = 0.03). In addition, blood pressure levels increased with increasing hs-cTnI levels. CONCLUSION: We did not find a difference in hs-cTnI levels between women with and without a history of early-onset preeclampsia. Nonetheless, hs-cTnI levels were statistically significantly higher in current hypertensive women with a history of preeclampsia compared with their normotensive counterparts. Therefore, hs-cTnI levels might improve risk prediction for women at the highest risk of cardiovascular disease.

Regulatory antibodies against GPCR in women ten years after early-onset preeclampsia.

Preeclampsia is associated with an increased cardiovascular risk later in life. Anti-GPCR autoantibodies have been shown to contribute to the development of cardiovascular disease. We investigated whether anti-GPCR autoantibodies are elevated in women with a history of early-onset preeclampsia 8-11 years postpartum, and whether they correlate with clinical outcomes. We investigated data from the Preeclampsia Risk EValuation in FEMales cohort, a retrospective matched case-control study. Anti AT1R-, beta1AR-, ETAR-, PAR1- and CXCR3- autoantibodies were determined in 485 samples by using commercially available ELISA. Women with the lowest combined levels of autoantibodies and a history of early preeclampsia had significantly higher SBP, DBP and MAP (all p<0.001) compared to the controls. The individual titer levels of autoantibodies were not different between controls and former early PE groups 8-11 years postpartum. In conclusion, regulatory autoantibodies alone are not sufficient to explain hypertension or other cardiovascular pathologic conditions, but together with other risk factors such as a previous hypertensive pregnancy, lower levels of autoantibodies are associated with increased blood pressure.

High-Normal Estimated Glomerular Filtration Rate in Early-Onset Preeclamptic Women 10 Years Postpartum.

Women with a history of preeclampsia have a 5- to 12-fold increased risk to develop end-stage kidney disease. Previous observations in small cohorts suggest that former preeclamptic (fPE) women have subtle abnormalities in renal hemodynamics and renal function, which might predispose them to renal failure in later life. In this study, we analyzed renal function in a cross-sectional cohort consisting of former early-onset preeclamptic (fPE, n=339) and former healthy pregnant women (fHP, n=332), overall with a mean age of 39 years at 10 years postpartum. Estimated glomerular filtration rate (eGFR), assessed by the modification of diet in renal disease (MDRD) and chronic kidney disease-epidemiology (CKD-epi) equations, and urinary protein:creatinine ratios were assessed 10 years postpartum. Median MDRD and CKD-epi eGFR did not significantly differ between fHP and fPE groups, whereas a comparison of distribution of eGFR revealed a shift toward a high-normal MDRD eGFR in the fPE group (χ2, P=0.02) with the same trend for CKD-epi eGFR (χ2, P=0.18). The odds ratio for fPE women having MDRD eGFR >110 mL/min per 1.73 m2 was 1.6 (1.1-2.4). In addition, the median urinary protein:creatinine ratio was slightly higher in fPE (8.5 versus 7.1 mg/mmol; P<0.01) and correlated positively with both MDRD and CKD-epi eGFR in fPE women. No increased incidence of CKD in fPE women was observed. In conclusion, we demonstrate subtle changes in renal function in former early-onset preeclamptic women 10 years postpartum, characterized by a high-normal eGFR and a slightly higher protein excretion. Whether these subtle differences predispose to or predict long-term renal function loss in fPE women remains to be investigated. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR2668.

Long-term follow-up of psychosocial distress after early onset preeclampsia: the Preeclampsia Risk EValuation in FEMales cohort study.

OBJECTIVE: To examine long-term psychosocial distress in women with a history of early onset preeclampsia (PE) compared to a comparison group. METHODS: Women with and without a history of early onset PE participating in the 'Preeclampsia Risk EValuation in FEMales' (PREVFEM) study were sent questionnaires, on average 14.1 years (SD = 3.2, range 5-23 years) after the index pregnancy. In total 265 (77%) women with PE and 268 (78%) age-matched women without PE returned questionnaires (mean age 43.5, SD =4.6 years). Group differences were examined on indicators of psychosocial distress, depressive symptoms, anxiety, fatigue, loneliness, marital quality, trait optimism and Type D personality, and unadjusted and adjusted for a priori chosen and study-specific covariates. In secondary analyses, the effect of previously detected hypertension was examined, as well as pregnancy-related events within the PE group. RESULTS: Women with a history of PE reported more subsequent depressive symptoms (B = 0.70, 95% CI 0.09-1.32, p = 0.026) and more fatigue (B = 1.12, 95% CI 0.07-2.18, p = 0.037) compared to the non-PE group, but the differences explained less than 1% of the variance. The differences remained after adjustment for age, BMI and education level, and additional adjustment for partner, being unemployed and physical activity. No significant differences were observed for anxiety, loneliness, marital quality, optimism, or Type D personality. These differences were not explained by four-year previously measured elevated blood pressure in the PE group. Having had a stillborn child or early neonatal death during the index pregnancy was associated with higher depressive symptoms, anxiety, fatigue, and loneliness in the PE group, but these factors explained only a small proportion of the variance in these psychosocial distress factors. CONCLUSION: A history of early PE is associated with slightly higher levels of depressive symptoms and fatigue on average 14 years later, but this is unlikely to be of clinical relevance.

Novel cardiovascular biomarkers in women with a history of early preeclampsia.

OBJECTIVE: Women with a history of preeclampsia are at increased risk for future cardiovascular disease. Determination of cardiovascular biomarkers may be useful to understand the pathophysiological mechanism of cardiovascular disease development in these women. METHODS: We performed an analysis in the Preeclampsia Risk EValuation in FEMales study, a retrospective cohort consisting of 339 women with a history of early preeclampsia and 332 women after normotensive pregnancy. Women attended a follow-up visit ten years after the index pregnancy. A subset of 8 different cardiovascular biomarkers was investigated, reflecting inflammatory, metabolic, thrombotic and endothelial function markers. Associations between PE and these novel biomarkers were analyzed by linear regression analysis and adjusted for traditional cardiovascular risk factors. RESULTS: Mean age of 671 women of the PREVFEM cohort was 39 years and women were on average 10 years post index pregnancy. Women post preeclampsia had significantly higher levels of SE-selectin (adjusted difference 4.55, 99%CI 0.37; 8.74) and PAPPA (adjusted difference 19.08; 99%CI 13.18; 24.99), whereas ApoB (adjusted difference -0.23 99%CI -0.32; -0.14) was inversely associated with preeclampsia, compared to women with a previous normotensive pregnancy. Adiponectin, leptin, sICAM-1, sVCAM-1 and PAI-1 were not different between both groups. CONCLUSION: We demonstrated an independent association of preeclampsia with SE-selectin and PAPPA (markers of vascular dysfunction), which may contribute to future cardiovascular events in women post preeclampsia. However, ApoB (an apolipoprotein) was significantly lower and could point at a protective mechanism in our PE study women.

More vasomotor symptoms in menopause among women with a history of hypertensive pregnancy diseases compared with women with normotensive pregnancies.

OBJECTIVE: Cardiovascular disease is the major cause of mortality in women worldwide. In recent years, several female-specific cardiovascular risk factors, such as hypertensive pregnancy diseases (HPDs) and vasomotor menopausal symptoms (VMS), have been identified. In this study, we evaluated the association between a history of HPD and the presence of VMS. METHODS: We consecutively included 853 women (mean age, 55.5 y) who visited the outpatient cardiovascular clinic for women in Kampen between 2003 and 2010. The visit included a questionnaire on history of HPD, demographic characteristics, and VMS; physical examination; and blood sampling. Logistic regression analysis was used to analyze the data. RESULTS: A history of HPD was reported by 274 women (32%), and VMS were reported by 83% of women with a history of HPD and by 75% of women without a history of HPD. In adjusted models, VMS were more often present (odds ratio [OR], 1.62; 95% CI, 1.00-2.63) and more frequently persisted for longer than 1 year (OR, 2.05; 95% CI, 1.08-3.89) among women with a history of HPD than among women with normotensive pregnancies. VMS were more often severe in women with a history of HPD, but this did not reach significance (adjusted OR, 1.28; 95% CI, 0.92-1.80). The frequency and intensity of VMS did not differ between both groups. CONCLUSIONS: In our "Kampen women cardiology clinic" cohort, women with a history of HPD report VMS during the menopausal transition significantly more often than women with normotensive pregnancies.

Electrocardiographic parameters in women ten years post-early preeclampsia.

OBJECTIVE: Women with a history of preeclampsia are at increased risk to develop cardiovascular disease (CVD) later in life, especially hypertension is common. In this study we aimed to evaluate electrocardiographic parameters as a proxy for detrimental hypertensive effects and later CVD. METHODS: The Preeclampsia Risk EValuation study in FEMales (PREVFEM) study is a prospective cohort study consisting of 339 women with a history of early onset preeclampsia (EOP) and 332 age-matched women without a history if EOP as reference. At ten years post index pregnancy a 12-lead electrocardiogram recording was made. RESULTS: There were no significant differences in ECG parameters between both groups at 3 9years of age. In our cohort of young women SBP (OR(mmHg): 1.04; 95% CI: 1.2-1.06) as well as DBP (OR(mmHg): 1.04; 95% CI: 1.01-1.07) and stage 2 hypertension (OR: 3.35; 95% CI: 1.16-9.63) were significantly associated with ECG criteria for LVH, but not for other ECG abnormalities. EOP gives no significant adjusted risk on ECG abnormalities compared to women without EOP. CONCLUSION: EOP is no significant predictor of non-specific ECG abnormalities. Routine ECG screening in young women after preeclampsia is not recommended in non-hypertensive women, but may be useful when hypertension is present.

Cardiovascular risk factors in women 10 years post early preeclampsia: the Preeclampsia Risk EValuation in FEMales study (PREVFEM).

INTRODUCTION: Preeclampsia is a complication of pregnancy and a known risk factor for cardiovascular disease (CVD) later in a women's life. The best approach for prevention of CVD in affected young women is yet unclear. We sought to investigate the prevalence of cardiovascular risk factors in women at 10 years post preeclampsia in comparison with a reference group. METHODS: Women with a history of early preeclampsia (exposed), DBP ≥ 90 mmHg with proteinuria ≥ 0.3 gram/24 h before 32 weeks of gestation, and an equal number of women after uncomplicated pregnancy (non-exposed) from the obstetric database of 1991-2007, were sent a questionnaire and invited for a cardiovascular screening programme. RESULTS: The current study included 339 exposed women and 332 non-exposed women, 10 years post index-pregnancy. Systolic and diastolic blood pressures (SBP/DBP) were 127/86 mmHg versus 119/79 mmHg in the exposed and reference group respectively (p < 0.001). Exposure to early preeclampsia was associated with a threefold increased prevalence of hypertension (adjusted odds ratio (OR) 3.59, 95%CI 2.48-5.20). BMI and waist circumference were 26.9 kg/m(2) and 86.5 cm in the exposed group and 26.2 kg/m(2) (p = 0.07) and 83 cm (p = 0.001) in the non-exposed group. We found no differences in levels of glucose, lipids and CRP. Adjusted OR for the metabolic syndrome in women post preeclampsia was 2.18 (95% CI 1.34-3.52) compared with women in the reference group. CONCLUSION: We found a high prevalence of hypertension in young women at 10 years post early preeclampsia. More research on the timing of cardiovascular screening in these high-risk women is needed.

Preeclampsia as a female-specific risk factor for chronic hypertension.

Preeclampsia is a complication of pregnancy that has also long term effects on maternal health. Several epidemiologic studies have shown an increased risk for cardiovascular morbidity (relative risk [RR] 2.3) and mortality (RR 2.3) in women after a history of preeclampsia. The chance to develop chronic hypertension afterwards is twofold to 10 times higher in affected women, compared with women after normotensive pregnancies. As hypertension is a major cardiovascular risk factor, early detection and treatment is mandatory to reduce the risk of future cardiovascular disease. Data on (cost)-effectiveness of cardiovascular screening programs in women after preeclampsia are currently lacking and there are no recommendations yet for prevention in the guidelines. We recommend regularly preventive blood pressure measurements after high risk pregnancies. More research is needed to identify women who will profit most of early intervention.

Implementation and evaluation of a nurse-centered computerized potassium regulation protocol in the intensive care unit--a before and after analysis.

BACKGROUND: Potassium disorders can cause major complications and must be avoided in critically ill patients. Regulation of potassium in the intensive care unit (ICU) requires potassium administration with frequent blood potassium measurements and subsequent adjustments of the amount of potassium administrated. The use of a potassium replacement protocol can improve potassium regulation. For safety and efficiency, computerized protocols appear to be superior over paper protocols. The aim of this study was to evaluate if a computerized potassium regulation protocol in the ICU improved potassium regulation. METHODS: In our surgical ICU (12 beds) and cardiothoracic ICU (14 beds) at a tertiary academic center, we implemented a nurse-centered computerized potassium protocol integrated with the pre-existent glucose control program called GRIP (Glucose Regulation in Intensive Care patients). Before implementation of the computerized protocol, potassium replacement was physician-driven. Potassium was delivered continuously either by central venous catheter or by gastric, duodenal or jejunal tube. After every potassium measurement, nurses received a recommendation for the potassium administration rate and the time to the next measurement. In this before-after study we evaluated potassium regulation with GRIP. The attitude of the nursing staff towards potassium regulation with computer support was measured with questionnaires. RESULTS: The patient cohort consisted of 775 patients before and 1435 after the implementation of computerized potassium control. The number of patients with hypokalemia (<3.5 mmol/L) and hyperkalemia (>5.0 mmol/L) were recorded, as well as the time course of potassium levels after ICU admission. The incidence of hypokalemia and hyperkalemia was calculated. Median potassium-levels were similar in both study periods, but the level of potassium control improved: the incidence of hypokalemia decreased from 2.4% to 1.7% (P < 0.001) and hyperkalemia from 7.4% to 4.8% (P < 0.001). Nurses indicated that they considered computerized potassium control an improvement over previous practice. CONCLUSIONS: Computerized potassium control, integrated with the nurse-centered GRIP program for glucose regulation, is effective and reduces the prevalence of hypo- and hyperkalemia in the ICU compared with physician-driven potassium regulation.

The impact of a reduced dose of dexamethasone on glucose control after coronary artery bypass surgery.

BACKGROUND: Intensive insulin therapy to maintain normoglycemia after cardiac surgery reduces morbidity and mortality. We investigated the magnitude and duration of hyperglycemia caused by dexamethasone administered after cardiopulmonary bypass. METHODS: A single-center before-after cohort study was performed. All consecutive patients undergoing coronary artery bypass grafting with cardiopulmonary bypass during a 6-month period were included. Insulin administration was guided by a sliding scale protocol. Halfway the observation period, the dexamethasone protocol was changed. The single dose (1D) group received a pre-operative dose of dexamethasone of 1 mg/kg. The double dose group (2D) received an additional dose of 0.5 mg/kg of dexamethasone post-operatively at ICU admission. RESULTS: We included 116 patients in the 1D group and 158 patients in the 2D group. There were no significant baseline differences between the groups. Median Euroscore was 5. In univariable analysis, the glucose level was different between groups 1D and 2D at 4, 6, 9, 12 and 24 hours after ICU admission (all p < 0.001). Insulin infusion was higher in the 1D group. Corrected for insulin dose in multivariable linear analysis, the difference in glucose between the 1D and 2D groups was 1.5 mmol/L (95% confidence interval 1.0-2.0, p < 0.001) 12 hours after ICU admission. CONCLUSION: Dexamethasone exerts a hyperglycemic effect in cardiac surgery patients. Patients receiving high-dose corticosteroid therapy should be monitored and treated more intensively for hyperglycemic episodes.