Impact of body mass index on markers of vascular health in normotensive women with history of pre-eclampsia.

OBJECTIVE: Obesity and pre-eclampsia (PE) are both associated with vascular dysfunction, which translates into an increased risk for cardiovascular disease in later life. The aim of this study was to investigate whether there is an interaction between body mass index (BMI) and a history of PE in their effects on vascular health. METHODS: This was an observational case-control study of 30 women with a history of PE who were compared with 31 age- and BMI-matched controls who had an uncomplicated pregnancy. Flow-mediated dilation (FMD), carotid intima-media thickness (cIMT) and carotid distensibility (CD) were measured 6-12 months postpartum. To evaluate the impact of physical fitness, maximum oxygen uptake capacity was assessed using a standardized maximum exhaustion cycling test using breath-by-breath analysis. To specify further BMI subgroups, metabolic syndrome constituents were assessed in all individuals. RESULTS: Formerly pre-eclamptic women had significantly lower FMD (5.1 ± 2.1% vs 9.4 ± 3.4%; P < 0.01), higher cIMT (0.59 ± 0.09 vs 0.49 ± 0.07 µm; P < 0.01) and lower CD (1.54 ± 0.37%/10 mmHg vs 1.80 ± 0.39%/10 mmHg; P < 0.01) compared with controls. In our study, population BMI correlated negatively with FMD (P = 0.04) but not with cIMT or CD. BMI and PE did not exhibit an interaction effect on these vascular parameters. Physical fitness was lower in women with a history of PE and in women with higher BMI. Constituents of the metabolic syndrome, including insulin, homeostasis model assessment for insulin resistance (HOMA-ir), triglyceride, microalbuminuria and systolic and diastolic blood pressure, were significantly higher in formerly pre-eclamptic women. BMI affected glucose metabolism but not lipids or blood pressure. BMI and PE positively interacted in their effect on insulin (P = 0.04) and HOMA-ir (P = 0.02). CONCLUSIONS: Both BMI and a history of PE have negative effects on endothelial function, insulin resistance and physical fitness. In formerly pre-eclamptic women, the effect of BMI on insulin resistance was particularly high, suggesting a synergistic effect. Additionally, independently of BMI, a history of PE was associated with reduced FMD and CD and increased cIMT and blood pressure. Recognizing the cardiovascular risk profile is important for informing patients and encouraging targeted lifestyle modifications. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Venous and autonomic function in formerly pre-eclamptic women and controls matched for body mass index.

OBJECTIVE: Prepregnancy reduced plasma volume (PV) increases the risk of subsequent pre-eclamptic pregnancy. Reduced PV is thought to reflect venous reserve capacity, especially when venous vasculature is constricted and sympathetic tone is elevated. As obesity might affect these variables, and is associated with pre-eclampsia, increased body weight may underlie these observations. The aim of this study was to determine whether the relationship between reduced venous reserve and pre-eclampsia is independent of body mass index (BMI). METHODS: This was an observational case-control study in which venous reserve capacity in 30 formerly pre-eclamptic, but currently non-pregnant, women divided equally into three groups based on BMI (BMI 19.5-24.9, 25.0-29.9 or ≥ 30.0 kg/m2 ), was compared with that in 30 healthy parous, non-pregnant controls. Cases and controls were matched for BMI, age and parity. Venous reserve capacity was quantified by assessing PV and venous compliance (VeC). The autonomic nervous system regulating venous capacitance was evaluated using heart rate (HR) variability analysis, with the women in a resting supine position and during positive head-up tilt (HUT). RESULTS: Compared with controls, formerly pre-eclamptic women had, when in a resting supine position, lower PV (1339 ± 79 vs 1547 ± 139 mL/m2 (P < 0.0001)), lower VeC (0.04 ± 0.02 vs 0.07 ± 0.02 mL/dL/mmHg (P < 0.0001)), higher sympathetic tone (1.9 ± 1.1 vs 1.2 ± 0.7 (P = 0.002)) and lower baroreceptor sensitivity (BRS; 8.7 ± 3.8 vs 19.0 ± 1.7 ms/mmHg (P < 0.0001)). During HUT, women with a history of pre-eclampsia had less modulatory capacity over VeC and BRS, while HR and sympathetic tone remained consistently higher. CONCLUSIONS: Women with a history of pre-eclampsia had reduced venous reserve capacity compared with that in BMI-matched controls. This is reflected by lower PV and VeC, with the autonomic balance being shifted towards sympathetic dominance and lower BRS. This suggests that underlying reduced venous reserve, but not BMI, relates to pre-eclampsia. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Decreased endothelial function and increased subclinical heart failure in women several years after pre-eclampsia.

OBJECTIVES: Pre-eclampsia (PE) is associated with both postpartum endothelial dysfunction and asymptomatic structural heart alterations consistent with heart failure Stage B (HF-B). In this study, we assessed the relationship between endothelial function, measured by flow-mediated dilation (FMD), and HF-B in women with a history of PE. METHODS: This was an observational study in which 67 formerly pre-eclamptic women (≥ 4 years postpartum) and 37 healthy parous controls were assessed ultrasonographically for cardiac function and geometry, as well as for endothelial function by means of brachial artery FMD. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) > 95 g/m2 ), concentric remodeling (relative wall thickness > 0.42 and LVMi ≤ 95 g/m2 ), mild systolic dysfunction (left ventricular ejection fraction > 40% and < 55%) or asymptomatic valvular disease. Cardiovascular and metabolic syndrome variables were compared between women with history of PE and controls, as well as between those in the formerly pre-eclamptic group who had HF Stage A, HF-B or no HF. Logistic regression analysis was performed to assess the associations of FMD with PE, metabolic syndrome risk factors and obstetric parameters. RESULTS: The prevalence of HF-B amongst formerly pre-eclamptic women was three-fold higher than that observed for controls (25% vs 8%, P < 0.05), while FMD was lower in formerly pre-eclamptic women compared with controls (6.12% vs 8.22%, P < 0.01); history of PE remained associated independently with lower FMD after adjusting for metabolic syndrome risk factors and obstetric parameters (ß, -1.88; 95% CI, -3.59 to -0.18). However, HF-B did not relate to low FMD in formerly pre-eclamptic women. CONCLUSIONS: Years after pregnancy, formerly pre- eclamptic women have lower FMD and have HF-B more often compared with healthy parous controls. Nonetheless, HF-B was not related to reduced FMD. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prevalence of asymptomatic heart failure in formerly pre-eclamptic women: a cohort study.

OBJECTIVES: After pre-eclampsia (PE), the prevalence of structural heart disease without symptoms, i.e. heart failure Stage B (HF-B), may be as high as one in four women in the first year postpartum. We hypothesize that a significant number of formerly pre-eclamptic women with HF-B postpartum are still in their resolving period and will not have HF-B during follow-up. METHODS: In this prospective longitudinal cohort study, we included 69 formerly pre-eclamptic women who underwent serial echocardiographic measurements at 1 and 4 years postpartum. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) > 95 g/m2 ), concentric remodeling (relative wall thickness > 0.42 and LVMi ≤ 95 g/m2 ), mild systolic dysfunction (left ventricular ejection fraction > 40% and < 55%) or asymptomatic valvular disease. Women were subdivided and analyzed according to HF-B outcome: no HF-B at either visit; HF-B at first visit only; HF-B at second visit only; HF-B at both visits. RESULTS: The prevalence of HF-B in formerly pre-eclamptic women was 23% in the first year postpartum and 23% after 4 years. At the second visit, HF-B had resolved in 62.5% of affected women but was newly developed in 19% of initially unaffected women. At the first visit, 56% of women diagnosed with HF-B had reduced systolic function whereas at the second visit 69% of women with HF-B had concentric remodeling with mostly normal ejection fraction, consistent with diastolic dysfunction. CONCLUSIONS: The prevalence of HF-B can be considered consistently high (1 in 4) amongst formerly pre-eclamptic women at follow-up. Nonetheless, at an individual level, more than 60% of women found initially to be affected by HF-B will recover, whilst about 20% of formerly pre-eclamptic women with normal echocardiography in the first year postpartum will develop HF-B over the following years. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Pre-eclampsia: an important risk factor for asymptomatic heart failure.

OBJECTIVES: Pre-eclampsia (PE) is associated with both postpartum structural asymptomatic heart disease (i.e. heart failure Stage B (HF-B)) and conventional cardiovascular (CV) risk factors. We aimed to evaluate the extent to which PE, adjusted for conventional CV risk factors, is associated independently with asymptomatic cardiac abnormalities postpartum. METHODS: In this cross-sectional cohort study, 107 formerly pre-eclamptic women and 41 women with uneventful previous pregnancy (controls) were invited for CV risk assessment 4-10 years postpartum. This included cardiac ultrasound, blood pressure (BP) measurement and evaluation of metabolic syndrome determinants. Asymptomatic structural and functional cardiac abnormalities were classified as HF-B, according to the American Heart Association guidelines. Prehypertension was defined as systolic BP of 120-139 mmHg and/or diastolic BP of 80-89 mmHg. Univariate and multivariate regression analyses were performed to calculate associations of PE and conventional risk factors with HF-B. RESULTS: The prevalence of asymptomatic HF-B was approximately 3.5-fold higher in the PE group compared with controls (25% vs 7%, P < 0.01); 67% of this group had concentric remodeling and 22% had mildly impaired ejection fraction. After adjustment for postpartum interval, hypertension and high-density lipoprotein, PE was significantly associated with HF-B (adjusted odds ratio, 4.4 (95% CI, 1.0-19.1)). Moreover, in the formerly pre-eclamptic group, prehypertension was associated significantly with HF-B (odds ratio, 4.3 (95% CI, 1.4-12.7)), while metabolic syndrome determinants were not. CONCLUSION: PE is associated with a four-fold increased female-specific risk of asymptomatic cardiac abnormalities. Prehypertension apparently increases this risk significantly, while metabolic syndrome determinants do not. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Recurrent pre-eclampsia in women with metabolic syndrome and low plasma volume: a retrospective cohort study.

OBJECTIVE: To determine the prevalence of recurrent pre-eclampsia in women with a history of pre-eclampsia with both metabolic syndrome and low plasma volume postpartum, as compared with women without either entity. DESIGN: Retrospective cohort study. SETTING: Three tertiary referral hospitals in the Netherlands. POPULATION: Women with a history of pre-eclampsia. METHODS: In 196 women with a history of pre-eclampsia we determined the presence or absence of metabolic syndrome using the World Health Organization criteria and measured plasma volume with the (125) I-human serum albumin indicator dilution technique. We compared the prevalence of recurrent pre-eclampsia in four groups, classified according to presence or absence of metabolic syndrome and low or normal plasma volume, calculating odds ratios (OR), adjusted for confounders. MAIN OUTCOME MEASURE: Recurrence of pre-eclampsia in the subsequent pregnancy. RESULTS: The prevalence of recurrent pre-eclampsia was 12% (12/99) in women without metabolic syndrome with normal plasma volume, versus 47% (8/17) in women with both metabolic syndrome and low plasma volume: OR 6.44 (95% CI 2.09-19.90), adjusted OR 7.90 (95% CI 2.30-27.16). Recurrent pre-eclampsia was present in 44% (10/23) and 25% (14/57) of women with isolated metabolic syndrome and low plasma volume, respectively. CONCLUSIONS: In the concomitant presence of metabolic syndrome and low plasma volume, the prevalence of recurrent pre-eclampsia was nearly 50%, which is four times as high as the prevalence in women without either entity. TWEETABLE ABSTRACT: Metabolic syndrome and low plasma volume raise the risk of recurrent pre-eclampsia to nearly 50%.

Cardiovascular disease risk is only elevated in hypertensive, formerly preeclamptic women.

OBJECTIVE: To analyse the predicted 10- and 30-year risk scores for cardiovascular disease (CVD) in patients who experienced preeclampsia (PE) 5-10 years previously compared with healthy parous controls. DESIGN: Observational study. SETTING: Tertiary referral hospital in the Netherlands. POPULATION: One hundred and fifteen patients with a history of PE and 50 controls. PE patients were categorised into two groups, hypertensive (n = 21) and normotensive (n = 94), based on use of antihypertensive medication, and next categorised into subgroups based on the onset of PE: early-onset PE (n = 39) and late-onset PE (n = 76). METHODS: All participants underwent cardiovascular risk screening 5-10 years after index pregnancy. We measured body mass, height and blood pressure. Blood was analysed for fasting glucose, insulin and lipid levels. All participants completed a validated questionnaire. The 10- and 30-year Framingham risk scores were calculated and compared. MAIN OUTCOME MEASURES: Estimated Framingham 10- and 30-year risk scores for CVD. RESULTS: The overall 10- and 30-year CVD median risks weighing subjects' lipids were comparable between formerly PE women and controls; 1.6 versus 1.5% (P = 0.22) and 9.0 versus 9.0% (P = 0.49), respectively. However, hypertensive formerly PE women have twice the CVD risk as normotensive formerly PE women: 10- and 30-year CVD median risks were 3.1 versus 1.5% (P < 0.01) and 19.0% versus 8.0% (P < 0.01), respectively. Risk estimates based on BMI rather than lipid profile show comparable results. Early-onset PE clustered more often in the hypertensive formerly PE group and showed significantly higher 10- and 30-year CVD risk estimates based on lipids compared with the late-onset PE group: 1.7 versus 1.3% (P < 0.05) and 10.0 versus 7.0% (P < 0.05), respectively. CONCLUSIONS: Women who are hypertensive after preeclampsia, have a twofold risk of developing CVD in the next 10-30 years. Formerly PE women who are normotensive in the first 10 years after their preeclamptic pregnancy have a comparable future cardiovascular risk to healthy controls.

Metabolic syndrome after pregnancies complicated by pre-eclampsia or small-for-gestational-age: a retrospective cohort.

OBJECTIVE: To study the prevalence of metabolic syndrome in women after a pregnancy complicated by pre-eclampsia or small-for-gestational-age (SGA), both epitomes of placental syndrome. DESIGN: A retrospective cohort study. SETTING: Single tertiary centre for maternal medicine in the Netherlands. POPULATION: Women with a history of pre-eclampsia in absence of SGA (n = 742) or pregnancy complicated by normotensive SGA (n = 147) between 1996 and 2010. METHODS: Women were routinely screened for underlying cardiometabolic and cardiovascular risk factors at least 6 months postpartum. Logistic regression analysis was used to calculate the odds ratio and adjusted odds ratio for each group. Adjustments were made for age, maternal height, smoking, parity, and interval between delivery and measurement. MAIN OUTCOME MEASURES: Prevalence of the metabolic syndrome. RESULTS: The prevalence of the metabolic syndrome in our population was two-fold higher for women with a history of pre-eclampsia (13.9%) compared with women with a history of SGA (7.6%). Calculated odds ratios for metabolic syndrome, fasting insulin, HOMA, and microalbuminuria were all higher for women with a history of pre-eclampsia compared with women with SGA. This difference persisted after adjustment for confounding factors: metabolic syndrome (adjusted odds ratio, aOR 2.11; 95% confidence interval, 95% CI 1.00-4.47) and hyperinsulinaemia (aOR 1.78; 95% CI 1.13-2.81) insulin resistance (HOMAIR ; aOR 1.80; 95% CI 1.14-2.86). Microalbuminuria (aOR 1.58; 95% CI 0.85-2.93) did not reach the level of significance after adjustment for confounding factors. CONCLUSIONS: A history of pre-eclampsia, rather than SGA, was associated with metabolic syndrome, suggesting that it relates to maternal rather than fetal etiology of placental syndrome.

Menstrual blood closely resembles the uterine immune micro-environment and is clearly distinct from peripheral blood.

STUDY QUESTION: Is menstrual blood a suitable source of endometrial derived lymphocytes? SUMMARY ANSWER: Mononuclear cells isolated from menstrual samples (menstrual blood mononuclear cells (MMC)) are clearly distinct from peripheral blood mononuclear cells (PBMC) and show a strong resemblance with biopsy-derived endometrial mononuclear cells. WHAT IS KNOWN ALREADY: A critical event in the onset of pregnancy is the implantation of the embryo in the uterine wall. The immune cell composition in the endometrium at the time of implantation is considered pivotal for success. Despite advancing knowledge on the composition of the immune cell population in the uterus, the role of endometrial immune cells in reproductive disorders is still not fully resolved, mainly due to the fact that this type of research requires invasive techniques. Here, we collected menstrual fluid and validated this unique non-invasive technique to obtain and study the endometrium-derived immune cells which would be present around the time of implantation. STUDY DESIGN, SIZE, DURATION: Five healthy non-pregnant females with regular menstruation cycles and not using oral contraceptives collected their menstrual blood using a menstrual cup in five consecutive cycles. Sampling took place over the first 3 days of menses, with 12 h intervals. Peripheral blood samples, taken before and after each menstruation, were obtained for comparative analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: MMC and PBMC samples were characterized for the different lymphocyte subsets by flow cytometry, with emphasis on NK cells and T cells. Next, the functional capacity of the MMC-derived NK cells was determined by measuring intracellular production of IFN-γ, granzyme B and perforin after culture in the presence of IL-2 and IL-15. MAIN RESULTS AND THE ROLE OF CHANCE: In support of their endometrial origin, MMC samples contained the typical composition of mononuclear cells expected of endometrial tissue, were phenotypically similar to the reported phenotype for biopsy-derived endometrial cells, and were distinct from PBMC. Increased percentages of NK cells and decreased percentages of T cells were found in MMC when compared with PBMC from the same female. The MMC-derived NK cells were pre-dominantly CD56(bright)/CD16(-), in contrast to the primarily CD56(dim)/CD16(+) peripheral blood NK cells. MMC-derived NK cells expressed CD103, indicating their mucosal origin. In addition, the pattern of natural cytotoxicity receptor (NCR) expression in MMC-derived NK cells was comparable with that in endometrial biopsy-derived NK cells. Compared with PBMC, the NKp30 expression was decreased, while the percentage of NKp44 positive cells was increased in MMC samples. CXCR3 and CXCR4 were hardly expressed by MMC-derived NK cells, indicating that these cells are not of PBMC origin. NK cells from MMC samples were functional as shown by their capacity to produce IFN-γ, granzyme B and perforin, upon stimulation with IL-2 and IL-15. MMC-derived T cells revealed an increased expression of CD103, CD69 and CXCR4 compared with PBMC-derived T cells. Importantly, MMC collection using a menstrual cup proved highly reliable and reproducible between women and between cycles. LIMITATIONS, REASONS FOR CAUTION: Based on the parameters we studied, MMC appear similar to biopsy-derived endometrial mononuclear cells. However, sampling is not done at the exact same time in the menstrual cycle, and thus we cannot exclude some, as yet undetected, differences. Also, it should be considered that for some women, the use of the menstrual cup may be unpleasant. WIDER IMPLICATIONS OF THE FINDINGS: Menstrual blood may be a source of endometrial cells and may create new opportunities to study uterine immunological cells in fertility issues. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for the present study. None of the authors have any conflict of interest to declare. TRIAL REGISTRATION NUMBER: NA.

Sex difference in fluid balance responses during prolonged exercise.

Maintaining a proper fluid balance is important during exercise as athletes are prone to develop dehydration during exercise. Although several factors may regulate the fluid balance, little is known about the role of sex during prolonged moderate-intensity exercise. Therefore, we compared body mass changes and fluid balance parameters in men vs women in a large heterogeneous group of participants during prolonged exercise. Ninety-eight volunteers walked 30-50 km at a self-selected pace. Exercise duration (8 h, 32 min) and intensity (69% HRmax) were comparable between groups. Men demonstrated a significantly larger change in body mass than women (-1.6% vs -0.9%, respectively, P < 0.001) and a higher incidence of dehydration (defined as ≥ 2% body mass loss) compared with women (34% vs 12%, respectively, odds ratio = 4.2, 95% CI = 1.1-16.7). Changes in blood sodium levels were significantly different between men (+1.5 mmol/L) and women (-0.4 mmol/L), while 27% of the men vs 0% of the women showed postexercise hypernatremia (sodium levels ≥ 145 mmol/L). Moreover, men demonstrated a significantly lower fluid intake (2.9 mL/kg/h) and higher fluid loss (5.0 mL/kg/h) compared with women (3.7 and 4.8 mL/kg/h, respectively). Taken together, our data suggest that men and women demonstrate different changes in fluid balance in response to a similar bout of exercise.

Quantitative ultrasonography of skeletal muscles in children: normal values.

The purpose of this study was to establish normal values of muscle thickness, ratio of muscle thickness to subcutaneous fat thickness, and muscle echo intensity in children between 11 weeks and 16 years of age. Transverse scans of four muscles were made by standardized real-time ultrasound examination. The scans were digitized, and mean echo intensity was measured using gray-scale analysis. A multiple regression equation was used to study which independent parameter (age, height, weight, or sex) influenced the variables for each muscle. Muscle thickness depended on the child's weight. The other parameters did not significantly influence muscle thickness after correction for weight. The ratio of muscle thickness to subcutaneous fat thickness depended on age. Echo intensity showed no correlation with either of the variables. As a result, all normal values, including the equation to calculate them, are described. These normal data may help to determine the diagnostic value of muscle ultrasound in children with suspected neuromuscular disease.

Quantitative skeletal muscle ultrasonography in children with suspected neuromuscular disease.

We determined prospectively the diagnostic value of quantitative ultrasonography in detecting neuromuscular disorders in children. Ultrasonographic scans of four muscles were made in 36 children with symptoms or signs suggestive of neuromuscular disease, such as muscle weakness and hypotonia. The muscle thickness, ratio of muscle thickness to subcutaneous fat thickness, and echo intensity were determined in each muscle. The echo intensity was measured using computer-assisted gray-scale analysis. Thirteen of the 36 patients had a neuromuscular disorder (6 a myopathy and 7 a neuropathy). Differentiation between neuromuscular diseases and nonneuromuscular diseases could be made on the basis of echo intensities with a sensitivity of 92%, a specificity of 90%, a positive predictive value of 86%, and a negative predictive value of 95%. We conclude that computer-assisted quantitative analysis of muscle echo intensity is a reliable method to discriminate between neuromuscular and nonneuromuscular diseases in children.