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Methods sections are often missing critical details needed to reproduce an experiment. Methodological shortcut citations, in which authors cite previous papers instead of describing the method in detail, may contribute to this problem. This meta-research study used three approaches to systematically examine the use of shortcut citations in neuroscience, biology and psychiatry. First, we examined papers to determine why authors use citations in the methods section and to assess how often shortcut citations were used. Common reasons for using citations in the methods section included explaining how something was done by citing a previous resource that used the method (methodological shortcut citation), giving credit or specifying what was used (who or what citation), and providing context or a justification (why citation). Next, we reviewed 15 papers to determine what can happen when readers follow shortcut citations to find methodological details. While shortcut citations can be used effectively, problems encountered included difficulty identifying or accessing the cited materials, missing or insufficient descriptions of the cited method, and chains of shortcut citations. Third, we examined journal policies. Fewer than one quarter of journals had policies describing how authors should report methods that have been described previously or asking authors to explain modifications of previously described methods. We propose that methodological shortcut citations should meet three criteria; cited resources should describe a method very similar to the authors’ method, provide enough detail to allow others to implement the method, and be open access. We outline actions that authors and journals can take to use shortcut citations responsibly, while fostering a culture of open and reproducible methods reporting.

Early career researchers (ECRs) are important stakeholders leading efforts to catalyze systemic change in research culture and practice. Here, we summarize the outputs from a virtual unconventional conference (unconference), which brought together 54 invited experts from 20 countries with extensive experience in ECR initiatives designed to improve the culture and practice of science. Together, we drafted 2 sets of recommendations for (1) ECRs directly involved in initiatives or activities to change research culture and practice; and (2) stakeholders who wish to support ECRs in these efforts. Importantly, these points apply to ECRs working to promote change on a systemic level, not only those improving aspects of their own work. In both sets of recommendations, we underline the importance of incentivizing and providing time and resources for systems-level science improvement activities, including ECRs in organizational decision-making processes, and working to dismantle structural barriers to participation for marginalized groups. We further highlight obstacles that ECRs face when working to promote reform, as well as proposed solutions and examples of current best practices. The abstract and recommendations for stakeholders are available in Dutch, German, Greek (abstract only), Italian, Japanese, Polish, Portuguese, Spanish, and Serbian. Instituto de Patología Vegetal Fil: Kent, Brianne A. Simon Fraser University. Department of Psychology; Canadá Fil: Holman, Constance. Universitätsmedizin Berlin. BIH QUEST Center for Responsible Research. Berlin Institute of Health at Charité; Alemania Fil: Amoako, Emmanuella. Cape Coast Teaching Hospital. Department of Paediatrics and Child Health; Ghana Fil: Amoako, Emmanuella. University of Cape Coast. School of Medicine. Department of Paediatrics and Child Health; Ghana Fil: Antonietti, Alberto. Politecnico di Milano. Department of Electronics, Information and Bioengineering; Italia Fil: Azam, James M. Stellenbosch University. DSI-NRF Center of Excellence in Epidemiological Modelling and Analysis. Department of Mathematics; Sudáfrica Fil: Ballhausen, Hanne. Universitätsmedizin Berlin. BIH QUEST Center for Responsible Research. Berlin Institute of Health at Charité; Alemania Fil: Fil: Ballhausen, Hanne. Universitätsmedizin Berlin. Department of Paediatric Endocrinology and Diabetes, Charité; Alemania Fil: Bediako, Yaw . University of Ghana. West African Centre for Cell Biology of Infectious Pathogens; Ghana Fil: Belasen, Anat M. Cornell University. Society for Conservation Biology. Department of Ecology and Evolutionary Biology; Estados Unidos Fil: Carneiro, Clarissa F. D. Federal University of Rio de Janeiro. Institute of Medical Biochemistry Leopoldo de Meis; Brasil Fil: Chung Chen, Yen. New York University. Department of Biology; Estados Unidos Fil: Debat, Humberto Julio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; Argentina Fil: Debat, Humberto Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); Argentina Fil: Weissgerber, Tracey L. Universitätsmedizin Berlin. BIH QUEST Center for Responsible Research. Berlin Institute of Health at Charité; Alemania

Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria, and vascular injury in the second half of pregnancy. We hypothesized that endothelium-dependent vascular dysfunction is present in a murine model of preeclampsia based on administration of human preeclamptic sera to interleukin −10−/− mice and studied mechanisms that underlie vascular injury. Pregnant wild type and IL-10−/− mice were injected with either normotensive or severe preeclamptic patient sera (sPE) during gestation. A preeclampsia-like phenotype was confirmed by blood pressure measurements; assessment of albuminuria; measurement of angiogenic factors; demonstration of foot process effacement and endotheliosis in kidney sections; and by accumulation of glycogen in placentas from IL-10−/− mice injected with sPE sera (IL-10−/−sPE). Vasomotor function of isolated aortas was assessed. The IL-10−/−sPE murine model demonstrated significantly augmented aortic contractions to phenylephrine and both impaired endothelium-dependent and, to a lesser extent, endothelium-independent relaxation compared to wild type normotensive mice. Treatment of isolated aortas with indomethacin, a cyclooxygenase inhibitor, improved, but failed to normalize contraction to phenylephrine to that of wild type normotensive mice, suggesting the additional contribution from nitric oxide downregulation and effects of indomethacin-resistant vasoconstricting factors. In contrast, indomethacin normalized relaxation of aortas derived from IL-10−/−sPE mice. Thus, our results identify the role of IL-10 deficiency in dysregulation of the cyclooxygenase pathway and vascular dysfunction in the IL-10−/−sPE murine model of preeclampsia, and point towards a possible contribution of nitric oxide dysregulation. These compounds and related mechanisms may serve both as diagnostic markers and therapeutic targets for preventive and treatment strategies in preeclampsia.

Western blotting is a standard laboratory method used to detect proteins and assess their expression levels. Unfortunately, poor western blot image display practices and a lack of detailed methods reporting can limit a reader’s ability to evaluate or reproduce western blot results. While several groups have studied the prevalence of image manipulation or provided recommendations for improving western blotting, data on the prevalence of common publication practices are scarce. We systematically examined 551 articles published in the top 25% of journals in neurosciences (n = 151) and cell biology (n = 400) that contained western blot images, focusing on practices that may omit important information. Our data show that most published western blots are cropped and blot source data are not made available to readers in the supplement. Publishing blots with visible molecular weight markers is rare, and many blots additionally lack molecular weight labels. Western blot methods sections often lack information on the amount of protein loaded on the gel, blocking steps, and antibody labeling protocol. Important antibody identifiers like company or supplier, catalog number, or RRID were omitted frequently for primary antibodies and regularly for secondary antibodies. We present detailed descriptions and visual examples to help scientists, peer reviewers, and editors to publish more informative western blot figures and methods. Additional resources include a toolbox to help scientists produce more reproducible western blot data, teaching slides in English and Spanish, and an antibody reporting template.

Clinical Science is proud to launch a new translational meta-research collection. Meta-research, or the science of science, applies the scientific method to study science itself. Meta-research is a powerful tool for identifying common problems in scientific papers, assessing their impact, and testing solutions to improve the transparency, rigor, trustworthiness, and usefulness of biomedical research. The collection welcomes science of science studies that link basic science to disease mechanisms, as well as meta-research articles highlighting opportunities to improve transparency, rigor, and reproducibility among the types of papers published in Clinical Science. Submissions might include science of science studies that explore factors linked to successful translation, or meta-research on experimental methods or study designs that are often used in translational research. We hope that this collection will encourage scientists to think critically about current practices and take advantage of opportunities to make their own research more transparent, rigorous, and reproducible.

IntroductionWhile transparent reporting of clinical trials is essential to assess the risk of bias and translate research findings into clinical practice, earlier studies have shown that deficiencies are common. This study examined current clinical trial reporting and transparent research practices in sports medicine and orthopedics.MethodsThe sample included clinical trials published in the top 25% of sports medicine and orthopedics journals over nine months. Two independent reviewers assessed pre-registration, open data and criteria related to scientific rigor, the study sample, and data analysis.ResultsThe sample included 163 clinical trials from 27 journals. While the majority of trials mentioned rigor criteria, essential details were often missing. Sixty percent (confidence interval [CI] 53-68%) of trials reported sample size calculations, but only 32% (CI 25-39%) justified the expected effect size. Few trials indicated the blinding status of all main stakeholders (4%; CI 1-7%). Only 18% (CI 12-24%) included information on randomization type, method, and concealed allocation. Most trials reported participants’ sex/gender (95%; CI 92-98%) and information on inclusion and exclusion criteria (78%; CI 72-84%). Only 20% (CI 14-26%) of trials were pre-registered. No trials deposited data in open repositories.ConclusionsThese results will aid the sports medicine and orthopedics community in developing tailored interventions to improve reporting. While authors typically mention blinding, randomization and other factors, essential details are often missing. Greater acceptance of open science practices, like pre-registration and open data, is needed. These practices have been widely encouraged, we discuss systemic interventions that may improve clinical trial reporting.Registrationhttps://doi.org/10.17605/OSF.IO/9648H

Meta-research, or the science of science, is a powerful technique that scientists can use to improve science, however most scientists are unaware that meta-research exists and courses are rare. This initiative demonstrates the feasibility of a participant-guided “learn by doing” approach, in which a multidisciplinary, global team of early career researchers learned meta-research skills by working together to design, conduct and publish a meta-research study., This Community Page article describes a participant-guided "learn by doing" initiative, in which a multidisciplinary, global team of early career researchers learned meta-research skills by working together to design, conduct and publish a meta-research (science of science) study. Participants can now apply these skills to solve problems in their own fields.

Citations are an important, but often overlooked, part of every scientific paper. They allow the reader to trace the flow of evidence, serving as a gateway to relevant literature. Most scientists are aware of citations’ errors, but few appreciate the prevalence of these problems. The purpose of the present study was to examine how often frequently cited papers in biomedical scientific literature are cited inaccurately. The study included an active participation of the first authors of included papers; to first-hand verify the citations accuracy. Findings from feasibility study, where we reviewed 1540 articles containing 2526 citations of 14 most cited articles in which the authors were affiliated with the Faculty of Medicine University of Belgrade, were further evaluated for external confirmation in an independent verification set of articles. Verification set included 4912 citations identified in 2995 articles that cited 13 most cited articles published by authors affiliated with the Mayo Clinic Division of Nephrology and Hypertension. A citation was defined as being accurate if the cited article supported or was in accordance with the statement by citing authors. At least one inaccurate citation was found in 11 and 15% of articles in the feasibility study and verification set, respectively, suggesting that inaccurate citations are common in biomedical literature. The most common problem was the citation of nonexistent findings (38.4%), followed by an incorrect interpretation of findings (15.4%). One-fifth of inaccurate citations were due to chains of inaccurate citations. Based on these findings, several actions to reduce citation inaccuracies have been proposed.

International audience; The COVID-19 pandemic has thrust preprints into the spotlight, highlighting their advantages and disadvantages. The lack of peer review allows publication to occur with unprecedented speed, but this has raised concerns among biomedical scientists about the quality of the reported research. The study had three primary objectives in regard to COVID-19 preprints: 1. Test the feasibility of automatically and publicly evaluating preprints on a large scale; 2. Assess the prevalence of common quality problems in preprints; and 3. Compare the quality of preprints to published papers. While a substantial fraction (36.2%) of preprints addressed study limitations, the proportion that met other quality criteria was much lower, with only 20% addressing sex as a variable, ~14% sharing open code or data, 7.6% including non-colorblind safe images, and 7.3% showing misleading bar graphs. Both authors and non-authors interacted with the automated Tweets containing reports for preprints. This project shows that it is feasible to conduct large-scale automated screening of preprints for common quality criteria and provide feedback to study authors and readers before publication. These reports can publicly raise awareness about factors that affect study quality and reproducibility, while helping authors to present their research in a more transparent and reproducible manner.

Citations are an important, but often overlooked, part of every scientific paper. They allow the reader to trace the flow of evidence, serving as a gateway to relevant literature. Most scientists are aware of citations errors, but few appreciate the prevalence or consequences of these problems. The purpose of this study was to examine how often frequently cited papers in biomedical scientific literature are cited inaccurately. The study included an active participation of first authors of frequently cited papers; to first-hand verify the citations accuracy. The approach was to determine most cited original articles and their parent authors, that could be able to access, and identify, collect and review all citations of their original work. Findings from feasibility study, where we collected and reviewed 1,540 articles containing 2,526 citations of 14 most cited articles in which the 1st authors were affiliated with the Faculty of Medicine University of Belgrade, were further evaluated for external confirmation in an independent verification set of articles. Verification set included 4,912 citations identified in 2,995 articles that cited 13 most cited articles published by authors affiliated with the Mayo Clinic Division of Nephrology and Hypertension (Rochester, Minnesota, USA), whose research focus is hypertension and peripheral vascular disease. Most cited articles and their citations were determined according to SCOPUS database search. A citation was defined as being accurate if the cited article supported or was in accordance with the statement by citing authors. A multilevel regression model for binary data was used to determine predictors of inaccurate citations. At least one inaccurate citation was found in 11% and 15% of articles in the feasibility study and verification set, respectively, suggesting that inaccurate citations are common in biomedical literature. The main findings were similar in both sets. The most common problem was the citation of nonexistent findings (38.4%), followed by an incorrect interpretation of findings (15.4%). One fifth of inaccurate citations were due to “chains of inaccurate citations,” in which inaccurate citations appeared to have been copied from previous papers. Reviews, longer time elapsed from publication to citation, and multiple citations were associated with higher chance of citation being inaccurate. Based on these findings, several actions that authors, mentors and journals can take to reduce citation inaccuracies and maintain the integrity of the scientific literature have been proposed.

Scientists routinely use images to display data. Readers often examine figures first; therefore, it is important that figures are accessible to a broad audience. Many resources discuss fraudulent image manipulation and technical specifications for image acquisition; however, data on the legibility and interpretability of images are scarce. We systematically examined these factors in non-blot images published in the top 15 journals in 3 fields; plant sciences, cell biology, and physiology (n = 580 papers). Common problems included missing scale bars, misplaced or poorly marked insets, images or labels that were not accessible to colorblind readers, and insufficient explanations of colors, labels, annotations, or the species and tissue or object depicted in the image. Papers that met all good practice criteria examined for all image-based figures were uncommon (physiology 16%, cell biology 12%, plant sciences 2%). We present detailed descriptions and visual examples to help scientists avoid common pitfalls when publishing images. Our recommendations address image magnification, scale information, insets, annotation, and color and may encourage discussion about quality standards for bioimage publishing.

The eLife Early-Career Advisory Group (ECAG), an international group of early-career researchers committed to improving research culture, calls for radical changes at eLife and other journals to address racism in the scientific community and to make science more diverse and inclusive. Fil: Mehta, Devang. University of Alberta; Canadá Fil: Bediako, Yaw. University Of Ghana; Ghana Fil: De Winde, Charlotte M.. Colegio Universitario de Londres; Reino Unido Fil: Ebrahimi, Hedyeh. No especifíca; Fil: Fernández, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Ilangovan, Vinodh. University Aarhus; Dinamarca Fil: Paz Quezada, Carolina. Universidad Bernardo O'higgins; Chile Fil: Riley, Julia L.. Dalhousie University Halifax; Canadá Fil: Saladi, Shyam M.. California Institute of Technology; Estados Unidos Fil: Tay, Andy. No especifíca; Fil: Weissgerber, Tracey. No especifíca

Background Studies have recently examined the role of epigenetic mechanisms in preeclampsia pathophysiology. One commonly examined epigenetic process is DNA methylation. This heritable epigenetic marker is involved in many important cellular functions. The aim of this study was to establish the association between DNA methylation and preeclampsia and to critically appraise the roles of major study characteristics that can significantly impact the association between DNA methylation and preeclampsia. Main body A systematic review was performed by searching PubMed, Web of Science, and EMBASE for original research articles published over time, until May 31, 2019 in English. Eligible studies compared DNA methylation levels in pregnant women with vs. without preeclampsia. Ninety articles were included. Epigenome-wide studies identified hundreds of differentially methylated places/regions in preeclamptic patients. Hypomethylation was the predominant finding in studies analyzing placental tissue (14/19), while hypermethylation was detected in three studies that analyzed maternal white blood cells (3/3). In candidate gene studies, methylation alterations for a number of genes were found to be associated with preeclampsia. A greater number of differentially methylated genes was found when analyzing more severe preeclampsia (70/82), compared to studies analyzing less severe preeclampsia vs. controls (13/27). A high degree of heterogeneity existed among the studies in terms of methodological study characteristics including design (study design, definition of preeclampsia, control group, sample size, confounders), implementation (biological sample, DNA methylation method, purification of DNA extraction, and validation of methylation), analysis (analytical method, batch effect, genotyping, and gene expression), and data presentation (methylation quantification measure, measure of variability, reporting). Based on the results of this review, we provide recommendations for study design and analytical approach for further studies. Conclusions The findings from this review support the role of DNA methylation in the pathophysiology of preeclampsia. Establishing field-wide methodological and analytical standards may increase value and reduce waste, allowing researchers to gain additional insights into the role of DNA methylation in the pathophysiology of preeclampsia.

This protocol describes procedures for non-invasive measurements of sublingual vascular glycocalyx degradation using the GlycoCheck system (RRID:SCR_018254). This includes procedures for setting up the equipment, performing tests, saving data, shutting down the system, troubleshooting and removing dust from the camera lens.

The need to protect public health during the current COVID-19 pandemic has necessitated conference cancellations on an unprecedented scale. As the scientific community adapts to new working conditions, it is important to recognize that some of our actions may disproportionately affect early-career researchers and scientists from countries with limited research funding. We encourage all conference organizers, funders and institutions who are able to do so to consider how they can mitigate the unintended consequences of conference and travel cancellations and we provide seven recommendations for how this could be achieved. The proposed solutions may also offer long-term benefits for those who normally cannot attend conferences, and thus lead to a more equitable future for generations of researchers.

Problems with statistical analyses and the shift toward big data have prompted many researchers to call for improvements in statistics education. A recent study in PLOS Biology assesses changes in the use of data analysis techniques over time to determine which skills young scientists might need.

Renal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We further postulated that podocyte injury and attendant formation of EVs are related mechanistically to cellfree fetal hemoglobin (HbF) in maternal plasma. Our study population included preeclamptic (n=49) and normotensive (n=42) pregnant women recruited at delivery. Plasma measurements included HbF concentrations and concentrations of the endogenous chelators haptoglobin, hemopexin, and α1- microglobulin. We assessed concentrations of urinary EVs containing immunologically detectable podocyte-specific proteins by digital flow cytometry and measured nephrinuria by ELISA. The mechanistic role of HbF in podocyte injury was studied in pregnant rabbits. Compared with urine from women with normotensive pregnancies, urine from women with preeclamptic pregnancies contained a high ratio of podocin-positive to nephrin-positive urinary EVs (podocin+ EVs-to-nephrin+ EVs ratio) and increased nephrinuria, both of which correlated with proteinuria. Plasma levels of hemopexin, which were decreased in women with preeclampsia, negatively correlated with proteinuria, urinary podocin+ EVs-to-nephrin+ EVs ratio, and nephrinuria. Administration of HbF to pregnant rabbits increased the number of urinary EVs of podocyte origin. These findings provide evidence that urinary EVs are reflective of preeclampsia-related altered podocyte protein expression. Furthermore, renal injury in preeclampsia associated with an elevated urinary podocin+ EVs-to-nephrin+ EVs ratio and may be mediated by prolonged exposure to cellfree HbF.

Objectives Pre-eclampsia (PE) is a pregnancy-specific hypertensive disorder that has been associated with cardiovascular risk factors and vascular changes, such as acute atherosis in placental blood vessels, similar to early-stage atherosclerosis. The objective of this study was to determine whether women with PE have increased atherosclerotic burden, as determined by the carotid intima–media thickness (CIMT), compared with women without PE. Methods We conducted a systematic review and meta-analysis of studies that reported CIMT, a non-invasive, ultrasound-based measure of subclinical atherosclerosis, in women who did vs those who did not have PE. Studies were eligible if they had been conducted during pregnancy or during the first decade postpartum, and if CIMT was measured in the common carotid artery. Studies published before 7 March 2016 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Heterogeneity was assessed using the I2 statistic. Standardized mean difference (SMD) was used as a measure of effect size. Results Fourteen studies were included in the meta-analysis. Seven studies were carried out during pregnancy complicated by PE, 10 were carried out up to 10 years postpartum and three included measurements obtained at both time periods. Women who had PE had significantly higher CIMT than did those who did not have PE, both at the time of diagnosis (SMD, 1.10 (95% CI, 0.73–1.48); P < 0.001) and in the first decade postpartum (SMD, 0.58 (95% CI, 0.36–0.79); P < 0.001). Conclusions Atherosclerotic load is present at the time of PE and may be a mechanism associated with the disease. Measurement of CIMT may offer an opportunity for the early identification of premenopausal women with atherosclerotic burden after a PE pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. RESUMEN Objetivos La preeclampsia (PE) es un trastorno hipertensivo especifico del embarazo que ha sido asociada con factores de riesgo cardiovascular y cambios vasculares, tales como aterosis aguda en los vasos sanguineos de la placenta, similares a las primeras etapas de la aterosclerosis. El objetivo de este estudio fue determinar si las mujeres con PE han aumentado la carga aterosclerotica, segun lo determinado por el espesor del complejo intima-media de la arteria carotida (CIMT, por sus siglas en ingles), en comparacion con las mujeres sin PE. Metodos Se realizo una revision sistematica y un metaanalisis de estudios que reportaron el CIMT, una medida no invasiva de la aterosclerosis subclinica obtenida mediante ecografia, comparando mujeres con PE y mujeres sin ella. Solo se incluyeron estudios llevados a cabo durante el embarazo o durante la primera decada despues del parto, y en los que se midio el CIMT en la arteria carotida comun. Se usaron las bases de datos de PubMed, EMBASE y Web of Science para identificar estudios publicados antes del 7 marzo de 2016. Dos revisores utilizaron formularios y protocolos preestablecidos para evaluar de forma independiente la elegibilidad de los estudios, a partir de los titulos y los resumenes, y para realizar un cribado del texto completo, un resumen de los datos y una evaluacion de calidad. La heterogeneidad se evaluo mediante el test estadistico I2. Se uso la diferencia de medias estandarizada (SMD, por sus siglas en ingles) como una medida de la magnitud del efecto. Resultados En el metaanalisis se incluyeron catorce estudios. Siete de los estudios se llevaron a cabo durante embarazos complicados por PE, 10 se realizaron hasta 10 anos despues del parto y tres incluyeron mediciones tomadas en ambos periodos. Las mujeres con PE tuvieron un CIMT significativamente mayor que aquellas que no la tenian, tanto en el momento del diagnostico (SMD 1,10 (I 95%, 0,73-1,48), P

Reports highlighting the problems with the standard practice of using bar graphs to show continuous data have prompted many journals to adopt new visualization policies. These policies encourage authors to avoid bar graphs and use graphics that show the data distribution; however, they provide little guidance on how to effectively display data. We conducted a systematic review of studies published in top peripheral vascular disease journals to determine what types of figures are used, and to assess the prevalence of suboptimal data visualization practices. Among papers with data figures, 47.7% of papers used bar graphs to present continuous data. This primer provides a detailed overview of strategies for addressing this issue by (1) outlining strategies for selecting the correct type of figure depending on the study design, sample size, and the type of variable; (2) examining techniques for making effective dot plots, box plots, and violin plots; and (3) illustrating how to avoid sending mixed messages by aligning the figure structure with the study design and statistical analysis. We also present solutions to other common problems identified in the systematic review. Resources include a list of free tools and templates that authors can use to create more informative figures and an online simulator that illustrates why summary statistics are meaningful only when there are enough data to summarize. Last, we consider steps that investigators can take to improve figures in the scientific literature.

Background Hypertensive disorders of pregnancy (HDP) are associated with increased risks for cardiovascular disease later in life. The HDP incidence is commonly assessed using diagnostic codes, which are not reliable; and typically are expressed per-pregnancy, which may underestimate the number of women with an HDP history after their reproductive years. Objectives This study sought to determine the incidence of HDP expressed as both per-pregnancy and per-woman, and to establish their associations with future chronic conditions and multimorbidity, a measure of accelerated aging, in a population-based cohort study. Methods Using the Rochester Epidemiology Project medical record-linkage system, the authors identified residents of Olmsted County, Minnesota, who delivered between 1976 and 1982. The authors classified pregnancies into normotensive, gestational hypertension, pre-eclampsia, eclampsia, pre-eclampsia superimposed on chronic hypertension, and chronic hypertension using a validated electronic algorithm, and calculated the incidence of HDP both per-pregnancy and per-woman. The risk of chronic conditions between women with versus those without a history of HDP (age and parity 1:2 matched) was quantified using the hazard ratio and corresponding 95% confidence interval estimated from a Cox model. Results Among 9,862 pregnancies, we identified 719 (7.3%) with HDP and 324 (3.3%) with pre-eclampsia. The incidence of HDP and pre-eclampsia doubled when assessed on a per-woman basis: 15.3% (281 of 1,839) and 7.5% (138 of 1,839), respectively. Women with a history of HDP were at increased risk for subsequent diagnoses of stroke (hazard ratio [HR]: 2.27; 95% confidence interval [CI]: 1.37 to 3.76), coronary artery disease (HR: 1.89; 95% CI: 1.26 to 2.82), cardiac arrhythmias (HR: 1.62; 95% CI: 1.28 to 2.05), chronic kidney disease (HR: 2.41; 95% CI: 1.54 to 3.78), and multimorbidity (HR: 1.25; 95% CI: 1.15 to 1.35). Conclusions The HDP population-based incidence expressed per-pregnancy underestimates the number of women affected by this condition during their reproductive years. A history of HDP confers significant increase in risks for future chronic conditions and multimorbidity.

Background Preeclampsia is a pregnancy-specific hypertensive disorder characterized by impaired angiogenesis. We postulate that senescence of mesenchymal stem cells (MSC), multipotent cells with pro-angiogenic activities, is one of the mechanisms by which systemic inflammation exerts inhibitory effects on angiogenesis in preeclampsia. Methods MSC were isolated from abdominal fat tissue explants removed during medically indicated C-sections from women with preeclampsia (PE-MSC, n = 10) and those with normotensive pregnancies (NP-MSC, n = 12). Sections of the frozen subcutaneous adipose tissue were assessed for inflammation by staining for tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1. Viability, proliferation, and migration were compared between PE-MSC vs. NP-MSC. Apoptosis and angiogenesis were assayed before and after treatment with a senolytic agent (1 μM dasatinib) using the IncuCyte S3 Live-Cell Analysis System. Similarly, staining for senescence-associated beta galactosidase (SABG) and qPCR for gene expression of senescence markers, p16 and p21, as well as senescence-associated secretory phenotype (SASP) components, IL-6, IL-8, MCP-1, and PAI-1, were studied before and after treatment with dasatinib and compared between PE and NP. Results After in vitro exposure to TNF-alpha, MSC demonstrated upregulation of SASP components, including interleukins-6 and -8 and MCP-1. Staining of the subcutaneous adipose tissue sections revealed a greater inflammatory response in preeclampsia, based on the higher levels of both TNF-alpha and MCP-1 compared to normotensive pregnancies (p p = 0.012), lower proliferation (p = 0.005), and higher migration (p = 0.023). At baseline, PE-MSC demonstrated a senescent phenotype, reflected by more abundant staining for SABG (p p p Conclusions Our data suggest that MSC senescence exerts inhibitory effects on angiogenesis in preeclampsia. Senolytic agents may offer the opportunity for mechanism-based therapies.

Background The endothelial glycocalyx is a vasoprotective barrier between the blood and endothelium. We hypothesized that glycocalyx degradation is present in preeclampsia, a pregnancy‐specific hypertensive disorder characterized by endothelial dysfunction and activation. Methods and Results We examined the sublingual glycocalyx noninvasively using sidestream dark field imaging in the third trimester among women with normotensive pregnancies (n=73), early (n=14) or late (n=29) onset preeclampsia, or gestational diabetes mellitus (n=21). We calculated the width of the glycocalyx that was permeable to red blood cells (called the perfused boundary region , a measure of glycocalyx degradation) and the percentage of vessels that were filled with red blood cells ≥50% of the time (a measure of microvascular perfusion). In addition, we measured circulating levels of glycocalyx components, including heparan sulfate proteoglycans, hyaluronic acid, and SDC1 (syndecan 1), in a subset of participants by ELISA . Repeated‐measures ANOVA was performed to adjust for vessel diameter and caffeine intake. Women with early onset preeclampsia showed higher glycocalyx degradation, indicated by a larger perfused boundary region (mean: 2.14 [95% CI, 2.05–2.20]), than the remaining groups (mean: normotensive: 1.99 [95% CI, 1.95–2.02], P =0.002; late‐onset preeclampsia: 2.01 [95% CI, 1.96–2.07], P =0.024; gestational diabetes mellitus: 1.97 [95% CI, 1.91–2.04], P =0.004). The percentage of vessels that were filled with red blood cells was significantly lower in early onset preeclampsia. These structural glycocalyx changes were accompanied by elevated plasma concentrations of the glycocalyx components, heparan sulfate proteoglycans and hyaluronic acid, in early onset preeclampsia compared with normotensive pregnancy. Conclusions Glycocalyx degradation and reduced microvascular perfusion are associated with endothelial dysfunction and activation and vascular injury in early onset preeclampsia.

Transparent reporting is essential for the critical evaluation of studies. However, the reporting of statistical methods for studies in the biomedical sciences is often limited. This systematic review examines the quality of reporting for two statistical tests, t-tests and ANOVA, for papers published in a selection of physiology journals in June 2017. Of the 328 original research articles examined, 277 (84.5%) included an ANOVA or t-test or both. However, papers in our sample were routinely missing essential information about both types of tests: 213 papers (95% of the papers that used ANOVA) did not contain the information needed to determine what type of ANOVA was performed, and 26.7% of papers did not specify what post-hoc test was performed. Most papers also omitted the information needed to verify ANOVA results. Essential information about t-tests was also missing in many papers. We conclude by discussing measures that could be taken to improve the quality of reporting.

Endothelial dysfunction is believed to play a critical role in preeclampsia; however, it is unclear whether this dysfunction precedes the pregnancy or is caused by pathophysiological events in early pregnancy. It is also unclear for how long vascular dysfunction may persist postpartum and whether it represents a mechanism linking preeclampsia with future cardiovascular disease. Our objective was to determine whether women with preeclampsia had worse vascular function compared with women who did not have preeclampsia by performing a systematic review and meta-analysis of studies that examined endothelial dysfunction using flow-mediated dilation. We included studies published before May 29, 2015, that examined flow-mediated dilation before, during, or after preeclampsia. Differences in flow-mediated dilation between study groups were evaluated by standardized mean differences. Out of 610 abstracts identified through PubMED, EMBASE, and Web of Science, 37 studies were eligible for the meta-analysis. When compared with women who did not have preeclampsia, women who had preeclampsia had lower flow-mediated dilation before the development of preeclampsia (≈20–29 weeks gestation), at the time of preeclampsia, and for 3 years postpartum, with the estimated magnitude of the effect ranging between 0.5 and 3 standard deviations. Similar effects were observed when the analysis was limited to studies that excluded women with chronic hypertension, smokers, or both. Vascular dysfunction predates preeclampsia and may contribute to its pathogenesis. Future studies should address whether vascular changes that persist after preeclamptic pregnancies may represent a mechanistic link with increased risk for future cardiovascular disease.

Background Atrial fibrillation/flutter ( AF ) produces significant morbidity in women and is typically attributed to cardiac remodeling from multiple causes, particularly hypertension. Hypertensive pregnancy disorders ( HPD s) are associated with future hypertension and adverse cardiac remodeling. We evaluated whether women with AF were more likely to have experienced a HPD compared with those without. Methods and Results A nested case–control study was conducted within a cohort of 7566 women who had a live or stillbirth delivery in Olmsted County, Minnesota between 1976 and 1982. AF cases were matched (1:1) to controls based on date of birth, age at first pregnancy, and parity. AF and pregnancy history were confirmed by chart review. We identified 105 AF cases: mean age 57±8 (mean± SD ) years, (controls 56±8 years), 32±8 years (controls 31±8 years) after the first pregnancy. Cases were more likely to have obesity during childbearing years, and hypertension, diabetes mellitus, dyslipidemia, coronary disease, valvular disease, and heart failure at the time of AF diagnosis. Cases were more likely to have a history of HPD s, compared with controls: 28/105 (26.7%) cases versus 12/105 (11.4%) controls, odds ratio: 2.60 (95% confidence interval, 1.21–6.04). After adjustment for hypertension and obesity, the association was attenuated and no longer statistically significant; odds ratio (95% confidence interval, 2.12 (0.92–5.23). Conclusions Women with AF are more likely to have had a HPD , a relationship at least partially mediated by associated obesity and hypertension. Given the high morbidity of AF , studies evaluating the benefit of screening for and management of cardiovascular risk factors in women with a history of HPD should be performed.

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 concentrations5.5 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.

Objectives To develop and validate criteria for the retrospective diagnoses of hypertensive disorders of pregnancy that would be amenable to the development of an electronic algorithm, and to compare the accuracy of diagnoses based on both the algorithm and diagnostic codes with the gold standard, of physician-made diagnoses based on a detailed review of medical records using accepted clinical criteria. Patients and Methods An algorithm for hypertensive disorders of pregnancy was developed by first defining a set of criteria for retrospective diagnoses, which included relevant clinical variables and diagnosis of hypertension that required blood pressure elevations in greater than 50% of readings ("the 50% rule"). The algorithm was validated using the Rochester Epidemiology Project (Rochester, Minnesota). A stratified random sample of pregnancies and deliveries between January 1, 1976, and December 31, 1982, with the algorithm-based diagnoses was generated for review and physician-made diagnoses (normotensive, gestational hypertension, and preeclampsia), which served as the gold standard; the targeted cohort size for analysis was 25 per diagnosis category according to the gold standard. Agreements between (1) algorithm-based diagnoses and (2) diagnostic codes and the gold standard were analyzed. Results Sensitivities of the algorithm for 25 normotensive pregnancies, 25 with gestational hypertension, and 25 with preeclampsia were 100%, 88%, and 100%, respectively, and specificities were 94%, 100%, and 100%, respectively. Diagnostic code sensitivities were 96% for normotensive pregnancies, 32% for gestational hypertension, and 96% for preeclampsia, and specificities were 78%, 96%, and 88%, respectively. Conclusion The electronic diagnostic algorithm was highly sensitive and specific in identifying and classifying hypertensive disorders of pregnancy and was superior to diagnostic codes.

Pre-eclampsia is a pregnancy-specific hypertensive disorder that may lead to serious maternal and fetal complications. It is a multisystem disease that is commonly, but not always, accompanied by proteinuria. Its cause(s) remain unknown, and delivery remains the only definitive treatment. It is increasingly recognized that many pathophysiological processes contribute to this syndrome, with different signaling pathways converging at the point of systemic endothelial dysfunction, hypertension, and proteinuria. Different animal models of pre-eclampsia have proven utility for specific aspects of pre-eclampsia research, and offer insights into pathophysiology and treatment possibilities. Therapeutic interventions that specifically target these pathways may optimize pre-eclampsia management and may improve fetal and maternal outcomes. In addition, recent findings regarding placental, endothelial, and podocyte pathophysiology in pre-eclampsia provide unique and exciting possibilities for improved diagnostic accuracy. Emerging evidence suggests that testing for urinary podocytes or their markers may facilitate the prediction and diagnosis of pre-eclampsia. In this review, we explore recent research regarding placental, endothelial, and podocyte pathophysiology. We further discuss new signaling and genetic pathways that may contribute to pre-eclampsia pathophysiology, emerging screening and diagnostic strategies, and potential targeted interventions.

Free vascular endothelial growth factor (VEGF) is undetectable in plasma during human pregnancy. However, studies examining pregnant rats have reported both low (8–29 pg/ml) and high (527–1,030 pg/ml) free VEGF. These discrepancies cast uncertainty over the use of rat models to study angiogenic factors in pregnancy and preeclampsia. This study investigates methodological factors that may explain these discrepancies. Plasma VEGF in nonpregnant, day 7 pregnant, and day 19 pregnant rats was measured using rat and mouse ELISAs (R&D Systems). The rat ELISA detected VEGF in plasma from nonpregnant rats but not in plasma from day 19 pregnant rats. The mouse ELISA detected higher VEGF concentrations than the rat ELISA in every sample tested. This discrepancy was greater in day 19 pregnant rats (median: 2,273 vs. 0 pg/ml) than in nonpregnant (97 vs. 20 pg/ml) and day 7 pregnant (66 vs. 2 pg/ml) rats. Recovery of recombinant rat VEGF (rrVEGF) spiked into plasma from nonpregnant and day 7 pregnant rats was high for the rat ELISA (82–105%) but low for the mouse ELISA (17–22%). The rat ELISA did not recover rrVEGF in plasma from day 19 pregnant rats, suggesting that this ELISA measures free VEGF. The use of the rat versus mouse ELISA likely explains the differences in reported VEGF concentrations in pregnant rats. While the rat ELISA appears to measure free VEGF, plasma concentrations in nonpregnant and pregnant rats are below the assay sensitivity limit. As most previous studies of pregnant rats used the mouse VEGF ELISA, these data should be interpreted cautiously.

The anti-oxidant and proangiogenic protein haptoglobin (Hp) is believed to be important for implantation and pregnancy, although its specific role is not known. The three phenotypes (1-1, 2-1 and 2-2) differ in structure and function. Hp 2-2 is associated with increased vascular stiffness in other populations. We examined whether Hp phenotype is associated with abnormal uterine artery Doppler (UAD) in pregnancy.We conducted a secondary analysis of a preeclampsia prediction cohort nested within a larger placebo-controlled randomized clinical trial of antioxidants for prevention of preeclampsia. We determined Hp phenotype in 2184 women who completed UAD assessments at 17 weeks gestation. Women with notching were re-evaluated for persistent notching at 24 weeks' gestation. Logistic regression was used to assess differences in UAD indices between phenotype groups.Hp phenotype did not significantly influence the odds of having any notch (p = 0.32), bilateral notches (p = 0.72), or a resistance index (p = 0.28) or pulsatility index (p = 0.67) above the 90th percentile at 17 weeks' gestation. Hp phenotype also did not influence the odds of persistent notching at 24 weeks (p = 0.25).Hp phenotype is not associated with abnormal UAD at 17 weeks' gestation or with persistent notching at 24 weeks.

Objective To measure carotid artery intima-media thickness (CIMT), a marker of subclinical atherosclerosis, in postmenopausal women with and without histories of preeclampsia and to synthesize these results with those from prior studies of CIMT performed 10 or more years after preeclamptic pregnancies. Patients and Methods Forty women (median age, 59 years) with histories of preeclampsia and 40 with histories of normotensive pregnancy (confirmed by medical record review) were selected from women who resided and gave birth in Olmsted County, Minnesota, between January 1, 1976, and December 31, 1982. The participants were identified and recruited in 2014-2015, and CIMT was measured by B-mode ultrasonography. Meta-analysis included CIMT studies that were performed 10 or more years after preeclamptic pregnancies and which were identified through PubMed, EMBASE, and Web of Science. Heterogeneity was assessed using the I 2 statistic. Standardized mean difference was used as a measure of effect size. Results Carotid artery intima-media thickness, expressed as a median (interquartile range), was greater in the preeclamptic than in the normotensive group (0.80 mm [0.75-0.85 mm] vs 0.73 mm [0.70-0.78]; P =.004); the odds of having CIMT higher than threshold (0.77 mm) was statistically significant after adjusting for confounding factors (odds ratio, 3.17; 95% CI, 1.10-9.14). A meta-analysis of 10 studies conducted 10 or more years post partum included 813 women with and 2874 without histories of preeclampsia. Carotid artery intima-media thickness was greater among women with histories of preeclampsia, with a standardized mean difference of 0.18 and 95% CI of 0.05 to 0.30 mm ( P =.004). Conclusion Among women with histories of preeclampsia, CIMT may identify those with subclinical atherosclerosis, thus offering an opportunity for early intervention.

Data presentation for scientific publications in small sample size studies has not changed substantially in decades. It relies on static figures and tables that may not provide sufficient information for critical evaluation, particularly of the results from small sample size studies. Interactive graphics have the potential to transform scientific publications from static reports of experiments into interactive datasets. We designed an interactive line graph that demonstrates how dynamic alternatives to static graphics for small sample size studies allow for additional exploration of empirical datasets. This simple, free, web-based tool (http://statistika.mfub.bg.ac.rs/interactive-graph/) demonstrates the overall concept and may promote widespread use of interactive graphics., This article examines the potential for interactive graphics to transform scientific papers from static publications into interactive datasets and provides a web-based tool for creating interactive line graphs.

Several registry-based studies, using diagnostic codes, have suggested that preeclampsia is a risk factor for end-stage renal disease (ESRD). However, because the 2 diseases share risk factors, the true nature of their association remains uncertain. Our goals were to conduct a population-based study to determine the magnitude of the association between preeclampsia and ESRD and evaluate the role of shared risk factors.Population-based nested case-control study.The US Renal Data System was used to identify women with ESRD from a cohort of 34,581 women who gave birth in 1976 to 2010 in Olmsted County, MN. 44 cases of ESRD were identified and each one was matched to 2 controls based on year of birth (±1 year), age at first pregnancy (±2 years), and parity (±1 or ≥4).Preeclamptic pregnancy, confirmed by medical record review.ESRD.Prepregnancy serum creatinine and urine protein measurements were recorded. Comorbid conditions existing prior to pregnancy were abstracted from medical records and included kidney disease, obesity, diabetes, and hypertension.There was evidence of kidney disease prior to the first pregnancy in 9 of 44 (21%) cases and 1 of 88 (1%) controls. Per chart review, 8 of 44 (18%) cases versus 4 of 88 (5%) controls had preeclamptic pregnancies (unadjusted OR, 4.0; 95% CI, 1.21-13.28). Results were similar after independent adjustment for race, education, diabetes, and hypertension prior to pregnancy. However, the association was attenuated and no longer significant after adjustment for obesity (OR, 3.25; 95% CI, 0.93-11.37).The limited number of ESRD cases and missing data for prepregnancy kidney function.Our findings confirm that there is a sizable association between preeclampsia and ESRD; however, obesity is a previously unexplored confounder. Pre-existing kidney disease was common, but not consistently coded or diagnosed.

Background— Hypertensive pregnancy disorders have been associated with subjective cognitive complaints or brain white-matter lesions 5 to 10 years after the hypertensive pregnancy. The long-term effects of hypertensive pregnancies on brain structure and cognitive function remain unknown. Methods and Results— This study included 1279 women who participated in the Family Blood Pressure Project Genetic Epidemiology Network of Arteriopathy (GENOA) study. As part of the ancillary Genetics of Microangiopathic Brain Injury (GMBI) study, a neurocognitive battery was administered; 1075 also had a brain magnetic resonance imaging. A history of a hypertensive pregnancy disorder was obtained by a self-report using a validated questionnaire. Linear models fit with generalized estimating equations were used to assess the association between hypertensive pregnancy disorders and cognition, adjusting for age, race, education, body mass index, smoking, current hypertension, hypertension duration, and family history of hypertension. Regression models for the brain magnetic resonance imaging outcomes also were adjusted for total intracranial volume. Women with histories of hypertensive pregnancy disorders performed worse on all measures of processing speed (Digital Symbol Substitution Test [mean score, 41.2 versus 43.4; P =0.005], Trail Making Test Part A [mean seconds, 45.1 versus 42.2; P =0.035], and Stroop [mean score, 173.9 versus 181.0; P =0.002]) and had smaller brain volumes compared with women with histories of normotensive pregnancies (286 versus 297; P =0.023). Conclusions— Hypertensive pregnancy disorders are associated with worse performance on tests of processing speed and smaller brain volumes decades later. Population-based studies are needed to provide critical insight as to the contribution of hypertensive pregnancies to risk of cognitive decline and dementia.

Whether brachial artery FMD (flow-mediated dilation) is altered in pregnancy by 28–35 weeks compared with non-pregnant women remains controversial. The controversy may be due to limitations of previous studies that include failing to: (i) test non-pregnant controls in the mid-late luteal phase, (ii) account for effects of pregnancy on the dilatory shear stimulus, (iii) account for physical activity or (iv) control for inter-individual variation in the time to peak FMD. In the present study, brachial artery FMD was measured in 17 active and eight sedentary pregnant women (34.1±1.6 weeks of gestation), and in 19 active and 11 sedentary non-pregnant women (mid-late luteal phase). Decreased vascular tone secondary to increased shear stress contributes minimally to pregnancy-induced increases in baseline brachial artery diameter, as shear stress removal during distal cuff inflation in pregnant women did not reduce diameter to baseline levels observed in non-pregnant controls. Neither the shear stimulus nor the percentage FMD was affected by pregnancy or regular exercise. Continuous diameter measurements are required to control for delayed peak dilation during pregnancy (57±15 compared with 46±15 s; P=0.012), as post-release diameter measured at 60 or 55–65 s post-release underestimated FMD to a greater extent in non-pregnant than in pregnant women.

Radial artery diameter decreases when a wrist cuff is inflated to stop blood flow to distal tissue. This phenomenon, referred to as low flow-mediated vasoconstriction (L-FMC), was proposed as a vascular function test. Recommendations that L-FMC be measured concurrently with flow-mediated dilation (FMD) were based on radial artery data. However, cardiovascular disease prediction studies traditionally measure brachial artery FMD. Therefore, studies should determine whether L-FMC occurs in the brachial artery. The hypothesis that reduced shear causes L-FMC has not been tested. Brachial and radial artery L-FMC and FMD were assessed in active nonpregnant ( n = 17), inactive nonpregnant ( n = 10), active pregnant ( n = 15, 34.1 ± 1.2 wk gestation), and inactive pregnant ( n = 8, 34.2 ± 2.2 wk gestation) women. Radial artery diameter decreased significantly during occlusion in all groups (nonpregnant, −4.4 ± 4.2%; pregnant, −6.4 ± 3.2%). Brachial artery diameter did not change in active and inactive nonpregnant, and inactive pregnant women; however, the small decrease in active pregnant women was significant. Occlusion decreased shear rate in both arteries, yet L-FMC only occurred in the radial artery. Radial artery L-FMC was not correlated with the reduction in shear rate. L-FMC occurs in the radial but not the brachial artery and is not related to changes in shear rate. Positive correlations between L-FMC (negative values) and FMD (positive values) suggest that radial artery FMD may be reduced among women who experience greater L-FMC. Studies should clarify the underlying stimulus and mechanisms regulating L-FMC, and test the hypothesis that endothelial dysfunction is manifested as enhanced brachial artery L-FMC, but attenuated radial artery L-FMC.

Hypertension in pregnancy is a risk factor for future hypertension and cardiovascular disease. This may reflect an underlying familial predisposition or persistent damage caused by the hypertensive pregnancy. We sought to isolate the effect of hypertension in pregnancy by comparing the risk of hypertension and cardiovascular disease in women who had hypertension in pregnancy and their sisters who did not using the dataset from the Genetic Epidemiology Network of Arteriopathy study, which examined the genetics of hypertension in white, black, and Hispanic siblings. This analysis included all sibships with at least one parous woman and at least one other sibling. After gathering demographic and pregnancy data, BP and serum analytes were measured. Disease-free survival was examined using Kaplan-Meier curves and Cox proportional hazards regression. Compared with their sisters who did not have hypertension in pregnancy, women who had hypertension in pregnancy were more likely to develop new onset hypertension later in life, after adjusting for body mass index and diabetes (hazard ratio 1.75, 95% confidence interval 1.27-2.42). A sibling history of hypertension in pregnancy was also associated with an increased risk of hypertension in brothers and unaffected sisters, whereas an increased risk of cardiovascular events was observed in brothers only. These results suggest familial factors contribute to the increased risk of future hypertension in women who had hypertension in pregnancy. Further studies are needed to clarify the potential role of nonfamilial factors. Furthermore, a sibling history of hypertension in pregnancy may be a novel familial risk factor for future hypertension.