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ObjectivesThis study investigated whether an individual's risk of developing lone atrial fibrillation (AF) before age 60 years is associated with lone AF in relatives.BackgroundGenetic factors may play a role in the development of lone AF.MethodsUsing Danish national registers, a cohort was established of ∼4 million persons born between 1950 and 2008, and those with a family history of lone AF (AF without preceding cardiovascular/endocrine diagnoses) were identified. Individuals were followed up until the first diagnosis of lone AF. Poisson regression was used to estimate incidence rate ratios (IRRs).ResultsIn ∼92 million person-years of follow-up, 9,507 persons were identified as having lone AF. The IRRs for lone AF given an affected first- or second-degree relative were 3.48 (95% confidence interval [CI]: 3.08 to 3.93) and 1.64 (95% CI: 1.04 to 2.59), respectively. IRRs were higher for men than for women but were not associated with the affected relative's sex. IRR for lone AF was 6.24 (95% CI: 2.59 to 15.0), given at least 2 first-degree relatives affected with lone AF. The IRR for lone AF in persons aged

ObjectivesThe purpose of this study was to examine the effect of a family history of premature death, cardiovascular death in particular, on the risk of early cardiovascular disease.BackgroundStudies suggest that fatal cardiovascular events and less severe cardiovascular diseases may co-occur in families. Consequently, a family history of premature death may indicate a familial cardiac frailty that predisposes to early cardiovascular disease.MethodsWe ascertained family history of premature death (age

Increasing demands for accountability in educational programming have resulted in increasing calls for program evaluation in educational organizations. Many organizations include conducting program evaluations as part of the job responsibilities of program staff. Cooperative Extension is a complex organization offering non-formal educational programs through land grant universities. Many Extension services require non-formal educational program evaluations be conducted by field-based Extension educators. Evaluation research has focused primarily on the efforts of professional, external evaluators. The work of program staff with many responsibilities including program evaluation has received little attention. This study examined how field based Extension educators (i.e. program staff) in four Extension services use the results of evaluations of programs that they have conducted themselves. Four types of evaluation use are measured and explored; instrumental use, conceptual use, persuasive use and process use. Results indicate that there are few programmatic changes as a result of evaluation findings among the non-formal educators surveyed in this study. Extension educators tend to use evaluation results to persuade others about the value of their programs and learn from the evaluation process. Evaluation use is driven by accountability measures with very little program improvement use as measured in this study. Practical implications include delineating accountability and program improvement tasks within complex organizations in order to align evaluation efforts and to improve the results of both. There is some evidence that evaluation capacity building efforts may be increasing instrumental use by educators evaluating their own programs.

Introduction By definition, elevated blood pressure is central to preeclampsia (PE) diagnostics. However, blood pressure varies with many factors, including physical activity, hydration, and stress. Degree of proteinuria, another finding diagnostic of PE, may also fluctuate due to dipstick test inaccuracy, hydration level, and specimen collection technique. Thus, a PE diagnosis made according to current criteria does not always accurately represent the final clinical picture. Objectives To compare the clinical profiles of 1) women who receive a PE diagnosis but later cease to fulfill the diagnostic criteria for PE, 2) women who cycle between diagnostic groups, and 3) women who consistently fulfill the diagnostic criteria for PE. Patients and methods The PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) study is an ongoing longitudinal prospective study being conducted at two hospitals in Copenhagen. Approximately 300 women presenting to the obstetrics departments of these hospitals with signs or symptoms of PE have already been recruited and followed to the end of pregnancy with serial blood tests and repeated cardiac function measurements obtained using the USCOM-1A device. We compare clinical variables (e.g. blood pressure at multiple time points, dipstick proteinuria, symptoms, pre-pregnancy body mass index, age) and USCOM-derived cardiac function measurements (stroke volume, cardiac output, systemic vascular resistance and their indexed values) across groups of women with varying clinical courses. Results and conclusion We present clinical and hemodynamic profiles for PEACH women who can consistently be classified as having PE and those who cannot. It is not unusual for a woman who initially meets the criteria for PE to later stabilize and be re-classified with gestational hypertension or no hypertensive disorder at all; others continue to have blood pressure fluctuations around the levels considered diagnostic for PE. Women who initially present with hypertension and proteinuria but later appear to become non-preeclamptic are an interesting group of patients whose management presents a challenge. A new diagnostic paradigm is urgently needed; however, until PE diagnosis is revolutionized, it may be beneficial to add a temporal component to the current criteria.

Introduction Preeclampsia has been linked with later cognitive impairment and brain atrophy, but epidemiologic studies have not confirmed a link with dementia later in life. Objective To explore associations between preeclampsia and later dementia, by dementia subtype and timing of onset. Methods Our study cohort included all women in Denmark with ⩾1 live birth or stillbirth between 1978 and 2015. Using Danish national registers, we identified women who subsequently developed dementia. We used Cox regression to estimate hazard ratios comparing dementia risk among women with and without a history of preeclampsia. Results Our cohort consisted of 1,178,005 women with 20,352,695 person-years of follow-up. Women with a history of preeclampsia had a 53% increase in risk of dementia overall (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.26–1.85) and more than three times the risk of vascular dementia (HR, 3.46; 95% CI, 1.97–6.10) later in life, compared with women with no history of preeclampsia. In contrast, only modest associations were observed for both Alzheimer’s disease (HR 1.45; 95% CI 1.05–1.99) and unspecified dementia (HR, 1.40; 95% CI 1.08–1.83). The association with vascular dementia appeared to be stronger for late-onset disease (age ⩾65 years, HR, 6.53; 95% CI, 2.82–15.1) than for early-onset disease (age Discussion Preeclampsia was associated with an increased risk of dementia, vascular dementia in particular. Cardiovascular disease, hypertension, and diabetes were unlikely to mediate the associations substantially, suggesting that preeclampsia and vascular dementia may share underlying mechanisms or susceptibility pathways.

Background Preeclampsia (PE), a pregnancy disorder often characterized by renal complications, has previously been associated with later end-stage renal disease. We conducted a nationwide register-based cohort study to explore associations between PE and later kidney disease. Methods Using Danish health registers, we identified all women with pregnancies lasting ⩾20 weeks in Denmark, 1978–2015. PE included preeclampsia, eclampsia or HELLP syndrome registered from 30 days before delivery to 7 days postpartum and was classified as early preterm, late preterm or term based on timing of delivery ( Results The study cohort consisted of 1,072,330 women followed for 19,994,470 person-years (average: 18.6 years/woman). During follow-up, 6060 women developed acute kidney disease and 3082 developed chronic kidney disease. Compared with women without PE delivering in the same gestational age interval, women with a history of PE had only modestly increased rates of acute kidney disease, but significantly higher rates of post-pregnancy chronic kidney disease: early preterm PE, HR 3.93, 95% confidence interval [CI] 2.90–5.33; late preterm PE, HR 2.81, 95% CI 2.13–3.71; term PE, HR 2.27, 95% CI 2.02–2.55. Associations for glomerular disease were especially striking (e.g. early preterm PE, HR 5.27, 95% CI 3.32–8.35). Conclusion Our study provides the first population-based evidence that PE, early PE in particular, is associated with several types of kidney disease later in life.

Introduction Women with a history of preeclampsia (PE) have an increased risk of cardiovascular disease (CVD) later in life. To assess whether PE and CVD might share underlying, potentially heritable mechanisms, we examined the familial co-aggregation of PE and CVD. Objectives To determine whether PE in daughters is associated with CVD in parents, by timing of PE onset in the daughters and type of CVD in the parents. Material and methods Using Danish health and civil registers, we identified all women with pregnancies in 1978–2015, along with their parents (656,027 mothers and 581,035 fathers). We followed the parents from the first pregnancy in a daughter until registration of an ischemic event (myocardial infarction [MI], cerebrovascular infarction or ischemic heart disease), death, immigration or the end of follow-up (31 December 2015). Using Cox regression, we estimated hazard ratios (HRs) for ischemic events in parents by history of PE in daughters. Results Parents with one daughter with a history of PE had 1.15 (95% confidence interval [CI] 1.13–1.18) times the rate of ischemic events as parents whose daughters had no history of PE. Having two or more daughters with a history of PE yielded an HR of 1.28 (95% CI 1.13–1.45). The corresponding HRs for MI alone were 1.21 (95% CI 1.17–1.25, 1 daughter with PE) and 1.55 (95% CI 1.29–1.86, ⩾ 2 daughters with PE). Effect magnitudes did not differ for mothers and fathers. Early-onset (delivery Conclusion PE in daughters is associated with an increased risk of ischemic events, MI in particular, in parents. Increasing strength of association with increasing number of affected daughters, similar effect magnitudes for mothers and fathers, and stronger associations with early-onset PE than with term PE, all suggest that the association between PE and CVD can be explained by common heritable mechanisms, rather than shared behavioral risk factors.

Introduction The preeclampsia (PE) syndrome almost certainly encompasses multiple disease entities. Cardiovascular dysfunction is well documented in early-onset (GA Objectives To compare repeated cardiac function measurements (stroke volume, cardiac output, and total vascular resistance) measured in normotensive pregnancies and pregnancies complicated with late-onset PE. Patients and methods The PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) study is an ongoing longitudinal prospective study being conducted at two university hospitals in Copenhagen, Denmark. PEACH recruits women presenting to the obstetrics departments of these hospitals with signs of hypertensive disorders of pregnancy (HDP) and follows them until the end of pregnancy with serial blood tests and repeated cardiac function measurements obtained using the USCOM-1A device. The study also follows normotensive pregnant women frequency matched to the women in the HDP group and assesses their cardiac function in gestational weeks 28, 35, 38 and 40. USCOM data on cardiac function are analyzed using linear mixed models that include a random personal effect (woman-specific effect), a time-dependent gestational age effect (a trend describing how normal cardiac function changes over the course of pregnancy) and a time-dependent PE effect (how PE – overall or by subtypes – affects cardiac function at a given point during pregnancy). Results and conclusion We compare cardiac function measurements and corresponding indexed values from the first 100 women recruited to the PEACH study with late-onset PE and 100 appropriate controls, at given points during pregnancy, adjusting for age, parity, hospital, ethnicity and other potential confounders. The resulting profiles should help to clarify what role cardiac function monitoring can play in prediction, triage, diagnosis and/or management of late-onset PE.

Introduction Women with preeclampsia often have higher levels of anti-angiogenic factors than women with normotensive pregnancies. Since angiogenesis is necessary for solid cancer growth and spread, women with a history of preeclampsia may have a reduced risk of solid cancers. Objectives To investigate the association between hypertensive disorders of pregnancy (HDP: preeclampsia and gestational hypertension) and later risks of solid and non-solid cancers. Methods We applied Cox regression to Danish health register data and estimated hazard ratios (HRs) for solid and non-solid cancers, comparing women with and without a history of HDP. Results In a cohort of 1.08 million women with ⩾ 1 birth in 1978–2011, 68,236 women had ⩾ 1 pregnancy complicated by HDP; during follow-up, 42,236 and 1,899 women developed solid and non-solid cancers, respectively. A history of HDP was not associated with the rate of solid cancer (HR 0.96, 95% confidence interval [CI] 0.92–1.00), regardless of HDP severity, nor was it associated with delayed solid cancer onset. Interestingly, prior HDP were modestly associated with the rate of non-solid cancer (HR 1.21, 95% CI 1.02–1.45). In analyses of specific cancer subtypes, prior HDP were associated with reduced rates of breast (HR 0.89, 95% CI 0.83–0.95) and lung cancer (HR 0.66, 95% CI 0.54–0.79) and increased rates of leukemia (HR 1.43, 95% CI 1.12–1.83), endometrial (HR 1.62, 95% CI 1.33–1.97) and urinary tract cancer (HR 1.42, 95% CI 1.09–1.97). Conclusion Prior HDP were not associated with overall solid cancer risk, suggesting that observed associations with specific cancer subtypes are probably not explained by an angiogenic imbalance.

Introduction Pregnant women carrying fetuses with heart defects and women with hypertensive disorders of pregnancy (HDP) both often exhibit angiogenic imbalances, suggesting that the same underlying processes may play a role in the etiology of heart defects and the pathology associated with HDP. Objectives To determine whether fetal heart defects are associated with an increased risk of maternal HDP, and whether the mechanisms driving the association are primarily maternal or fetal. Methods Using Danish national registers, we constructed a cohort comprising all singleton pregnancies without chromosomal abnormalities continuing to at least 20 completed weeks gestation in Denmark, 1977–2011. We then identified both pregnancies complicated by offspring congenital heart defects and those complicated by HDP (severe preeclampsia [PE]/eclampsia, moderate PE, gestational hypertension [GH]). Using polytomous logistic regression, we estimated odds ratios (ORs) for the association between carrying a fetus with a congenital heart defect and maternal risk of an HDP in the second half of pregnancy, overall and for specific heart defects. We also estimated ORs for the association between (1) an HDP in a previous pregnancy and the risk of carrying a child with a heart defect in subsequent pregnancies, and (2) fetal congenital heart defects in a previous pregnancy and the risk of HDP in subsequent pregnancies. Results Carrying a child with a heart defect was associated with a 3-fold increase in the risk of severe PE later in pregnancy (OR 3.02, 95% confidence interval [CI] 2.71–3.37) and a modest increase in the risk of moderate PE (OR 1.29, 95% CI 1.18–1.41), but not with the risk of GH (OR 1.08, 95% CI 0.93–1.25). These associations did not appear to depend on the type of offspring heart defect. Having a child with a heart defect in a previous pregnancy was also associated with PE (severe PE: OR 1.57, 95% CI 1.24–1.97; moderate PE: OR 1.32, 95% CI 1.16–1.51) but not with GH (OR 1.00, 95% CI 0.82–1.22) in subsequent pregnancies. Similarly, a history of PE in a previous pregnancy, but not of GH alone, was associated with an increased risk of offspring heart defects in later pregnancies (severe PE: OR 1.46, 95% CI 1.21–1.77; moderate PE: OR 1.13, 95% CI 1.01–1.27; GH: OR 1.12, 95% CI 0.91–1.37). Conclusion Our findings suggest that the same pathophysiological mechanisms may be involved in both congenital heart defects and severe PE (but are less important in less severe forms of HDP), and that these processes are most likely maternal, rather than fetal.

Objective To examine associations between rs9883204 in ADCY5 and rs900400 near LEKR1 and CCNL1 with birth weight in a preterm population. Both markers were associated with birth weight in a term population in a recent genome-wide association study of Freathy et al. Study design A meta-analysis of mother and infant samples was performed for associations of rs900400 and rs9883204 with birth weight in 393 families from the US, 265 families from Argentina, and 735 mother–infant pairs from Denmark. Z -scores adjusted for infant sex and gestational age were generated for each population separately and regressed on allele counts. Association evidence was combined across sites by inverse-variance weighted meta-analysis. Results Each additional C allele of rs900400 ( LEKR1/CCNL1 ) in infants was marginally associated with a 0.069 SD lower birth weight (95% CI, −0.159 to 0.022; P = .068). This result was slightly more pronounced after adjusting for smoking ( P = .036). No significant associations were identified with rs9883204 or in maternal samples. Conclusions These results indicate the potential importance of this marker on birth weight regardless of gestational age.

Objective The investigators tested the hypothesis that maternal-fetal immune interactions could be important in initiating spontaneous labor onset by examining if labor was delayed when fetuses share maternal HLA antigen types. Study Design HLA antigen types A, B, and DR in 200 Danish mother-infant pairs delivering in 42–44 weeks (postterm) were compared with 195 mother-infant pairs delivering in 37–40 weeks (term). Results Sharing of HLA A and B antigens was more common than expected in postterm deliveries. Odds ratios were 1.54 (95% confidence interval [CI], 1.01–2.35) and 1.75 (95% CI, 0.87–3.52), respectively (risk per shared antigen: 1.40 [95% CI, 1.04–1.90] per unit increase). Adding stringent birth-length criteria for postmaturity (92 cases; 168 controls) strengthened risks associated with antigen sharing to 1.57 (95% CI, 0.90–2.74) and 2.60 (95% CI, 1.15–5.88), respectively (risk per shared antigen: 1.60 (95% CI, 1.10–2.32). Conclusion Postterm-delivered infants had more HLA A and B antigens in common with their mothers, suggesting that recognition of HLA antigen differences by adaptive immunity may have a role in triggering labor onset.