Associations between rheumatoid arthritis, incident heart failure, and left ventricular ejection fraction.

BACKGROUND: Rheumatoid arthritis (RA) is an independent risk factor for heart failure (HF). Yet, the association between RA and left ventricular ejection fraction (LVEF) in incident HF is not well studied, nor are outcomes of HF in RA by LVEF. METHODS: We identified incident HF patients between 2003 and 2018 through the Swedish Heart Failure Registry, enriched with data from national health registers. Using logistic regression, associations between a prior diagnosis of RA and LVEF among HF patients and vs age, sex, and geographical area matched general population controls without HF were assessed. Additionally, associations between HF with vs without a prior diagnosis of RA, by LVEF, and outcomes up to 5 years after HF diagnosis were investigated using Cox regression. LVEF was primarily dichotomized at 40% and secondarily categorized as <40%, 40% to 49%, and ≥50%. Covariates included demographics and cardiovascular comorbidities. RESULTS: Among 20,916 incident HF patients, 331 (1.6%) had RA vs 1,047/103,501 (1.0%) of HF-free controls. The odds ratio (OR) for RA was 1.4 (95% CI: 1.1-1.8) in LVEF<40% vs HF-free controls and 1.6 (95% CI: 1.3-2.0) in LVEF≥40% vs HF-free controls. Among HF patients, RA was more common in HF with LVEF ≥40% (1.9%) vs LVEF<40% (1.3%), corresponding to OR 1.4 (95% CI: 1.1-1.7). No associations between RA and cardiovascular outcomes were observed across LVEF. An association between RA and all-cause mortality was observed only for patients with LVEF<40% (hazard ratio: 1.4; 95% CI: 1.1-1.8). CONCLUSIONS: RA was independently associated with incident HF, particularly HF with LVEF≥40%. RA did not associate with cardiovascular outcomes following HF diagnosis but was associated with increased risk of all-cause mortality in HF with LVEF<40%.

Maternal suicide attempts and deaths in the first year after cesarean delivery.

BACKGROUND: Cesarean delivery (CD) has been associated with postpartum psychiatric disorders, but less is known about the risk of suicidal behaviors. We estimated the incidence and risk of suicide attempts and deaths during the first postpartum year in mothers who delivered via CD v. vaginally. METHOD: All deliveries in Sweden between 1973 and 2012 were identified. The mothers were followed since delivery for 12 months or until the date of one of the outcomes (i.e. suicide attempt or death by suicide), death by other causes or emigration. Associations were estimated using Cox proportional hazards regression models. RESULTS: Of 4 016 789 identified deliveries, 514 113 (12.8%) were CDs and 3 502 676 (87.2%) were vaginal deliveries. During the 12-month follow-up, 504 (0.098%) suicide attempts were observed in the CD group and 2240 (0.064%) in the vaginal delivery group (risk difference: 0.034%), while 11 (0.0037%) deaths by suicide were registered in the CD group and 109 (0.0029%) in the vaginal delivery group (risk difference: 0.008%). Compared to vaginal delivery, CD was associated with an increased risk of suicide attempts [hazard ratio (HR) 1.46; 95% CI 1.32-1.60], but not of deaths by suicide (HR 1.44; 95% CI 0.88-2.36). CONCLUSIONS: Maternal suicidal behaviors during the first postpartum year were uncommon in Sweden. Compared to vaginal delivery, CD was associated with a small increased risk of suicide attempts, but not death by suicide. Improved understanding of the association between CD and maternal suicidal behaviors may promote more appropriate measures to improve maternal mental well-being and further reduce suicidal risks.

Maternal and fetal outcomes in acute hepatic porphyria: A Swedish National Cohort Study.

Current knowledge of pregnancy and perinatal outcomes in women with acute hepatic porphyria (AHP) is largely based on biochemical disease models, case reports, and case series. We performed a nationwide, registered-based cohort study to investigate the association between maternal AHP and the risk of adverse pregnancy and perinatal outcomes. All women in the Swedish Porphyria Register with confirmed AHP aged 18 years or older between 1987 and 2015 and matched general population comparators, with at least one registered delivery in the Swedish Medical Birth Register were included. Risk ratios (RRs) of pregnancy complications, delivery mode and perinatal outcomes were estimated and adjusted for maternal age at delivery, area of residency, birth year and parity. Women with acute intermittent porphyria (AIP), the most common form of AHP, were further categorized according to maximal lifetime urinary porphobilinogen (U-PBG) levels. The study included 214 women with AHP and 2174 matched comparators. Women with AHP presented with a higher risk for pregnancy-induced hypertensive disorder (aRR 1.73, 95% CI 1.12-2.68), gestational diabetes (aRR 3.41, 95% CI 1.69-6.89), and small-for-gestational-age birth (aRR 2.08, 95% CI 1.26-3.45). In general, RRs were higher among women with AIP who had high lifetime U-PBG levels. Our study shows an increased risk for pregnancy induced hypertensive disease, gestational diabetes, and small for gestational age births for AHP women, with higher relative risks for women with biochemically active AIP. No increased risk for perinatal death or malformations was observed.

Clinical characteristics and predictors of neonatal outcomes in chorioamnionitis at term gestation: A cohort study.

OBJECTIVE: To investigate the association between clinical and laboratory characteristics of chorioamnionitis in deliveries at term gestation with adverse neonatal outcomes. DESIGN: Retrospective cohort study. SETTING: The study is based on data from the Swedish Pregnancy Register, enriched with clinical data extracted from medical charts. SAMPLE: A cohort of 500 term singleton deliveries in Stockholm County with registered diagnosis of chorioamnionitis (based on the assessment of the responsible obstetrician) in the Swedish Pregnancy Register between 2014 and 2020. METHODS: Logistic regression was used to estimate odds ratios (ORs) as a measurement of the association between clinical and laboratory characteristics and neonatal complications. MAIN OUTCOME MEASURES: Neonatal infection and asphyxia-related complications. RESULTS: The prevalence of neonatal infection and asphyxia-related complications was 10% and 22%, respectively. First leukocyte count in the second tertile (OR 2.14, 95% CI 1.02-4.49), maximum C-reactive protein (CRP) level in the third tertile (OR 4.01, 95% Cl 1.66-9.68) and positive cervical culture (OR 2.22, 95% Cl 1.10-4.48) were associated with an increased risk of neonatal infection. Maximum level of CRP in the third tertile (OR 1.93, 95% Cl 1.09-3.41) and fetal tachycardia (OR 1.63, 95% Cl 1.01-2.65) were associated with an increased risk of asphyxia-related complications. CONCLUSIONS: Elevated inflammatory laboratory markers were associated with both neonatal infection and asphyxia-related complications, and fetal tachycardia was associated with asphyxia-related complications. Based on these findings, the incorporation of maternal CRP in the management of chorioamnionitis should be considered, and a continuous communication between obstetric and neonatal care extending past the delivery time point endorsed.

Treatment Strategies and Perforation Rate of Acute Appendicitis During the Early Phase of the COVID-19 Pandemic: A Swedish Cohort Study.

INTRODUCTION: It is unknown whether the COVID-19 pandemic has had an impact on emergency surgical care in Sweden. This study aimed to compare frequency, treatment strategies, severity, and complication rate of appendicitis during the initial phase of the COVID-19 pandemic with those of previous years. METHODS: In this single-center study, we identified all patients admitted with appendicitis between March 16 and June 16, 2020, at the Stockholm South General Hospital, and compared these with patients hospitalized with appendicitis during the same calendar period the three previous years. We used multivariate logistic regression to calculate Odds Ratios (OR) with 95% confidence intervals as measurement of the association between appendicitis treatment and perforation rate during the COVID-19 period compared to the nonCOVID-19 periods. RESULTS: In all, 892 patients hospitalized with appendicitis were identified, 241 (27%) in 2020 (Covid period group) and the remaining 651 (73%) during the same calendar periods 2017-2019 (nonCovid period group). Appendicitis during the COVID-19 period was associated with double the risk for undergoing conservative treatment (OR 2.15 [95% CI 1.44-3.21]), and a decreased risk for being diagnosed with perforated appendicitis (OR 0.68 [95% CI 0.48-0.98]). CONCLUSIONS: Patients admitted with appendicitis during the early phase of the COVID-19 pandemic in Stockholm, Sweden, were more likely to receive conservative treatment and less likely to suffer from perforated appendicitis compared to patients hospitalized before the pandemic. Hypothetically, this difference could have been due to pandemic-associated resource reallocation, or it may simply reflect an increasing trend towards conservative management of appendicitis.

Previous preterm cesarean delivery and risk of uterine rupture in subsequent trial of labor-a national cohort study.

BACKGROUND: Previous cesarean delivery is the major risk factor for uterine rupture in subsequent trial of labor. It has been suggested that a previous preterm cesarean delivery is associated with an increased risk of uterine rupture compared with a previous term cesarean delivery. However, the proposed association has only been investigated in a few studies and never in a study based on unselected contemporary prospectively collected data. OBJECTIVE: This study aimed to investigate the risk of uterine rupture among women attempting trial of labor after 1 previous preterm cesarean delivery compared with women with 1 previous term cesarean delivery. STUDY DESIGN: In this population-based cohort study, we used the Swedish Medical Birth Register between 1983 and 2016 and identified 9300 women with 1 previous preterm index cesarean delivery, 57,168 women with 1 previous term index cesarean delivery, and a second outcome delivery defined as trial of labor after 1 previous cesarean delivery. The risk of the main outcome uterine rupture and secondary outcomes placental abruption; placenta accreta spectrum; postpartum hemorrhage; blood transfusion; appearance, pulse, grimace, activity, and respiration of <7 at 5 minutes; neonatal cerebral dysfunction; and neonatal seizures were assessed using multivariate logistic regression models adjusted for potential confounders. RESULTS: Among women with a preterm index cesarean delivery, 102 (1.1%) had uterine rupture in the outcome delivery compared with 759 of women (1.4%) with term index cesarean delivery. This corresponded to a decreased risk of uterine rupture for women with preterm index cesarean delivery (odds ratio, 0.79; 95% confidence interval, 0.64-0.97), which did not remain significant in the analysis adjusted for maternal age, interdelivery interval, maternal body mass index, maternal height, induction of labor, postoperative infection after index cesarean delivery, and birthweight (odds ratio, 0.94; 95% confidence interval, 0.74-1.18). Stratifying by gestational week at index cesarean delivery (32+0 to 36+6 and <32+0 weeks' gestation) did not alter the main result. Stratifying by interdelivery interval revealed that women with a preterm index cesarean delivery were at a decreased risk of uterine rupture (odds ratio, 0.55 [95% confidence interval, 0.39-0.78]; adjusted odds ratio, 0.74 [95% confidence interval, 0.51-1.07]) in interdelivery intervals of >36 months whereas there were no significant differences within other time intervals. Of the secondary outcomes, 89 women (1.0%) with preterm index cesarean delivery were diagnosed as having placental abruption compared with 331 women (0.6%) with term index cesarean delivery, which corresponded to an approximately 60% increased risk (odds ratio, 1.66; 95% confidence interval, 1.31-2.10), which remained significant after adjusting for confounders (odds ratio, 1.49; 95% confidence interval, 1.13-1.96). Likewise, there was a slightly increased risk of postpartum hemorrhage for women with preterm index cesarean delivery (adjusted odds ratio, 1.12; 95% confidence interval, 1.02-1.24). There were no significant differences in the remaining secondary outcomes. CONCLUSION: The findings of this study suggest that preterm cesarean delivery is not associated with an increased risk of uterine rupture. Hence, women with 1 previous preterm cesarean delivery (with lower uterine segment incision) should receive medical management and counseling similar to women with previous term cesarean delivery before trial of labor after cesarean delivery.

Long-term outcomes and secondary prevention after acute coronary events in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of acute coronary syndrome (ACS) and suffer from poorer short-term outcomes after ACS. The aims of this study were to assess long-term outcomes in patients with RA with ACS compared with non-RA patients with ACS, and to investigate whether the use of secondary preventive drugs could explain any differences in ACS outcome. METHODS: We performed a cohort study based on 1135 patients with RA and 3184 non-RA patients who all developed an incident ACS between 2007 and 2010. We assessed 1-year and overall relative risks for ACS recurrence and mortality, as well as prescriptions of standard of care secondary preventive drugs. RESULTS: The risk of ACS recurrence, and of mortality, was increased in RA, both at 1 year after adjusting for baseline comorbidities (HR=1.30(95% CI 1.04 to 1.62) and 1.38(95% CI 1.20 to 1.59), respectively) and throughout the complete (mean 2 years) follow-up (HR=1.27(95% CI 1.06 to 1.52) and 1.50(95% CI 1.34 to 1.68), respectively). Among certain subgroups of ACS, there was a tendency of lower usage of statins, whereas there were no apparent differences in others. The increased rates of ACS recurrence and mortality remained in subgroup analyses of individuals whose prescription pattern indicated both adequate initiation and persistence to secondary preventive treatments. CONCLUSIONS: Patients with RA suffer from an increased risk of ACS recurrence and of death following ACS compared with general population, which in the present study could not readily be explained by differences in usage of secondary preventive drugs.

Rheumatoid arthritis is associated with a more severe presentation of acute coronary syndrome and worse short-term outcome.

AIMS: Despite a wealth of studies describing an increased incidence of acute coronary syndromes (ACSs) in rheumatoid arthritis (RA), considerably less is known about the clinical characteristics and their association with short-term outcome of such ACS. The aims of this study were therefore to investigate clinical characteristics and case-fatality rates following ACS in patients with RA. METHODS AND RESULTS: We compared the clinical presentation of incident ACS between 2007 and 2010 and their short-term mortality in a cohort of 1135 subjects with prevalent RA and in a cohort of 3184 matched general population comparators. Rheumatoid arthritis subjects more frequently presented with sudden cardiac death, ST-segment elevation myocardial infarctions, had higher levels of troponin and higher frequencies of in-hospital complications compared with the general population comparators. Furthermore, the short-term mortality was higher among RA-associated ACS (7-day hazard ratio (HR) = 1.65 [95% CI 1.32-2.08]; 30-day HR = 1.57 [95% CI 1.30-1.89]), which were somewhat attenuated but remained statistically significantly increased following adjustment for previous comorbidities, demographics, and educational level (7-day HR = 1.50 [95% CI 1.19-1.90]; 30-day HR = 1.43 [95% CI 1.18-1.72]), and for ACS type (7-day HR = 1.44 [95% CI 1.14-1.82]; 30-day HR = 1.36 [95% CI 1.13-1.64]). CONCLUSION: Patients with prevalent RA suffer more severe ACSs compared with the general population and also have poorer outcomes after the events, which can only partly be explained by increased event severity.

Occurrence and relative risk of stroke in incident and prevalent contemporary rheumatoid arthritis.

OBJECTIVE: In contrast with the wealth of data on ischaemic heart disease in rheumatoid arthritis (RA), data on stroke are scarce and contradictory. Despite the high clinical and aetiological relevance, there is no data regarding when (if ever) after RA diagnosis there is an increased risk. Our objective was to assess the risk of stroke (by subtype) in contemporary patients with RA, particularly in relation to time since RA diagnosis. METHODS: One incident RA cohort diagnosed between 1997 and 2009 (n=8077) and one nationwide prevalent RA cohort followed at Swedish rheumatology clinics between 2005 and 2009 ((n=39 065) were assembled). Each cohort member was matched to a general population comparator. Information on first-time hospitalisations for stroke up to 2009 was retrieved from the Swedish Patient Register. HR and 95% CI were estimated using Cox models. RESULTS: In prevalent unselected RA, the HR of ischaemic stroke was 1.29 (95% CI 1.18 to 1.41). In the incident RA cohort, the overall risk increase was small and non-significant (overall HR 1.11, 95% CI 0.95 to 1.30). When stratified by RA disease duration, an increased risk of ischaemic stroke was indeed detectable but only after 10 or more years since RA diagnosis (HR>10 years: 2.33, 95% CI 1.25 to 4.34). Risk of haemorrhagic stroke was increased in prevalent but not in incident RA. CONCLUSION: The magnitude of stroke risk is lower than for ischaemic heart disease in RA, and the evolvement of this risk from RA diagnosis may be slower. This suggests different driving forces behind these two RA co-morbidities and has implications for the clinical follow-up of patients with RA.

Pregnancy-Induced Hypertensive Disorder and Risks of Future Ischemic and Nonischemic Heart Failure.

BACKGROUND: Although adverse pregnancy outcomes are associated with an increased risk of cardiovascular disease, studies on timing and subtypes of heart failure after a hypertensive pregnancy are lacking. OBJECTIVES: The goal of this study was to assess the association between pregnancy-induced hypertensive disorder and risk of heart failure, according to ischemic and nonischemic subtypes, and the impact of disease characteristics and the timing of heart failure risks. METHODS: This was a population-based matched cohort study, comprising all primiparous women without a history of cardiovascular disease included in the Swedish Medical Birth Register between 1988 and 2019. Women with pregnancy-induced hypertensive disorder were matched with women with normotensive pregnancies. Through linkage with health care registers, all women were followed up for incident heart failure, classified as ischemic or nonischemic. RESULTS: In total, 79,334 women with pregnancy-induced hypertensive disorder were matched with 396,531 women with normotensive pregnancies. During a median follow-up of 13 years, rates of all heart failure subtypes were more common among women with pregnancy-induced hypertensive disorder. Compared with women with normotensive pregnancies, adjusted HRs (aHRs) with 95% CIs were as follows: heart failure overall, aHR: 1.70 (95% CI: 1.51-1.91); ischemic heart failure, aHR: 2.28 (95% CI: 1.74-2.98); and nonischemic heart failure, aHR: 1.60 (95% CI: 1.40-1.83). Disease characteristics indicating severe hypertensive disorder were associated with higher heart failure rates, and rates were highest within the first years after the hypertensive pregnancy but remained significantly increased thereafter. CONCLUSIONS: Pregnancy-induced hypertensive disorder is associated with an increased short-term and long-term risk of incident ischemic and nonischemic heart failure. Disease characteristics indicating more severe forms of pregnancy-induced hypertensive disorder amplify the heart failure risks.

Risk of venous thromboembolism in patients with rheumatoid arthritis and association with disease duration and hospitalization.

CONTEXT: Recent reports suggest that rheumatoid arthritis (RA) may be a risk factor for venous thromboembolism (VTE), particularly in conjunction with hospitalization. Using hospitalization data to identify RA and VTE may identify patients when they are at elevated risk for other reasons, obscuring the incompletely understood underlying association between RA and VTE and leading to inappropriate institution or timing of interventions. OBJECTIVE: To estimate risks for VTE in patients with RA, including the relation of these risks to disease duration and hospitalization. DESIGN, SETTING, AND PATIENTS: Prospective, population-based cohort study of 1 prevalent RA cohort (n = 37,856), 1 incident RA cohort (n = 7904), and matched general population comparison cohorts, all from Sweden, with follow-up from 1997 through 2010. MAIN OUTCOME MEASURE: First-time VTE. RESULTS: Patients with prevalent RA were at greater risk of VTE than the general population (rate, 5.9 [95% CI, 5.1-6.6] vs 2.8 [95% CI, 2.6-3.1] per 1000 person-years (adjusted hazard ratio [HR], 2.0 [95% CI, 1.9-2.2]; P < .001). By the time of RA symptom onset, there was no statistically significant association between a history of VTE and RA (odds ratio, 1.2 [95% CI, 1.0-1.4]; P = .08; 150 events in the RA cohort vs 587 in the comparison cohort). Counting from RA diagnosis, an increased rate in the RA cohort vs the comparison cohort (3.8 [95% CI, 2.5-5.2] vs 2.4 [95% CI, 1.9-2.9] per 1000 person-years; HR, 1.6 [95% CI, 1.1-2.5]; P = .02) was detected within the first year and did not increase further during the first decade. Although rates for VTE following hospitalization were higher, the 1-year rate of VTE per 1000 person-years was not higher in the RA cohort than in the comparison cohort after hospital discharge (11.8 [95% CI, 8.6-15.1] vs 13.1 [11.3-14.8]; HR, 1.0 [95% CI, 0.7-1.4]; P = .90). The rates of VTE increased with age but were largely similar across sex and rheumatoid factor status, as were the HRs for VTE across age, sex, and rheumatoid factor status. CONCLUSIONS: Compared with the general population, Swedish patients with RA had an elevated risk for VTE that was stable over the first 10 years after diagnosis. Although hospitalization was a risk factor for VTE the first year after discharge, the excess risk was not greater in patients with RA than in the general population.

Analysis of Neurodevelopmental Disorders in Offspring of Mothers With Eating Disorders in Sweden.

Importance: Despite indices of impaired neurodevelopment in children of mothers with eating disorders, it remains unclear whether these children are at increased risk of developing neuropsychiatric diseases. Objective: To evaluate the association between maternal eating disorders, whether preexisting or ongoing during pregnancy, and offspring neuropsychiatric disease risk. Design, Setting and Participants: This population-based prospective cohort study used the Swedish Medical Birth Registry and identified singleton births registered between from January 1, 1990, and December 31, 2012. Children of exposed mothers with eating disorders were matched with comparator children of mothers without diagnoses of eating disorders. To adjust for unmeasured shared familial factors, a cluster of exposed children with full maternal cousin comparators was identified. Follow-up was completed on December 31, 2017. Data were analyzed from August 31, 2020, to April 30, 2021. Exposures: Maternal eating disorder diagnosis. Main Outcomes and Measures: All children were followed up from 1 year of age for autism spectrum disorder (ASD) and from 3 years of age for attention-deficit/hyperactivity disorder (ADHD). The relative risk of ASD and ADHD was assessed among exposed children, stratified by eating disorder subtype and ongoing vs previous disease, adjusted for potential confounders, including parental socioeconomic status and comorbidities. Results: Among the 52 878 children included in the analysis, maternal eating disorder exposure (n = 8813) was associated with an increased risk of ADHD (hazard ratio [HR] for anorexia nervosa, 1.42 [95% CI, 1.23-1.63]; HR for bulimia nervosa, 1.91 [95% CI, 1.43-2.54]; and HR for unspecified eating disorder, 2.00 [95% CI, 1.72-2.32]) and ASD (HR for anorexia nervosa, 2.04 [95% CI, 1.58-2.63]; HR for bulimia nervosa, 2.70 [95% CI, 1.68-4.32]; and HR for unspecified eating disorder, 1.95 [95% CI, 1.49-2.54]). After adjustment for parental confounders, the risk of ADHD remained significantly increased, whereas the risk of ASD in children to mothers with bulimia nervosa was no longer significant. Ongoing anorexia nervosa was associated with a significantly higher risk of ADHD (HR, 2.52 [95% CI, 1.86-3.42]) and ASD (HR, 3.98 [95% CI, 2.49-6.27]) compared with previous disease (HRs, 1.26 [95% CI, 1.06-1.48] and 1.81 [95% CI, 1.38-2.38], respectively). Results based on the family cluster were similar to those of the main analysis for maternal exposure to anorexia nervosa and bulimia nervosa. Conclusions and Relevance: These findings suggest that children born to mothers with eating disorders, in particular disorders that were active during pregnancy, were at increased risk of developing ADHD and ASD. The association could not be fully explained by parental psychiatric comorbidities, and among children of mothers with anorexia nervosa and bulimia nervosa, it could not be explained by unmeasured familial confounding.

Findings on Coronary Angiographies in Patients With Rheumatoid Arthritis and Ischemic Heart Disease: Are They Different From Patients Without Rheumatoid Arthritis?

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of coronary artery disease (CAD) and seem to develop more severe acute coronary syndromes (ACS) than the general population. Because few studies have investigated the CAD distribution in the context of acute or stable CAD in RA, the objective was to investigate whether this risk is due to a different distribution and severity of coronary stenoses (versus non-RA), resulting in clinical manifestation of CAD. METHODS: We performed a population-based study using linkages of nationwide clinical, health, and demographics registers. We compared 1 cohort of patients with RA, and 1 matched cohort of patients without RA, undergoing a first coronary angiography from 2006 through 2015. Cardiovascular (CV) characteristics and the presence and distribution of clinically significant stenoses were compared (through odds ratios [ORs]), stratified by indication (stable CAD, ST-elevation myocardial infarction [STEMI], and non-ST-elevation ACS [NSTACS]), using logistic regression. RESULTS: We identified 2,985 patients with RA and 10,290 patients without RA who underwent a first coronary angiography. A higher proportion of patients with RA (75% versus 69%) had STEMI and NSTACS as indication for angiography. We found no difference in the presence and distribution of clinically significant coronary stenoses in RA compared with the patients without RA, regardless of the CAD type (for having any significant stenosis in stable CAD OR 0.9, STEMI OR 0.8, and NSTACS OR 1.1), stratification by RA duration, sex, or burden of concomitant CV risk factors. CONCLUSION: Although RA may accelerate the development of clinical CAD events, the underlying angiographic characteristics are similar to those in patients without RA.

Characteristics and outcome of a first acute myocardial infarction in patients with ankylosing spondylitis.

OBJECTIVES: To study clinical characteristics, mortality, and secondary prevention, after a first incident acute myocardial infarction (AMI) in patients with ankylosing spondylitis (AS) compared with the general population. METHODS: In total, 292 subjects with AS and a first AMI between Jan 2006 and Dec 2014 were identified using the Swedish national patient register. Each subject was matched with up to 5 general population comparators per AS-patient (n = 1276). Follow-up started at the date of admission for AMI and extended until death or 365 days of follow-up. Cox regression was used to assess mortality in two time intervals: days 0-30 and days 31-365. For a subgroup with available data, clinical presentation at admission, course, treatment for AMI, and secondary prevention were compared. RESULTS: During the 365-day follow-up, 56/292 (19%) AS patients and 184/1276 (14%) comparators died. There were no difference in mortality due to cardiovascular-related causes, although the overall mortality day 31-365 was increased among patients with AS compared with comparators (HR [95% CI] = 2.0 [1.3;3.0]). At admission, AS patients had a higher prevalence of cardiovascular comorbidities compared with comparators. At discharge, patients with AS were less often prescribed lipid-lowering drugs and non-aspirin antiplatelet therapy. CONCLUSIONS: Patients with AS tend to have a higher comorbidity burden at admission for first AMI. The mortality after a first AMI due to cardiovascular-related causes does not seem to be elevated, despite an increased overall mortality during days 31-365 among patients with AS compared with the general population. Key Points • The all-cause mortality after a first AMI was higher in patients with AS. • Mortality after a first AMI due to CVD-related causes does not seem to be elevated for patients with AS. • In patients with AS suffering a first AMI, more attention should be given to other comorbidities causing an excess in mortality.

Assessment of Cesarean Delivery and Neurodevelopmental and Psychiatric Disorders in the Children of a Population-Based Swedish Birth Cohort.

Importance: Recent studies suggest that cesarean delivery (CD) is associated with increased risk of neurodevelopmental disorders in children, although they were unable to control for indications for CD or familial confounding beyond full siblings. Objective: To examine the association between CD and neurodevelopmental and psychiatric disorders in children. Design, Setting, and Participants: This Swedish register-based cohort study included 1 179 341 term-birth singletons born between January 1, 1990, and December 31, 2003, and followed up through December 31, 2013. All individuals were linked to their full siblings, maternal and paternal half siblings, and maternal full cousins. Statistical analyses were performed from September 26, 2019, to January 16, 2021. Exposures: Birth by CD recorded at birth, stratified into planned and intrapartum CD. Main Outcomes and Measures: Registered diagnoses of neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), intellectual disability, tic disorders, communication disorders, learning disorders, and any neurodevelopmental disorder; and psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, depressive disorders, eating disorders, bipolar disorders, psychotic disorders, and any psychiatric disorder. Results: Of 1 179 341 individuals, 1 048 838 (533 140 boys [50.8%]) were delivered vaginally, 59 514 (30 138 boys [50.6%]) were delived via planned CD, and 70 989 (39 191 boys [55.2%]) were delivered via intrapartum CD. Mean (SD) age at follow-up was 17.7 (4.1) years for vaginal delivery, 16.6 (4.2) years for planned CD, and 16.8 (4.1) years for intrapartum CD. Compared with vaginal delivery, and after controlling for measured covariates (parental and neonatal characteristics, maternal comorbidities, and pregnancy complications), CD was associated with higher risk in children of any neurodevelopmental disorder (planned CD, hazard ratio [HR], 1.17; 95% CI, 1.13-1.22; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.14), ADHD (planned CD, HR, 1.17; 95% CI, 1.12-1.23; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.15), and intellectual disability (planned CD, HR, 1.26; 95% CI, 1.14-1.39; intrapartum CD, HR, 1.17; 95% CI, 1.06-1.28). Only planned CD was associated with a higher risk of ASD (HR, 1.20; 95% CI, 1.10-1.31), communication disorders (HR, 1.14; 95% CI, 1.02-1.28), and learning disorders (HR, 1.15; 95% CI, 1.01-1.30). Cesarean delivery was not associated with the remaining disorders. The associations between CD and any neurodevelopmental disorder, ADHD, ASD, and intellectual disability attenuated in full cousins and paternal half siblings, and further attenuated (became nonsignificant) in maternal half siblings and full siblings (risk of any neurodevelopmental disorder in full siblings, planned CD, HR, 0.93; 95% CI, 0.81-1.06; intrapartum CD, HR, 1.07; 95% CI, 0.96-1.21). Conclusions and Relevance: The findings of this study suggest that the association between CD and increased risk of neurodevelopmental disorders in the children was most likely explained by unmeasured familial confounding.

Association of Maternal Eating Disorders With Pregnancy and Neonatal Outcomes.

Importance: The prevalence of eating disorders is high among women of reproductive age, yet the association of eating disorders with pregnancy complications and neonatal health has not been investigated in detail, to our knowledge. Objective: To investigate the relative risk of adverse pregnancy and neonatal outcomes for women with eating disorders. Design, Setting, and Participants: This population-based cohort study included all singleton births included in the Swedish Medical Birth Register from January 1, 2003, to December 31, 2014. A total of 7542 women with eating disorders were compared with 1 225 321 women without eating disorders. Statistical analysis was performed from January 1, 2018, to April 30, 2019. Via linkage with the national patient register, women with eating disorders were identified and compared with women free of any eating disorder. Eating disorders were further stratified into active or previous disease based on last time of diagnosis. Main Outcomes and Measures: The risk of adverse pregnancy outcomes (hyperemesis, anemia, preeclampsia, and antepartum hemorrhage), the mode of delivery (cesarean delivery, vaginal delivery, or instrumental vaginal delivery), and the neonatal outcomes (preterm birth, small and large sizes for gestational age, Apgar score <7 at 5 minutes, and microcephaly) were calculated using Poisson regression analysis to estimate risk ratios (RRs). Models were adjusted for age, parity, smoking status, and birth year. Results: There were 2769 women with anorexia nervosa (mean [SD] age, 29.4 [5.3] years), 1378 women with bulimia nervosa (mean [SD] age, 30.2 [4.9] years), and 3395 women with an eating disorder not otherwise specified (EDNOS; mean [SD] age, 28.9 [5.3] years), and they were analyzed and compared with 1 225 321 women without eating disorders (mean [SD] age, 30.3 [5.2] years). All subtypes of maternal eating disorders were associated with an approximately 2-fold increased risk of hyperemesis during pregnancy (anorexia nervosa: RR, 2.1 [95% CI, 1.8-2.5]; bulimia nervosa: RR, 2.1 [95% CI, 1.6-2.7]; EDNOS: RR, 2.6 [95% CI, 2.3-3.0]). The risk of anemia during pregnancy was doubled for women with active anorexia nervosa (RR, 2.1 [95% CI, 1.3-3.2]) or EDNOS (RR, 2.1 [95% CI, 1.5-2.8]). Maternal anorexia nervosa was associated with an increased risk of antepartum hemorrhage (RR, 1.6 [95% CI, 1.2-2.1]), which was more pronounced in active vs previous disease. Women with anorexia nervosa (RR, 0.7 [95% CI, 0.6-0.9]) and women with EDNOS (RR, 0.8 [95% CI, 0.7-1.0]) were at decreased risk of instrumental-assisted vaginal births; otherwise, there were no major differences in mode of delivery. Women with eating disorders, all subtypes, were at increased risk of a preterm birth (anorexia nervosa: RR, 1.6 [95% CI, 1.4-1.8]; bulimia nervosa: RR, 1.3 [95% CI, 1.0-1.6]; and EDNOS: RR, 1.4 [95% CI, 1.2-1.6]) and of delivering neonates with microcephaly (anorexia nervosa: RR, 1.9 [95% CI, 1.5-2.4]; bulimia nervosa: RR, 1.6 [95% CI, 1.1-2.4]; EDNOS: RR, 1.4 [95% CI, 1.2-1.9]). Conclusions and Relevance: The findings of this study suggest that women with active or previous eating disorders, regardless of subtype, are at increased risk of adverse pregnancy and neonatal outcomes and may need increased surveillance in antenatal and delivery care.

Association Between Rheumatoid Arthritis and Risk of Ischemic and Nonischemic Heart Failure.

BACKGROUND: It is unknown whether the increased risk of heart failure (HF) in rheumatoid arthritis (RA) is independent of ischemic heart disease (IHD). OBJECTIVES: This study sought to investigate the relative risk of HF overall and by subtype (ischemic and nonischemic HF) in patients with RA and to assess the impact of RA disease factors. METHODS: Two contemporary cohorts of RA subjects were identified from Swedish patient and rheumatology registries and matched 1:10 to general population comparator subjects. A first-ever HF diagnosis (classified as ischemic HF or nonischemic HF based on the presence of IHD) was assessed through registry linkages. Relative risks for a history of HF before RA onset were calculated through odds ratios. Relative risks of incident HF in RA were calculated as hazard ratios (HRs). RESULTS: By the time of RA onset, a history of HF was not more common in RA. In the new-onset RA cohort, the overall HRs for subsequent HF (any type), ischemic HF, and nonischemic HF were between 1.22 and 1.27. The risk of nonischemic HF increased rapidly after RA onset, in contrast to the risk of ischemic HF. High disease activity was associated with all HF types but was most pronounced for nonischemic HF. In the cohort of patients with RA of any duration, the HRs were between 1.71 and 1.88 for the different HF subtypes. CONCLUSIONS: Patients with RA are at increased risk of HF that cannot be explained by their increased risk of IHD. The increased risk of nonischemic HF occurred early and was associated with RA severity.

Risk factors for the rapid increase in risk of acute coronary events in patients with new-onset rheumatoid arthritis: a nested case-control study.

OBJECTIVE: To investigate risk factors for acute coronary syndrome (ACS) in patients with new-onset rheumatoid arthritis (RA). METHODS: We performed a nested case-control study of patients with incident RA included in the Epidemiological Investigation of RA study. Cases with ACS were identified using Swedish national health registers and matched with up to 5 controls without ACS, based on incidence density-based sampling. Information on potential exposures (clinical disease activity, serologic features, genetic markers, comorbidities, pharmacotherapies, and sick leave) was collected from medical charts and register-based sources. RESULTS: We identified 138 cases and 624 controls. Smoking, history of myocardial infarction, and >50 days of sick leave the year following RA onset were associated with an increased risk of ACS. Area under the curve measurements of C-reactive protein level, erythrocyte sedimentation rate, Disease Activity Score in 28 joints (DAS28), and global health in the upper tertile during the first year and the complete followup period were both strongly associated with an increased risk of ACS. Treatment with disease-modifying antirheumatic drugs did not alter the ACS risk, nor did the presence of rheumatoid factor (RF) or shared epitope alleles, whereas high anti-citrullinated protein antibody (ACPA) levels were borderline significantly associated with ACS risk. CONCLUSION: In this study of risk factors for ACS in incident RA, clinical markers of inflammatory activity, disease activity, and total number of days of sick leave and disability pension during the first year following RA onset were identified as ACS risk factors. We found no association with RF, which was previously linked to cardiovascular disease risk in RA, but there was a borderline significant association with high ACPA levels.