Cardiovascular disease in rheumatoid arthritis : risk factors, clinical presentation, treatment and prognosis

It is well known that patients with rheumatoid arthritis (RA) are at increased risk of developing or dying from cardiovascular disease (CVD). There are several important questions remaining regarding the association between RA and specific CVDs. In this work, we have identified gaps in the existing knowledge and translated them into the objectives of the four sub-studies included in this thesis, which all focus on clinical aspects of CVD in RA. Several studies have assessed potential risk factors for CVD overall in RA, whereas no previous study has investigated the impact of RA-related factors on the risk of clinically significant acute coronary syndrome (ACS) in contemporary RA-patients. Existing results are thereby difficult to extrapolate into clinical praxis. Using a nested case-control design, we therefore aimed in Study I to investigate risk factors for ACS in new-onset RA. We found that laboratory measures of high inflammatory activity, clinical markers of high disease activity as well as poorer perceived health and a high number of sick days already during the first year following RA-onset were associated with an increased risk of ACS in RA. Seropositivity for the autoantibody rheumatoid factor (RF) was not associated with ACS, whereas antibodies towards citrullinated peptides (ACPAs) and in particular high positive levels of ACPAs was associated with an increased risk of ACS. Thus, the increased risk of ACS in patients with RA seems to be, at least partly, driven by inflammatory activity. Inflammation is known to affect the extent and composition of atherosclerosis, why the clinical phenotype of ACS in RA might differ compared with non-RA patients. However, little is known about the actual clinical phenotype, its treatment, follow-up care and outcomes of ACS in RA. For this reason, we investigated clinical ACS characteristics, short- and long-term outcomes and the usage of gold standard secondary preventive drugs in 1,135 RA-patients with ACS compared to 3,184 non-RA patients with ACS in Studies II and III. Our results indicated that patients with RA suffer from more severe ACS compared with non-RA patients. Furthermore, patients with RA also suffer from an increased risk of developing recurrent events or dying after the ACS. Usage of secondary preventive drugs was not substantially different in patients with RA compared with non-RA patients, and did not seem to explain the impaired prognosis following ACS. In the fourth and final study, we focused on assessing the relative risk (RR) of heart failure (HF) in RA, which, despite the known involvement of inflammation in the pathogenesis of HF, has only been assessed in a few studies. In Study IV, we estimated the relative risk (RR) of HF in RA both in the presence and absence of ischemic heart disease (IHD) in patients with new-onset RA and patients with established RA compared with non-RA patients. We also investigated the impact of RA-related inflammation on the risk of HF in patients with new-onset RA. We found that the risk of both ischemic and nonischemic HF was increased in RA. The risk increase, in particular for nonischemic HF, developed early after RA-onset and was associated with high inflammatory activity. The results of the four studies emphasize the importance of early disease control in RA, suggest that RA comorbidity should be acknowledged when risk stratifying ACS patients and also point out the importance of observing and investigating clinical signs of HF in patients with RA

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

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 theywere 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 individualswere 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, obsessivecompulsive 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 CDwas 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