Low testosterone levels are predictive for incident atrial fibrillation and ischaemic stroke in men, but protective in women – results from the FINRISK study

Background Atrial fibrillation is the most common serious abnormal heart rhythm, and a frequent cause of ischaemic stroke. Recent experimental studies, mainly in orchiectomised rats, report a relationship between sex hormones and atrial electrophysiology and electroanatomy. We aimed to evaluate whether low testosterone levels are predictive for atrial fibrillation and/or ischaemic stroke in men and women. Design and methods The serum total testosterone levels were measured at baseline in a population cohort of 7892 subjects (3876 male, 4016 female), aged 25–74 years, using a commercially available immunoassay. The main outcome measure was atrial fibrillation or ischaemic stroke, whichever came first. Results During a median follow-up of 13.8 years, a total of 629 subjects (8.0%) suffered from incident atrial fibrillation ( n = 426) and/or ischemic stroke ( n = 276). Cox regression analyses, adjusted for age (used as time-scale), geographical region, total cholesterol (log), high-density lipoprotein-cholesterol (log), hypertension medication, known diabetes, smoking status, waist-hip-ratio, and time of blood drawn, documented differential predictive value of low sex-specific testosterone levels for atrial fibrillation and/or ischaemic stroke, in men and in women: Increasing levels were associated with lower risk in men (hazard ratio per one nmol/l increase 0.98 (95% confidence interval 0.93–1.00); p = 0.049). On the other hand, increasing testosterone levels were associated with higher risk in women (hazard ratio per one nmol/l increase 1.17 (95% confidence interval 1.02–1.36); p = 0.031). Conclusion Our study indicates that low testosterone levels are associated with increased risk of future atrial fibrillation and/or ischaemic stroke in men, while they are protective in women.

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Physical activity modifies the risk of atrial fibrillation in obese individuals: The HUNT3 study

European Journal of Preventive Cardiology ◽

10.1177/2047487318784365 ◽

2018 ◽

Vol 25 (15) ◽

pp. 1646-1652 ◽

Cited By ~ 14

Author(s):

Lars E Garnvik ◽

Vegard Malmo ◽

Imre Janszky ◽

Ulrik Wisløff ◽

Jan P Loennechen ◽

...

Keyword(s):

Physical Activity ◽

Atrial Fibrillation ◽

Body Mass Index ◽

Confidence Interval ◽

Body Mass ◽

High Body Mass Index ◽

Overweight And Obesity ◽

Hazard Ratio ◽

Increased Risk

Background Atrial fibrillation is the most common heart rhythm disorder, and high body mass index is a well-established risk factor for atrial fibrillation. The objective of this study was to examine the associations of physical activity and body mass index and risk of atrial fibrillation, and the modifying role of physical activity on the association between body mass index and atrial fibrillation. Design The design was a prospective cohort study. Methods This study followed 43,602 men and women from the HUNT3 study in 2006–2008 until first atrial fibrillation diagnosis or end of follow-up in 2015. Atrial fibrillation diagnoses were collected from hospital registers and validated by medical doctors. Cox proportional hazard regression analysis was performed to assess the association between physical activity, body mass index and atrial fibrillation. Results During a mean follow-up of 8.1 years (352,770 person-years), 1459 cases of atrial fibrillation were detected (4.1 events per 1000 person-years). Increasing levels of physical activity were associated with gradually lower risk of atrial fibrillation ( p trend 0.069). Overweight and obesity were associated with an 18% (hazard ratio 1.18, 95% confidence interval 1.03–1.35) and 59% (hazard ratio 1.59, 95% confidence interval 1.37–1.84) increased risk of atrial fibrillation, respectively. High levels of physical activity attenuated some of the higher atrial fibrillation risk in obese individuals (hazard ratio 1.53, 95% confidence interval 1.03–2.28 in active and 1.96, 95% confidence interval 1.44–2.67 in inactive) compared to normal weight active individuals. Conclusion Overweight and obesity were associated with increased risk of atrial fibrillation. Physical activity offsets some, but not all, atrial fibrillation risk associated with obesity.

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Prognostic significance of patent foramen ovale in anticoagulated patients with atrial fibrillation

Open Heart ◽

10.1136/openhrt-2019-001229 ◽

2020 ◽

Vol 7 (1) ◽

pp. e001229

Author(s):

Rowlens M Melduni ◽

Waldemar E Wysokinski ◽

Zhenzhen Wang ◽

Bernard J Gersh ◽

Samuel J Asirvatham ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Patent Foramen Ovale ◽

Cox Regression ◽

Prognostic Significance ◽

Multivariable Analysis ◽

Contrast Study ◽

Foramen Ovale ◽

Obstructive Sleep ◽

Increased Risk

ObjectivePrevious studies have postulated a causal role of patent foramen ovale (PFO) in the aetiology of embolic stroke in the general population. We hypothesised that the presence of concomitant PFO and atrial fibrillation (AF) will add incremental risk of ischaemic stroke to that linked to AF alone.MethodsWe analysed data on 3069 consecutive patients (mean age 69.4±12.2 years; 67.1% men) undergoing transoesophageal echocardiography-guided electrical cardioversion (ECV) for AF between May 2000 and March 2012. PFO was identified by colour Doppler and agitated saline contrast study. All patients were followed up after ECV for first documentation of ischaemic stroke. Outcomes were compared using Cox regression models.ResultsThe prevalence of PFO was 20.0% and the shunt direction was left-to-right in the majority of patients (71.4%). Patients with PFO had a higher frequency of obstructive sleep apnoea (21.7% vs 17.1%, p=0.01) and higher mean peak left atrial appendage emptying velocity (38.3±21.8 vs 36.1±20.4 cm/s; p=0.04) compared with those without PFO. Otherwise, baseline characteristics were similar between groups. During a mean follow-up period of 7.3±4.6 years, 214 patients (7.0%) had ischaemic stroke. Multivariable analysis showed no significant association between PFO and ischaemic stroke (HR, 0.82 (95% CI 0.57 to 1.18)). PFO shunt direction was strongly associated with stroke: HR, 1.91 (95% CI 1.16 to 3.16) for right-to-left shunt and HR, 0.58 (95% CI 0.36 to 0.93) for left-to-right shunt.ConclusionsThe presence of concurrent PFO in this largely anticoagulated group of patients with AF was not associated with increased risk of ischaemic stroke.

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Testosterone and glucose metabolism in men: current concepts and controversies

Journal of Endocrinology ◽

10.1530/joe-13-0393 ◽

2013 ◽

Vol 220 (3) ◽

pp. R37-R55 ◽

Cited By ~ 54

Author(s):

Mathis Grossmann

Keyword(s):

Insulin Resistance ◽

Body Composition ◽

Glucose Metabolism ◽

Metabolic Disorders ◽

Experimental Studies ◽

Diabetic Control ◽

Testosterone Levels ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Low Testosterone

A wealth of observational studies show that low testosterone is associated with insulin resistance and with an increased risk of diabetes and the metabolic syndrome. Experimental studies have identified potential mechanisms by which low testosterone may lead to insulin resistance. Visceral adipose tissue is an important intermediate in this relationship. Actions of testosterone or its metabolite oestradiol on other tissues such as muscle, liver, bone or the brain, and body composition-independent effects may also play a role. However, definitive evidence from randomised controlled trials (RCTs) to clarify whether the association of low testosterone with disordered glucose metabolism is causative is currently lacking. It therefore remains possible that this association is due to reverse causation, or simply originates by association with common health and lifestyle factors. RCTs of testosterone therapy in men with or without diabetes consistently show modest metabolically favourable changes in body composition. Despite this, testosterone effects on glucose metabolism have been inconsistent. Recent evidence suggests that the hypothalamic–pituitary–testicular axis suppression in the majority of obese men with metabolic disorders is functional, and may be, at least in part, reversible with weight loss. Until further evidence is available, lifestyle measures with emphasis on weight reduction, treatment of comorbidities and optimisation of diabetic control should remain the first-line treatment in these men. Such measures, if successful, may be sufficient to normalise testosterone levels in men with metabolic disorders, who typically have only modest reductions in circulating testosterone levels.

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Incident Atrial Fibrillation and the Risk of Stroke in Adults with Chronic Kidney Disease

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.04060318 ◽

2018 ◽

Vol 13 (9) ◽

pp. 1314-1320 ◽

Cited By ~ 11

Author(s):

Juan Jesus Carrero ◽

Marco Trevisan ◽

Manish M. Sood ◽

Peter Bárány ◽

Hong Xu ◽

...

Keyword(s):

Atrial Fibrillation ◽

Confidence Interval ◽

Stroke Risk ◽

Cox Regression ◽

Hazard Ratio ◽

Competing Risk ◽

Cox Regression Analysis ◽

Diagnostic Codes ◽

Lower Egfr ◽

Therapeutic Procedures

Background and objectivesPatients with CKD have a high risk of atrial fibrillation. Both CKD and atrial fibrillation are associated with higher risk of stroke and death. However, the effect of incident atrial fibrillation on stroke risk among patients with CKD is unknown.Design, setting, participants, & measurementsOur study included adults with CKD (eGFR<60 ml/min per 1.73 m2) without previously documented atrial fibrillation who had been in contact with health care in Stockholm, Sweden during 2006–2011. Incident atrial fibrillation was identified by administrative diagnostic codes in outpatient or inpatient care and treated as a time-updated exposure in the analysis of stroke and death risk. Stroke events and deaths were ascertained from regional and national registers with complete coverage. Covariates included demographics, comorbidities, therapeutic procedures, and medications. Multivariable Cox regression analysis and competing risk analysis (accounting for death) were used to estimate the association between incident atrial fibrillation and stroke.ResultsAmong 116,184 adults with CKD, 13,412 (12%) developed clinically recognized atrial fibrillation during a mean follow-up of 3.9 years (interquartile range, 2.3–5.7 years). Incidence of atrial fibrillation increased across lower eGFR strata: from 29.4 to 46.3 atrial fibrillations per 1000 person-years in subjects with eGFR=45–60 and <30 ml/min per 1.73 m2, respectively; 1388 (53.8 per 1000 person-years) cases of stroke and 5592 (205.1 per 1000 person-years) deaths occurred after incident atrial fibrillation compared with 6850 (16.6 per 1000 person-years) cases of stroke and 28,613 (67.5 per 1000 person-years) deaths during periods without atrial fibrillation. After adjustment, incident atrial fibrillation was associated with higher risk of stroke (hazard ratio, 2.00; 95% confidence interval, 1.88 to 2.14) and death (hazard ratio, 1.76; 95% confidence interval, 1.71 to 1.82). This was attributed to both ischemic stroke (hazard ratio, 2.11; 95% confidence interval, 1.96 to 2.28) and intracranial bleeds (hazard ratio, 1.64; 95% confidence interval, 1.42 to 1.90). Stroke risk was similar across all eGFR strata. In competing risk analyses accounting for death, the association between incident atrial fibrillation and stroke was attenuated but remained higher (subhazard ratio, 1.49; 95% confidence interval, 1.39 to 1.60).ConclusionsPatients with CKD who develop atrial fibrillation are at higher risk of stroke and death.

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Associations of anger, vital exhaustion, anti-depressant use, and poor social ties with incident atrial fibrillation: The Atherosclerosis Risk in Communities Study

European Journal of Preventive Cardiology ◽

10.1177/2047487319897163 ◽

2020 ◽

pp. 204748731989716 ◽

Cited By ~ 2

Author(s):

Parveen K Garg ◽

J’Neka S Claxton ◽

Elsayed Z Soliman ◽

Lin Y Chen ◽

Tené T Lewis ◽

...

Keyword(s):

Atrial Fibrillation ◽

Confidence Interval ◽

Sex Education ◽

Social Ties ◽

Hazard Ratio ◽

Atherosclerosis Risk In Communities ◽

Vital Exhaustion ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Study Participants

Background We examined the relationships of anger, vital exhaustion, anti-depressant use, and poor social ties with incident atrial fibrillation in a biracial cohort of middle and older-aged adults. Methods This analysis included 11,445 Atherosclerosis Risk in Communities Study participants who were free of atrial fibrillation at baseline in 1990–1992. Vital exhaustion was assessed at baseline and defined as a score in the highest quartile on the 21-item Vital Exhaustion Questionnaire. Baseline anti-depressant use was self-reported. The Spielberger Trait Anger Scale to assess anger and both the Interpersonal Support Evaluation List and the Lubben Social Network Scale to assess social ties were also administered at baseline. The primary outcome was incident atrial fibrillation throughout 2016, identified by electrocardiogram, hospital discharge coding of atrial fibrillation, and death certificates. Results A total of 2220 incident atrial fibrillation cases were detected over a median follow-up of 23.4 years. After adjusting for age, race-center, sex, education, and height, participants in the 4th Vital Exhaustion Questionnaire quartile (referent = 1st Vital Exhaustion Questionnaire quartile) and those reporting anti-depressant use were at increased risk for atrial fibrillation (hazard ratio = 1.45, 95% confidence interval 1.29–1.64 for Vital Exhaustion Questionnaire; hazard ratio = 1.37, 95% confidence interval 1.11–1.69 for anti-depressant use). The increased atrial fibrillation risk observed for 4th Vital Exhaustion Questionnaire quartile participants remained significant after additional adjustment for relevant comorbidities (hazard ratio = 1.20; confidence interval 1.06–1.35). No significant associations were observed for anger or poor social ties with development of atrial fibrillation. Conclusions Vital exhaustion is associated with an increased risk of incident atrial fibrillation.

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Migraine with visual aura is a risk factor for incident atrial fibrillation

Neurology ◽

10.1212/wnl.0000000000006650 ◽

2018 ◽

Vol 91 (24) ◽

pp. e2202-e2210 ◽

Cited By ~ 24

Author(s):

Souvik Sen ◽

X. Michelle Androulakis ◽

Viktoriya Duda ◽

Alvaro Alonso ◽

Lin Yee Chen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Confidence Interval ◽

Stroke Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Visual Aura ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk

ObjectiveMigraine with visual aura is associated with cardioembolic stroke risk. The aim of this study was to test association between migraine with visual aura and atrial fibrillation (AF), in the Atherosclerosis Risk in Communities study.MethodsIn the Atherosclerosis Risk in Communities study, a longitudinal, community-based cohort study, participants were interviewed for migraine history in 1993–1995 and were followed for incident AF through 2013. AF was adjudicated using ECGs, discharge codes, and death certificates. Multivariable Cox proportional hazards models were used to study the relation between migraine and its subtypes with incident AF, compared with controls without headaches. Mediation analysis was conducted to test whether AF was a mediator of migraine with visual aura-associated stroke risk.ResultsOf 11,939 participants assessed for headache and without prior AF or stroke, 426 reported migraines with visual aura, 1,090 migraine without visual aura, 1,018 nonmigraine headache, and 9,405 no headache. Over a 20-year follow-up period, incident AF was noted in 232 (15%) of 1,516 with migraine and 1,623 (17%) of 9,405 without headache. After adjustment for multiple confounders, migraine with visual aura was associated with increased risk of AF compared to no headache (hazard ratio 1.30, 95% confidence interval 1.03–1.62) as well as when compared to migraine without visual aura (hazard ratio 1.39, 95% confidence interval 1.05–1.83). The data suggest that AF may be a potential mediator of migraine with visual aura–stroke risk.ConclusionsMigraine with aura was associated with increased risk of incident AF. This may potentially lead to ischemic strokes.

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Less dementia after catheter ablation for atrial fibrillation: a nationwide cohort study

European Heart Journal ◽

10.1093/eurheartj/ehaa726 ◽

2020 ◽

Vol 41 (47) ◽

pp. 4483-4493 ◽

Cited By ~ 1

Author(s):

Daehoon Kim ◽

Pil-Sung Yang ◽

Jung-Hoon Sung ◽

Eunsun Jang ◽

Hee Tae Yu ◽

...

Keyword(s):

Atrial Fibrillation ◽

Catheter Ablation ◽

Confidence Interval ◽

Medical Therapy ◽

Hazard Ratio ◽

Dementia Risk ◽

Increased Risk ◽

Ablation Success ◽

Korean National Health Insurance

Abstract Aims Accumulating evidence shows that atrial fibrillation (AF) is associated with an increased risk of dementia. Catheter ablation for AF prolongs the duration of sinus rhythm, thereby improving the quality of life. We investigated the association of catheter ablation for AF with the occurrence of dementia. Methods and results Using the Korean National Health Insurance Service database, among 194 928 adults with AF treated with ablation or medical therapy (antiarrhythmic or rate control drugs) between 1 January 2005 and 31 December 2015, we studied 9119 patients undergoing ablation and 17 978 patients managed with medical therapy. The time-at-risk was counted from the first medical therapy, and ablation was analysed as a time-varying exposure. Propensity score-matching was used to correct for differences between the groups. During a median follow-up of 52 months, compared with patients with medical therapy, ablated patients showed lower incidence and risk of overall dementia (8.1 and 5.6 per 1000 person-years, respectively; hazard ratio 0.73, 95% confidence interval 0.58–0.93). The associations between ablation and dementia risk were consistently observed after additionally censoring for incident stroke (hazard ratio 0.76, 95% confidence interval 0.61–0.95) and more pronounced in cases of ablation success whereas no significant differences observed in cases of ablation failure. Ablation was associated with lower risks of dementia subtypes including Alzheimer’s disease and vascular dementia. Conclusion In this nationwide cohort of AF patients treated with catheter ablation or medical therapy, ablation was associated with decreased dementia risk. This relationship was evident after censoring for stroke and adjusting for clinical confounders.

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Use of Antiasthmatic Drugs and the Risk of Type 1 Diabetes in Children: A Nationwide Case-Cohort Study

American Journal of Epidemiology ◽

10.1093/aje/kwaa002 ◽

2020 ◽

Vol 189 (8) ◽

pp. 779-787 ◽

Cited By ~ 1

Author(s):

Johanna Metsälä ◽

Annamari Lundqvist ◽

Lauri J Virta ◽

Minna Kaila ◽

Mika Gissler ◽

...

Keyword(s):

Type 1 Diabetes ◽

Cohort Study ◽

Confidence Interval ◽

Cox Regression ◽

Inhaled Corticosteroids ◽

Anatomical Therapeutic Chemical ◽

Hazard Ratio ◽

Increased Risk ◽

Reference Cohort

Abstract Asthma has been reported to be associated with an increased risk of type 1 diabetes mellitus in childhood, but the reasons are unclear. We examined whether the use of antiasthmatic drugs was associated with the development of type 1 diabetes in childhood in a nationwide, register-based case-cohort study. We identified all children who were born January 1, 1995, through December 31, 2008, in Finland and diagnosed with type 1 diabetes by 2010 (n = 3,342). A 10% random sample from each birth-year cohort was selected as a reference cohort (n = 80,909). Information on all dispensed antiasthmatic drugs (Anatomical Therapeutic Chemical classification system code R03) during 1995–2009 was obtained, and associations between the use of antiasthmatic drugs and the development of type 1 diabetes were investigated using time-dependent and time-sequential Cox regression models. Dispensed inhaled corticosteroids and inhaled β-agonists were associated with an increased risk of type 1 diabetes after adjusting for other antiasthmatic drugs, asthma, sex, and birth decade (hazard ratio = 1.29, 95% confidence interval: 1.09, 1.52, and hazard ratio = 1.22, 95% confidence interval: 1.07, 1.41, respectively). These findings suggest that children using inhaled corticosteroids or inhaled β-agonists might be at increased risk of type 1 diabetes.

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Abstract 2026: Atrial Fibrillation Predicts Ventricular Arrhythmogenicity In Heart Failure

Circulation ◽

10.1161/circ.116.suppl_16.ii_438-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Kristina Lemola ◽

Razi Khan ◽

Stanley Nattel ◽

Sakari Lemola ◽

Peter G Guerra ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Primary Prevention ◽

Cox Regression ◽

Left Ventricular ◽

Hazard Ratio ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Increased Risk ◽

N 93

Background: Atrial fibrillation (AF) is associated with appropriate ICD discharges in patients with primary prevention indications. We explored potential effect modifiers impacting on ventricular arrhythmogenic risk associated with AF. Methods and Results: A retrospective cohort study was conducted on 215 consecutive patients with ICDs for primary prevention having a left ventricular ejection fraction (LVEF) < <26>35% and followed for 1.3±0.7 years. Mean age was 61.0±0.7 years and 17% were women. Cox regression models were explored in subgroups of patients stratified by demographic parameters, prior medical and surgical history, physical exam features, laboratory findings, and results of diagnostic tests. Appropriate ICD discharges were received by 10% of patients. AF was associated with a 3.5 fold increased risk [95% CI (1,5, 8.1), P=0.005]. Effect modifiers for the relationship between AF and appropriate ICD discharges included QRS duration and QTc. In patients with a QRS>130 msec (N=93), 6 of 33 (18%) patients with AF received appropriate ICD discharges versus 2 of 60 (3%) without AF (P=0.03). In this subgroup, AF was associated with a hazard ratio of 5.1 (P=0.049). Among individuals with a QTc >440 msec (N=93), 6 of 32 (19%) AF patients received appropriate ICD discharges versus 1 of 61 (2%) without AF (P=0.01). AF was associated with a hazard ratio of 10.3 (P=0.031). Five of 28 patients (18%) with both prolonged QRS and QTc duration (N=77) that also having AF received appropriate ICD discharges compared to 0 of 49 of patients without AF (P=0.005). After adjusting for medical therapy, AF independently predicted appropriate ICD discharges in subgroups with and without QRS and QTc increase. Conclusion: AF portends increased risk for ventricular tachyarrhythmias in patients with heart failure, particularly when associated with conduction and/or repolarization abnormalities. This finding may reflect common depolarization and repolarization defects associated with the arrhythmic milieu contributing to AF and ventricular arrhythmias, or adverse consequences of AF on the complex neurohumoral/electrophysiological substrate underlying ventricular arrhythmogenesis in heart failure.

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Factors that contribute to urban–rural gradients in risk of schizophrenia: Comparing Danish and Western Australian registers

Australian & New Zealand Journal of Psychiatry ◽

10.1177/00048674211009615 ◽

2021 ◽

pp. 000486742110096

Author(s):

Oleguer Plana-Ripoll ◽

Patsy Di Prinzio ◽

John J McGrath ◽

Preben B Mortensen ◽

Vera A Morgan

Keyword(s):

Confidence Interval ◽

Western Australia ◽

Urban Areas ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Indigenous Status ◽

Increased Risk ◽

The Relationship ◽

Western Australian

Introduction: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that individuals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. Methods: We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia ( N = 428,784) and Denmark ( N = 1,357,874). Children were categorised according to the level of urbanicity of their mother’s residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. Results: During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). Discussion: Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.

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