Abstract We investigated associations between body mass index (BMI) in adolescence with development of aortic valve stenosis (AVS) in early adulthood, and clinical outcomes among those who develop AVS. We used data from 1 701 390 men (mean age, 18.3 ± 0.8 years) enrolled in compulsory conscription for military service in Sweden from 1969 to 2005. Anthropometrics, blood pressure, fitness, muscle strength and IQ were recorded at baseline. Over a median follow-up of 32 years (IQR, 24–41 years), 5766 men were diagnosed with AVS (mean age 54.7 ± 9.4 years). After multivariable adjustment, individuals with a BMI of < 18.5 kg/m2, compared to those with a low-normal BMI (20.0–<22.5 kg/m2) showed lower risk (HR 0.70; 95% CI 0.61–0.80) of AVS. Higher BMI categories were progressively associated with increased risk, reaching HR 1.91 (95% CI 1.12–3.25) for BMI 35–50 kg/m². Further on, those diagnosed with AVS were followed for a median of ~ 5.5 years. The multivariable-adjusted HR for all-cause mortality, cardiovascular mortality, and heart failure for obese (BMI 30–50 kg/m2), compared to BMI < 20.0 kg/m2 in men diagnosed with AVS, were 4.69 (95% CI 2.61–8.44), 4.09 (95% CI 1.72–9.73), and 2.76 (95% CI, 1.36–5.60), respectively. Higher BMI in youth, even within the conventional normal range, is associated with an elevated risk of developing AVS in early adulthood, whereas low BMI appears protective. Long-term exposure of obesity in individuals with AVS is associated with worse survival and higher risk of cardiovascular events.

The insulin-like growth factor (IGF) system has significance for poststroke outcomes. Previously, we reported that low serum IGF-II (s-IGF-II) in the acute phase is associated with poststroke mortality, and that IGF-II is lower among males. Given the known interactions of the IGF system and estrogen receptor signaling, s-IGF-II may have sex-specific effects. In this study, we conducted a secondary analysis of sex differences in s-IGF-II and poststroke functional outcomes and mortality after ischemic stroke (IS) in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS, males; n = 315, females; n = 177). Functional outcomes were assessed using the modified Rankin scale (mRS) at 3 months and 2 years poststroke. Survival was recorded for 7 years or until death. Males in the lowest quintile of acute s-IGF-II had a higher poststroke mortality, with a crude hazard ratio [HR] of 2.52 (95% confidence interval [CI]) 1.59-3.99) and an adjusted HR of 1.83 (95% CI 1.09-3.06). No corresponding significant association was observed in females. Although acute s-IGF-II was crudely associated with poor functional outcomes among males after 3 months and 2 years, these associations were not independent of initial stroke severity in adjusted models. In conclusion, low levels of acute s-IGF-II are linked with poststroke mortality among males, but not significantly in females. Further studies are, however, warranted with sex hormone analysis, consideration of specific cause of death, and more females.

Background: Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer’s disease (AD). Objective: To explore whether serum IGF-I is associated with magnetic resonance imaging – estimated brain white matter volumes or cognitive functions. Methods: In a prospective study of SCI/MCI (n = 106) and AD (n = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and Stroop tests I–III at baseline, and after 2 years. Results: IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables. Conclusions: Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain.

Background and aims: While there is increasing evidence for the short-term effectiveness of exercise interventions for adults with anxiety disorders, follow-up studies are rare. The aim of this study was to examine whether the significant reductions in anxiety and depression symptoms observed in connection with our primary care-based 12-week exercise RCT were maintained at subsequent follow-up after nine-months. A further aim was to investigate the hypothesis whether exercise interacted with antidepressant medication. Methods: 113 out of 153 who completed the 12-week intervention completed the follow-up assessments. Symptoms were self-assessed with the Beck Anxiety Index (BAI) and the Montgomery & Aring;sberg Depression Rating Scale (MADRS-S) at baseline, intervention completion (the 12-weeks follow-up) and 9 months post-intervention (the 1-year follow up). Results: The reduced symptoms of anxiety and depression effects seen after 12 weeks in the intervention groups were maintained at the 1-year follow-up. Similar reductions were seen in the control group. However, among antidepressant users, the odds ratios for the intervention group to reach improvement in anxiety were four-fold, and in depression, eleven-fold compared to controls at the 1-year follow-up. Conclusion: The results strengthen the view that physical exercise is an effective treatment for anxiety especially in among those with antidepressant treatment.

Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25–30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled “the obesity paradox”. Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5–25), overweight (25–30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3–6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30–4.14) and obese (OR 2.25, 95% CI 1.08–4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.

Background: Exercise interventions show promise in the treatment of anxiety disorders, but effects on healthrelated quality of life (HR-QoL), work ability, and sick leave are little studied. We investigated these outcomes in a 12-week randomized controlled trial with a 1-year follow-up. Methods: Patients aged 18-65 (n = 222) with anxiety disorders from primary care centers in Gothenburg were randomized to a control group or one of two 12-week exercise intervention groups (low-intensity, [LI] and moderate/high-intensity, [HI]); 148 were evaluated at 12-weeks and 113 completed the 1-year follow-up. The EuroQol 5D (EQ5D; index and the visual analogue scale [VAS]), work ability score (WAS), presenteeism, and selfreported sick leave were assessed at baseline, 12 weeks, and 1 year. Improvements were defined by binary cutoffs for each scale. Binary logistic regression with odds ratios (OR) and 95 % confidence intervals (CI) were reported. Results: There were improved scores for EQ5D and WAS in the HI group compared to controls after 12 weeks (EQ5D index: 4.74 [1.91-11.7], EQ5D-VAS 4.00, [1.65-9.72], WAS 3.41 [1.24-7.37]) and 1 year (EQ5D index: 3.05 [1.05-8.81], EQ5D-VAS 3.20 [1.16-8.84], WAS 5.50 [1.85-16.3]). Post-hoc analysis showed higher ORs in participants on antidepressants (n = 75) (12-week EQ5D index: OR 9.95 [2.85-34.8]) and significant improvements in EQ5D scores for both intervention groups after 1 year. There were no between-group differences for presenteeism or sick leave. Limitations: Discontinuation was high, mostly early after randomization (n = 74), as is common for anxiety interventions. Conclusions: HI Exercise improves HR-QoL and work ability in anxiety patients, especially when combined with antidepressants.

The beneficial effects of exercise are partly mediated via local or systemic functions of the insulin-like growth factor-1 (IGF-1) system. As IGF-1 increases local brain hemoglobin beta (Hbb) transcripts, we hypothesized that exercise could have similar effects. Mice were single-housed with free access to running wheels for seven days. After sacrifice and saline perfusion, the expression of 13 genes was quantified using real-time quantitative polymerase chain reaction (RT-qPCR) in three brain regions: the prefrontal cortex, motor cortex, and hippocampus. In addition, plasma insulin, glucose, homeostatic model assessment of IR (HOMA-IR), C-peptide, and IGF-1 were investigated. We show that hemoglobin-related transcripts (Hbb and 5'-aminolevulinate synthase 2 [Alas2]) increased 46-63% in the running group, while IGF-1-related genes [Igf1 / growth hormone receptor (Ghr)] decreased slightly (7%). There were also moderate to large correlations between Hbb- and IGF-1-related genes in the running group but not in the sedentary group. HOMA-IR, plasma glucose, and insulin changed marginally and non-significantly, but there was a trend toward an increase in plasma-IGF-1 in the running group. In conclusion, seven days of running increased Hbb-related transcripts in three brain regions. Hbb-related transcripts correlated with components of the brain IGF-1 system only in the running group.

Background Coronary heart disease remains the dominant cause of death worldwide. To improve cardiovascular disease prevention, knowledge of early key risk factors, especially those that are modifiable, is essential. The ongoing global obesity epidemic is of particular concern. We aimed to determine whether body mass index at conscription predicts early acute coronary events among men in Sweden. Methods and Results This was a population-based Swedish cohort study of conscripts (n=1 668 921; mean age, 18.3 years; 1968-2005), with follow-up through linkage to the nationwide Swedish patient and death registries. Risk of a first acute coronary event (hospitalization for acute myocardial infarction or coronary death) during follow-up (1-48 years) was calculated with generalized additive models. Objective baseline measures of fitness and cognition were included in the models in secondary analyses. During follow-up, there were 51 779 acute coronary events, of which 6457 (12.5%) were fatal within 30 days. Compared with men at the lowest end of the normal body mass index spectrum (body mass index, 18.5 kg/m2), an increasing risk for a first acute coronary event was observed, with hazard ratios (HRs) peaking at 40 years of age. After multivariable adjustments, men with a body mass index of 35 kg/m2 had an HR of 4.84 (95% CI, 4.29-5.46) for an event before the age of 40 years. Conclusions An increased risk of an early acute coronary event was detectable within normal levels of body weight at the age of 18 years, increasing to almost 5-fold in the highest weight category at 40 years of age. Given increasing levels of body weight and prevalence of overweight and obesity in young adults, the current decrease in coronary heart disease incidence in Sweden may flatten or even reverse in the near future.

IntroductionComprehensive studies mapping domain-specific trajectories of recovery after stroke and biomarkers reflecting these processes are scarce. We, therefore, initiated an exploratory prospective observational study of stroke cases with repeated evaluation, theFIND Stroke Recovery Study. We aim to capture trajectories of recovery from different impairments, including cognition, in combination with broad profiling of blood and imaging biomarkers of the recovery.Methods and analysisWe recruit individuals with first-ever stroke at the stroke unit at the Sahlgrenska University Hospital, Sweden, to FIND. The inclusion started early 2018 and we aim to enrol minimum 500 patients. Neurological and cognitive impairments across multiple domains are assessed using validated clinical assessment methods, advanced neuroimaging is performed and blood samples for biomarker measuring (protein, RNA and DNA) at inclusion and follow-up visits at 3 months, 6 months, 1 year, 2 years and 5 years poststroke. At baseline and at each follow-up visit, we also register clinical variables known to influence outcomes such as prestroke functioning, stroke severity, acute interventions, rehabilitation, other treatments, socioeconomic status, infections (including COVID-19) and other comorbidities. Recurrent stroke and other major vascular events are identified continuously in national registers.Ethics and disseminationFIND composes a unique stroke cohort with detailed phenotyping, repetitive assessments of outcomes across multiple neurological and cognitive domains and patient-reported outcomes as well as blood and imaging biomarker profiling. Ethical approval for the FIND study has been obtained from the Regional Ethics Review Board in Gothenburg and the Swedish Ethics Review Board. The results of this exploratory study will provide novel data on the time course of recovery and biomarkers after stroke. The description of this protocol will inform the stroke research community of our ongoing study and facilitate comparisons with other data sets.Trial registration numberThe protocol is registered athttp://www.clinicaltrials.gov, Study ID:NCT05708807.

BACKGROUND:The work of healthcare professionals (HCPs) in the emergency department (ED) involves effective communication and efficient teamwork, which may be perceived differently by patients and HCPs. Therefore, it is important to explore patient perspectives of information exchange and clinical assessment.AIM:To evaluate experiences of care, communication, and teamwork from ED patients' perspectives.METHODS:Semi-structured interviews were conducted with 17 patients who were assessed in a Swedish ED during Spring 2021. Thematic analysis was used.RESULTS:Participants' experiences reflected the complex environment of the ED. Findings emphasize the importance of information exchange in relation to a caring approach. Three themes emerged: the need for a caring approach by HCPs towards patients'; the need for dialogue between patient and HCPs; and the need for information on ED environment constraints.CONCLUSIONS:Patients felt comforted when they experienced a caring empathic approach from the HCPs. For example, patients valued an individual holistic approach rather than feeling that they were being objectified by their medical conditions. This was important in coping with the anxiety caused by a stressful ED environment. There is a critical need for effective exchange of information between patients and HCPs.

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4-8.5 and OR 5.7, 95% CI: 2.5-12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1-3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.

Haemoglobin beta (Hbb) and delta-aminolevulinate synthase 2 (Alas2) messenger RNA (mRNA) is mainly found in immature red blood cells, reticulocytes, and not in mature erythrocytes. However, these are also expressed in other tissues such as brain cells, mostly neurons. Therefore, exact quantification of neural tissue homogenates may be confounded by remaining blood in the brain vasculature that may give falsely high values of Hbb/Alas2 expression. To investigate and compare the contribution of local Hbb/Alas2 expression, we investigated mRNA expression locally in the hippocampus and prefrontal cortex, in post-sacrifice saline-perfused and non-perfused mice and rats. Although there was a higher level of Hbb/Alas2 transcripts in the non-perfused animals, there was a significant mRNA expression in perfused brains that could at most partially be explained by remaining blood. Finally, we suggest that saline-perfusion should be recommended for quantification of brain Hbb/Alas2 transcripts in homogenates.

Background: There is a need for high-quality research regarding exercise interventions for persons with anxiety disorders. We investigate whether a 12-week exercise intervention, with different intensities, could reduce anxiety symptoms in patients with anxiety disorders. Methods: 286 patients were recruited from primary care in Sweden. Severity of symptoms was self-assessed using the Beck Anxiety Inventory (BAI) and the Montgomery Asberg Depression Rating Scale (MADRS-S). Participants were randomly assigned to one of two group exercise programs with cardiorespiratory and resistance training and one control/standard treatment non-exercise group, with 1:1:1 allocation. Results: Patients in both exercise groups showed larger improvements in both anxiety and depressive symptoms compared to the control group. No differences in effect sizes were found between the two groups. To study a clinically relevant improvement, BAI and MADRS-S were dichotomized with the mean change in the control group as reference. In adjusted models the odds ratio for improved symptoms of anxiety after low-intensity training was 3.62 (CI 1.34-9.76) and after moderate/high intensity 4.88 (CI 1.66-14.39), for depressive symptoms 4.96 (CI 1.81-13.6) and 4.36 (CI 1.57-12.08) respectively. There was a significant intensity trend for improvement in anxiety symptoms. Limitations: The use of self-rating measures which bears the risk of an under- or overestimation of symptoms. Conclusions: A 12-week group exercise program proved effective for patients with anxiety syndromes in primary care. These findings strengthen the view of physical exercise as an effective treatment and could be more frequently made available in clinical practice for persons with anxiety issues.

Introduction The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence. Methods and analysis This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified. Ethics and dissemination This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals.

Aims:We have shown that growth hormone (GH) treatment poststroke increases neuroplasticity in peri-infarct areas and the hippocampus, improving motor and cognitive outcomes. We aimed to explore the mechanisms of GH treatment by investigating how GH modulates pathways known to induce neuroplasticity, focusing on association between brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in the peri-infarct area, hippocampus, and thalamus.Methods:Recombinant human growth hormone (r-hGH) or saline was delivered (0.25 μl/hr, 0.04 mg/day) to mice for 28 days, commencing 48 hours after photothrombotic stroke. Protein levels of pro-BDNF, total-mTOR, phosphorylated-mTOR, total-p70S6K, and phosporylated-p70S6K within the peri-infarct area, hippocampus, and thalamus were evaluated by western blotting at 30 days poststroke.Results:r-hGH treatment significantly increased pro-BDNF in peri-infarct area, hippocampus, and thalamus (p < 0.01). r-hGH treatment significantly increased expression levels of total-mTOR in the peri-infarct area and thalamus (p < 0.05). r-hGH treatment significantly increased expression of total-p70S6K in the hippocampus (p < 0.05).Conclusion:r-hGH increases pro-BDNF within the peri-infarct area and regions that are known to experience secondary neurodegeneration after stroke. Upregulation of total-mTOR protein expression in the peri-infarct and thalamus suggests that this might be a pathway that is involved in the neurorestorative effects previously reported in these animals and warrants further investigation. These findings suggest region-specific mechanisms of action of GH treatment and provide further understanding for how GH treatment promotes neurorestorative effects after stroke.

Background Interprofessional teams contribute to patient safety during clinical care. However, little is known about how interprofessional teams manage and cope with critical incidents in the emergency department (ED). Therefore, the study aimed to describe healthcare professionals (HCPs) perceptions of critical incidents linked to the enablers of and barriers to interprofessional teamwork in a high-risk setting, the ED. Methods Individual interviews with HCPs regarding events at the ED were held during the period of May 2019–January 2020. The Critical Incident Technique approach was used to guide the interviews and the qualitative analysis. Data were analyzed inductively using qualitative content analysis. Results Interview participants (n = 28) included 7 physicians (25%), 12 registered nurses (43%), 7 nurse assistants (25%) and 2 administrators (7%). Overall, 108 critical incidents were described. Eight categories that described functional and dysfunctional experiences within interprofessional teamwork were identified: salience of reflection; professional experience makes a difference; demanding physical and psychosocial work environment; balancing communication demands; lacking management support, structure, and planning; tensions between professional role and responsibility; different views on interprofessional teamwork; and confidence in interprofessional team members. Conclusion Findings of this study indicate that poor ED-specific communication and limited professional experience are essential factors in handling critical incidents related to interprofessional teamwork. An important aspect of critical incident management is the ergonomics of the physical work environment and how it enables interprofessional teamwork. This study emphasizes the factors enabling interprofessional teamwork to manage critical incidents in the complex working environment of the ED.

Abstract Background To improve cardiovascular disease prevention, knowledge of early key risk factors for aortic disease (AD), especially those that are modifiable such as overweight and obesity, is essential. Therefore, we aimed to determine whether measures of body size, including body mass index (BMI), body surface area (BSA) and body height in adolescent men is associated to AD later in life. Methods Register-based cohort study of conscripts (n=1,575,909; mean age at baseline, 18.3 years) who enlisted during 1968–2005 in Sweden. Follow-up was done through linkage to the nationwide Swedish inpatient- and cause of death registries. Risk of AD (hospitalization for Aortic aneurysm or aortic dissection) during follow-up (5–48 years) was calculated with cox proportional hazard models. Results During follow-up there were 8185 cases of AD. Incidence rates (per 100000 person years) increased with increasing body size measures; BSA 14.19 (95% CI, 13.6–14.8) for Q1 vs 19.36 (18.6–20.2) for Q4; BMI 15.89 (15.2–16.6) for Q1 vs. 16.89 (16.2–17.6) for Q4; and body height 13.45 (95% CI, 12.9–14.1) for Q1 vs 19.93 (95% CI, 19.1–20.8) for Q4. Compared to the lowest, the highest quartile of BSA and body height was associated with increased risk of AD (adjusted HR (aHR) 1.95 (95% confidence interval 1.83–2.08) and 1.72 (1.62–1.83) respectively). For BMI, the corresponding aHR was 1.40 (1.31–1.49, Figure 1). Conclusion Large body size in early adulthood is associated with risk for aortic disease later in life. The pathophysiological mechanisms remain uncertain and warrants further investigation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Swedish state under the agreement concerning research and education of doctors [grant number ALFGBG-427301]; the Swedish Society for Physicians, the Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, Sweden, and the Swedish Heart and Lung Foundation [grant number 2015-0438]; the Swedish Research Council [grant numbers 2013-5187 (SIMSAM), 2013-4236]; and the Swedish Council for Health, Working Life and Welfare (FORTE) [grant numbers 2013-0325]

Background We sought to determine the role of obesity in adolescent men on development of atrial fibrillation (AF) and subsequent associated clinical outcomes in subjects diagnosed with AF. Methods and Results We conducted a nationwide, register‐based, cohort study of 1 704 467 men (mean age, 18.3±0.75 years) enrolled in compulsory military service in Sweden from 1969 through 2005. Height and weight, blood pressure, fitness, muscle strength, intelligence quotient, and medical disorders were recorded at baseline. Records obtained from the National Inpatient Registry and the Cause of Death Register were used to determine incidence and clinical outcomes of AF. During a median follow‐up of 32 years (interquartile range, 24–41 years), 36 693 cases (mean age at diagnosis, 52.4±10.6 years) of AF were recorded. The multivariable‐adjusted hazard ratio (HR) for AF increased from 1.06 (95% CI, 1.03–1.10) in individuals with body mass index (BMI) of 20.0 to <22.5 kg/m2 to 3.72 (95% CI, 2.44–5.66) among men with BMI of 40.0 to 50.0 kg/m2, compared with those with BMI of 18.5 to <20.0 kg/m2. During a median follow‐up of ≈6 years in patients diagnosed with AF, we identified 3767 deaths, 3251 cases of incident heart failure, and 921 cases of ischemic stroke. The multivariable‐adjusted HRs for all‐cause mortality, incident heart failure, and ischemic stroke in AF‐diagnosed men with baseline BMI >30 kg/m2 compared with those with BMI <20 kg/m2 were 2.86 (95% CI, 2.30–3.56), 3.42 (95% CI, 2.50–4.68), and 2.34 (95% CI, 1.52–3.61), respectively. Conclusions Increasing BMI in adolescent men is strongly associated with early AF, and with subsequent worse clinical outcomes in those diagnosed with AF with respect to all‐cause mortality, incident heart failure, and ischemic stroke.