Exercise and health-related quality of life and work-related outcomes in primary care patients with anxiety disorders - A randomized controlled study.

BACKGROUND: Exercise interventions show promise in the treatment of anxiety disorders, but effects on health-related 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 self-reported sick leave were assessed at baseline, 12 weeks, and 1 year. Improvements were defined by binary cut-offs 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.

Occupation-specific risk estimates for suicide and non-fatal self-harm from a Swedish cohort of male construction workers followed 1987-2018.

OBJECTIVES: While suicidal behaviour has become less prevalent in non-manual workers in recent decades, rates have increased in manual workers. We aimed to identify occupations within the construction industry with excess risk of suicide and non-fatal self-harm. METHODS: This cohort of Swedish construction workers comprises 389 132 individuals examined 1971-1993 and followed 1987-2018 using national hospital and cause of death registers. More than 200 job titles were merged into 22 occupational groups. For 296 891 men alive in 1987 and active in the construction sector, survival was calculated from baseline to first event of non-fatal self-harm or suicide and censored for emigration, long-term unemployment, disability pension, retirement, death from other causes or end of follow-up. HRs with 95% CIs were obtained from multiple Cox proportional hazard regression. RESULTS: Overall, 1618 cases of suicide and 4774 events of non-fatal self-harm were registered. Self-harm before baseline was the single largest risk factor for suicide, HR 9.3 (95% CI 7.5 to 11.6). Compared with the overall mean, labourers and rock workers had excess risk for suicide, HR 1.4 (95% CI 1.1 to 1.7) and 1.5 (95% CI 1.0 to 2.3), respectively, while electricians, clerks and foremen had reduced risk. Labourers, concrete workers, sheet metal workers, painters, glaziers and the group 'other construction workers' were at increased risk for non-fatal self-harm. Almost all categories of manual workers were at increased risk for suicidal behaviour relative to clerks and foremen. CONCLUSIONS: Specific occupations within the construction sector were associated with excess risk for suicidal behaviour. Future studies should identify underlying risk factors to inform tailored interventions.

Body mass index and fitness in late adolescence and risk of cardiovascular disease, respiratory disease, and overall death after COVID-19.

Objective: Since obesity and poor fitness appear to be unfavorable for both cardiovascular health and coping with viral infections such as COVID-19, they are of specific interest in light of the increased risk of cardiovascular and respiratory events now seen after infection with SARS-CoV-2. Therefore, the aim of the present study was to investigate how body mass index (BMI) and cardiorespiratory fitness (CRF) in late adolescence are associated with the risk of cardiovascular disease (CVD), respiratory disease, and mortality after COVID-19. Methods: In this study, 1.5 million 18-year-old Swedish men with BMI and CRF measured during enlistment for military service 1968-2005 were included. Hospitalized and non-hospitalized COVID-19 cases were identified through the Patient Register or positive polymerase chain reaction tests, and age-matched with non-infected controls. CVD, respiratory disease, and mortality after COVID-19 were divided into <60days, 60-180days, >180days post-infection. Cox regression models were used. Results: Hospitalized COVID-19 cases (n = 9839), compared to controls, had >10-fold, 50 to 70-fold, and >70-fold hazards of CVD, respiratory disease, and mortality over the initial 60 days post-infection with little variation across BMI or CRF categories. The elevated risks persisted at declining levels >180 days. For non-hospitalized COVID-19 cases (n = 181,822), there was a 4- to 7-fold increased acute mortality risk, and high CRF was associated with lower risk of post-infectious respiratory disease. Conclusions: The high hazards of adverse outcomes during the first two months after COVID-19 hospitalization, and across BMI and CRF categories, declined rapidly but were still elevated after six months. Adolescent CRF was associated with respiratory disease after COVID-19 without hospitalization, which gives further support to the health benefits of physical activity.

Psychosocial job stressors and risk of suicidal behavior - an observational study among Swedish men.

OBJECTIVE: This study aimed to explore the relationship between psychosocial job stressors and suicidal behavior (fatal and non-fatal) among Swedish men while controlling for potential confounders. METHODS: Population-based Swedish longitudinal cohort study of male conscripts without previous self-harm (N=1 483 310) enlisting 1968-2002. Conscription examinations included measures of IQ, stress resilience and psychiatric diagnoses. Job demand-control (JDC) exposure was assessed using the Swedish Job Exposure Matrix linked to specific occupations. Suicidal behavior among men aged 30-64 was identified in the National Hospital Register (non-fatal self-harm) and Swedish Cause of Death Register (suicide) during follow-up 2002-2014. Cox regression models were used to estimate associations between JDC category and suicidal behavior. RESULTS: In fully adjusted models, passive jobs (low demand-low control) showed the highest risk of suicidal behavior [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.25-1.43] compared to those with low strain (low demand-high control), followed by high strain (high demand-low control) (HR 1.12, 95% Cl 1.03-1.22). A lower risk of suicidal behavior was found in the active category, where levels of both demand and control are high (HR 0.64, 95% Cl 0.60-0.70). Separate analyses for suicide as outcome revealed a lower risk of suicide in persons with active jobs (high demands-high control). The passive category showed a higher risk for suicide, but the association did not remain after adjustment for stress resilience and IQ. CONCLUSIONS: These results show that psychosocial job stressors among men are associated with risk for suicidal behavior. Improving job control has the potential to decrease suicidal behavior for this group.

Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries.

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.

Effects of exercise on symptoms of anxiety in primary care patients: A randomized controlled trial.

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 Åsberg 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.

Anxiety severity and cognitive function in primary care patients with anxiety disorder: a cross-sectional study.

BACKGROUND: Deficits in cognitive performance are reported in patients with anxiety disorders, but research is limited and inconsistent. We aimed to investigate cross-sectional associations between cognitive function, with focus on executive function, and anxiety severity in primary care patients diagnosed with anxiety disorders. METHODS: 189 Swedish patients aged 18-65 years (31% men) with anxiety disorders diagnosed according to Mini International Neuropsychiatric Interview were included. Severity of anxiety was assessed using Beck Anxiety Inventory self-assessment scale. Digit span, block design and matrix reasoning tests from the Wechsler Adult Intelligence Scale IV, and the design fluency test from the Delis-Kaplan Executive Function System were used. Multivariable linear regression models were applied to investigate the relationship of anxiety severity and cognitive functioning. Comparisons were also performed to a normed non-clinical population, using the Wilcoxon signed rank test. RESULTS: More severe anxiety was associated with lower digit span test scores (R2 = 0.109, B = -0.040, p = 0.018), but not with block design, matrix reasoning or design fluency tests scores, after adjustment for comorbid major depression in a multivariable model. When compared to a normed population, patients with anxiety performed significantly lower on the block design, digit span forward, digit span sequencing and matrix reasoning tests. CONCLUSIONS: Severity of anxiety among patients with anxiety disorder was associated with executive functions related to working memory, independently of comorbid major depression, but not with lower fluid intelligence. A further understanding of the executive behavioral control in patients with anxiety could allow for more tailored treatment strategies including medication, therapy and interventions targeted to improve specific cognitive domains.

Global Prevalence of Young-Onset Dementia: A Systematic Review and Meta-analysis.

Importance: Reliable prevalence estimates are lacking for young-onset dementia (YOD), in which symptoms of dementia start before the age of 65 years. Such estimates are needed for policy makers to organize appropriate health care. Objective: To determine the global prevalence of YOD. Data Sources: The PubMed, Embase, CINAHL, and PsycInfo databases were systematically searched for population-based studies on the prevalence of YOD published between January 1, 1990, and March 31, 2020. Study Selection: Studies containing data on the prevalence of dementia in individuals younger than 65 years were screened by 2 researchers for inclusion in a systematic review and meta-analysis. Data Extraction and Synthesis: Prevalence estimates on 5-year age bands, from 30 to 34 years to 60 to 64 years, were extracted. Random-effects meta-analyses were conducted to pool prevalence estimates. Results were age standardized for the World Standard Population. Heterogeneity was assessed by subgroup analyses for sex, dementia subtype, study design, and economic status based on the World Bank classification and by meta-regression. Main Outcomes and Measures: Prevalence estimates of YOD for 5-year age bands. Results: A total of 95 unique studies were included in this systematic review, of which 74 with 2 760 379 unique patients were also included in 5-year age band meta-analyses. Studies were mostly conducted in Europe and in older groups in Asia, North America, and Oceania. Age-standardized prevalence estimates increased from 1.1 per 100 000 population in the group aged 30 to 34 years to 77.4 per 100 000 population in the group aged 60 to 64 years. This gives an overall global age-standardized prevalence of 119.0 per 100 000 population in the age range of 30 to 64 years, corresponding to 3.9 million people aged 30 to 64 years living with YOD in the world. Subgroup analyses showed prevalence between men and women to be similar (crude estimates for men, 216.5 per 100 000 population; for women, 293.1 per 100 000 population), whereas prevalence was lower in high-income countries (crude estimate, 663.9 per 100 000 population) compared with upper-middle-income (crude estimate, 1873.6 per 100 000 population) and lower-middle-income (crude estimate, 764.2 per 100 000 population) countries. Meta-regression showed that age range (P < .001), sample size (P < .001), and study methodology (P = .02) significantly influenced heterogeneity between studies. Conclusions and Relevance: This systematic review and meta-analysis found an age-standardized prevalence of YOD of 119.0 per 100 000 population, although estimates of the prevalence in low-income countries and younger age ranges remain scarce. These results should help policy makers organize sufficient health care for this subgroup of individuals with dementia. Study Registration: PROSPERO CRD42019119288.

Fitness, strength and severity of COVID-19: a prospective register study of 1 559 187 Swedish conscripts.

OBJECTIVE: To investigate the possible connection between cardiorespiratory fitness (CRF) and muscle strength in early adulthood and severity of COVID-19 later in life. DESIGN: Prospective registry-based cohort study. PARTICIPANTS: 1 559 187 Swedish men, undergoing military conscription between 1968 and 2005 at a mean age of 18.3 (SD 0.73) years. MAIN OUTCOME MEASURES: Hospitalisation, intensive care or death due to COVID-19 from March to September 2020, in relation to CRF and muscle strength. RESULTS: High CRF in late adolescence and early adulthood had a protective association with severe COVID-19 later in life with OR (95% CI) 0.76 (0.67 to 0.85) for hospitalisation (n=2 006), 0.61 (0.48 to 0.78) for intensive care (n=445) and 0.56 (0.37 to 0.85) for mortality (n=149), compared with the lowest category of CRF. The association remains unchanged when controlled for body mass index (BMI), blood pressure, chronic diseases and parental education level at baseline, and incident cardiovascular disease before 2020. Moreover, lower muscle strength in late adolescence showed a linear association with a higher risk of all three outcomes when controlled for BMI and height. CONCLUSIONS: Physical fitness at a young age is associated with severity of COVID-19 many years later. This underscores the necessity to increase the general physical fitness of the population to offer protection against future viral pandemics.

Late-adolescent risk factors for suicide and self-harm in middle-aged men: explorative prospective population-based study.

BACKGROUND: Recent reports show alarmingly high rates of suicide in middle-aged men, yet there are few long-term prospective studies that focus on suicidal behaviour in men in this age group. AIMS: To prospectively explore associations of potential risk factors at age 18 with suicide and self-harm in middle-aged men. METHOD: A population-based Swedish longitudinal cohort study of male conscripts with no history of self-harm at enlistment in 1968-1989 (n = 987 583). Conscription examinations included measures of cognitive performance, stress resilience, psychiatric diagnoses, body mass index (BMI), cardiovascular fitness and muscle strength. Suicides and self-harm at age 45-65 years were identified in the National Hospital Register and Swedish Cause of Death Register. Risks were calculated using Cox proportional hazards models. RESULTS: Low stress resilience (cause-specific hazard ratio CHR = 2.31, 95% CI 1.95-2.74), low cognitive ability (CHR = 2.01, 95% CI 1.71-2.37) as well as psychiatric disorders and low cardiovascular fitness in late adolescence were associated with increased risk for suicide in middle-aged men. Similar risk estimates were obtained for self-harm. In addition, high and low BMI as well as low muscle strength were associated with increased risk of self-harm. Associations also remained significant after exclusion of men with self-harm before age 45. CONCLUSIONS: This prospective study provides life-course perspective support that psychological and physical characteristics in late adolescence may have long-lasting consequences for suicidal behaviour in middle-aged men, a very large population at heightened risk of suicide.

Cardiovascular fitness and risk of migraine: a large, prospective population-based study of Swedish young adult men.

OBJECTIVES: To examine the longitudinal relationship between cardiovascular fitness in young adult men and future risk of migraine and to estimate eventual differential effects among categories of body mass index (BMI) and blood pressure. DESIGN: National, prospective, population-based cohort study. SETTING: Sweden 1968-2014. PARTICIPANTS: 18-year-old Swedish men (n=1 819 828) who underwent mandatory military conscription examinations during the years 1968-2005. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was the first dispensation of prescribed migraine-specific medication, identified using the Swedish Prescribed Drug Register. The secondary outcome was documented migraine diagnosis from the Swedish National Hospital Register. RESULTS: During follow-up, 22 533 men filled a prescription for migraine-specific medication. After confounding adjustment, compared with high cardiovascular fitness, low and medium fitness increased the risk of migraine-specific medication (risk ratio (RR)low: 1.29, 95% CI 1.24 to 1.35; population attributable fraction: 3.6%, 95% CI 1.7% to 5.3% and RRmedium: 1.15, 95% CI 1.12 to 1.19; population attributable fraction: 8.0%, 95% CI 4.0% to 11.7%). To assess potential effect measure modification, stratified analyses of these association by levels of BMI and blood pressure showed that lower fitness levels increased risk of migraine across all groups except among underweight men or men with high diastolic blood pressure. CONCLUSIONS: Young men with a lower cardiovascular fitness had a higher long-term risk of developing pharmacological prescription-requiring migraine. This study contributes with information regarding risk factors for migraine in men, an understudied population in migraine research.

Effects of exercise on symptoms of anxiety, cognitive ability and sick leave in patients with anxiety disorders in primary care: study protocol for PHYSBI, a randomized controlled trial.

BACKGROUND: Anxiety disorders are common and associated with reduced quality of life, impaired physical and mental health and an increased economic burden for society. While evidence exists for the effectiveness of exercise treatment for depression, there is a need for high-quality randomized clinical trials (RCT) with a focus on anxiety disorders. Further research is also warranted regarding outcomes of cognitive function, other health-related variables, dose-response effects, work ability and potential mechanisms. METHOD/DESIGN: Using a parallel, RCT design with three assessment points (baseline, post-intervention and one-year follow-up), we aim to assess the effect of a 12-week exercise intervention in primary care patients with anxiety disorders (n = 180), diagnosed using the Mini International Neuropsychiatric Interview (M.I.N.I; Swedish version 6.0.0d DSM-IV). Participants are randomly assigned to three physical exercise groups: one low-intensity training group, one moderate- to high intensity training group and one control non-exercise group. Assessments include measures of anxiety symptoms, cognitive function, physical health variables such as cardiovascular fitness, sick-leave and levels of hormones/cytokines in blood samples. DISCUSSION: Findings from this study will provide novel insights regarding the effects of exercise treatment on not only anxiety symptoms but also other outcomes including mental and physical health, cognitive function, dose-response effects, work ability/sick leave and on biomarkers that may help explain underlying mechanisms. TRIAL REGISTRATION: The trial was registered at ClinicalTrial.gov NCT03247270 August 8, 2017.

Cause-specific mortality in Swedish males diagnosed with non-psychotic mental disorders in late adolescence: a prospective population-based study.

BACKGROUND: While risk of premature death is most pronounced among persons with severe mental illness, also milder conditions are associated with increased all-cause mortality. We examined non-psychotic mental (NPM) disorders and specific causes of natural death in a cohort of late adolescent men followed for up to 46 years. METHODS: Prospective cohort study of Swedish males (n=1 784 626) who took part in structured conscription interviews 1968-2005. 74 525 men were diagnosed with NPM disorders at or prior to conscription. Median follow-up time was 26 years. HRs for cause-specific mortality were calculated using Cox proportional hazards models. RESULTS: Risks in fully adjusted models were particularly elevated for death by infectious diseases (depressive and neurotic/adjustment disorders (HR 2.07; 95% CI 1.60 to 2.67), personality disorders (HR 2.90; 95% CI 1.96 to 4.28) and alcohol-related and other substance use disorders (HR 9.02; 95% CI 6.63 to 12.27)) as well as by gastrointestinal causes (depressive and neurotic/adjustment disorders (HR 1.64; 95% CI 1.42 to 1.89), personality disorders (HR 2.77; 95% CI 2.27 to 3.38) and alcohol-related/substance use disorders (HR 4.41; 95% CI 3.59 to 5.42)). CONCLUSION: Young men diagnosed with NPM disorders had a long-term increased mortality risk, in particular due to infectious and gastrointestinal conditions. These findings highlight the importance of early preventive actions for adolescents with mental illness.

Risk factors in Swedish young men for amyotrophic lateral sclerosis in adulthood.

Recent research suggests that the incidence of amyotrophic lateral sclerosis (ALS) may be on the rise. Since ALS becomes predominant in later life, most studies on causal factors are conducted in middle-aged or older populations where potentially important influences from early life can usually not be adequately captured. We aimed to investigate predictors in young Swedish men for ALS in adulthood. Therefore, we performed a prospective cohort study of young men (aged 16-25, n = 1,819,817) who enlisted 1968-2005 and took part in comprehensive conscription examinations. Incident cases of ALS (n = 526) during up to 46 years of follow-up were identified in the National Hospital Register and Swedish Cause of Death Register. Those who developed ALS had lower BMI (body mass index) at conscription than their peers (p = 0.03). The risk of ALS during follow-up was calculated with Cox proportional hazards models. No associations were found with physical fitness, erythrocyte sedimentation rate, or non-psychotic mental disorders. Low overall muscle strength compared to high overall muscle strength [hazard ratio (HR) 1.36; 95% confidence interval (CI) 1.01-1.83] and low BMI (a one-unit increase HR 0.96; 95% CI 0.93-0.99) and lower erythrocyte volume fraction (a one-unit increase HR 0.96; 95% CI 0.92-0.998) were the statistically significant predictors for ALS in adjusted models. These findings provide novel epidemiologic evidence of a prospective association between low overall muscle strength and erythrocyte volume fraction in young men and ALS risk.

Nonpsychotic Mental Disorders in Teenage Males and Risk of Early Stroke: A Population-Based Study.

BACKGROUND AND PURPOSE: Although the incidence of stroke is on the decline worldwide, this is not the case for early stroke. We aimed to determine whether nonpsychotic mental disorder at the age of 18 years is a risk factor for early stroke, and if adolescent cardiovascular fitness and intelligence quotient might attenuate the risk. METHOD: Population-based Swedish cohort study of conscripts (n=1 163 845) who enlisted during 1968 to 2005. At conscription, 45 064 males were diagnosed with nonpsychotic mental disorder. Risk of stroke during follow-up (5-42 years) was calculated with Cox proportional hazards models. Objective baseline measures of fitness and cognition were included in the models in a second set of analyses. RESULTS: There were 7770 first-time stroke events. In adjusted models, increased risk for stroke was observed in men diagnosed with depressive/neurotic disorders (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.11-1.37), personality disorders (HR, 1.52; 95% CI, 1.29-1.78), and alcohol/substance use disorders (HR, 1.61; 95% CI, 1.41-1.83) at conscription. Corresponding figures for fatal stroke were HR, 1.38; 95% CI, 1.06 to 1.79; HR, 2.26; 95% CI, 1.60 to 3.19; and HR, 2.20; 95% CI, 1.63 to 2.96. HRs for stroke were attenuated when fitness level and intelligence quotient were introduced. Associations remained significant for personality disorders and alcohol/substance use in the fully adjusted models. The interaction term was statistically significant for fitness but not for intelligence quotient. CONCLUSIONS: Our findings suggest that fitness may modify associations between nonpsychotic disorders and stroke. It remains to be clarified whether interventions designed to improve fitness in mentally ill youth can influence future risk of early stroke.

Influence of Cardiovascular Fitness and Muscle Strength in Early Adulthood on Long-Term Risk of Stroke in Swedish Men.

BACKGROUND AND PURPOSE: Low cardiovascular fitness (fitness) in mid- and late life is a risk factor for stroke. However, the respective effects on long-term stroke risk of fitness and muscle strength in early adulthood are unknown. Therefore, we analyzed these in a large cohort of young men. METHOD: We performed a population-based longitudinal cohort study of Swedish male conscripts registered in 1968 to 2005. Data on fitness (by the cycle ergometric test; n=1 166 035) and muscle strength (n=1,563,750) were trichotomized (low, medium, and high). During a 42-year follow-up, risk of stroke (subarachnoidal hemorrhage, intracerebral hemorrhage, and ischemic stroke) and fatality were calculated with Cox proportional hazards models. To identify cases, we used the International Classification of Diseases-Eighth to Tenth Revision in the Hospital Discharge Register and the Cause of Death Register. RESULTS: First-time stroke events were identified (subarachnoidal hemorrhage, n=895; intracerebral hemorrhage, n=2904; ischemic stroke, n=7767). For all stroke and fatality analysis any type of first-time stroke was recorded (n=10,917). There were inverse relationships in a dose-response fashion between fitness and muscle strength with any stroke (adjusted hazard ratios for the lowest, compared with the highest, tertile of each 1.70 [1.50-1.93] and 1.39 [1.27-1.53], respectively). There were stronger associations for fatal stroke. All 3 stroke types displayed similar associations. Associations between fitness and stroke remained when adjusted for muscle strength, whereas associations between muscle strength and stroke weakened/disappeared when adjusted for fitness. CONCLUSIONS: At the age of 18 years, low fitness and to a lesser degree low muscle strength were independently associated with an increased future stroke risk.

Cardiovascular and cognitive fitness at age 18 and risk of early-onset dementia.

Patients with early-onset dementia are a significantly under-recognized subgroup of patients with an increasing prevalence. Epidemiological studies are limited and studies of modifiable risk factors, such as physical fitness, are lacking. We aimed to investigate the associations between cardiovascular fitness individually and in combination with cognitive performance at age 18 and risk of early-onset dementia and mild cognitive impairment later in life. We performed a population-based cohort study of over 1.1 million Swedish, 18-year-old, male conscripts, who underwent conscription exams between 1968 and 2005. These males were then followed for up to 42 years. Objective data on cardiovascular fitness and cognitive performance were collected during conscription exams and were subsequently linked with hospital registries to calculate later risk of early-onset dementia and mild cognitive impairment using Cox proportional hazards models controlling for several confounders. The scores from the exams were divided into tertiles (low, medium, high) for the analyses. The mean follow-up time for the analyses was 25.7 years (standard deviation: 9.3) and the median was 27 years. In total, 30 195 315 person-years of follow-up were included in the study. In fully adjusted models, both low cardiovascular fitness and cognitive performance (compared to high) at age 18 were associated with increased risk for future early-onset dementia (cardiovascular fitness, n = 662 events: hazard ratio 2.49, 95%, confidence interval 1.87-3.32; cognitive performance, n = 657 events: hazard ratio 4.11, 95%, confidence interval 3.19-5.29) and mild cognitive impairment (cardiovascular fitness, n = 213 events: hazard ratio 3.57, 95%, confidence interval 2.23-5.74; cognitive performance, n = 212 events: hazard ratio 3.23, 95%, confidence interval 2.12-4.95). Poor performance on both cardiovascular fitness and cognitive tests was associated with a >7-fold (hazard ratio 7.34, 95%, confidence interval 5.08-10.58) and a >8-fold (hazard ratio 8.44, 95%, confidence interval 4.64-15.37) increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively. In conclusion, lower cardiovascular fitness and cognitive performance in early adulthood were associated with an increased risk of early-onset dementia and mild cognitive impairment later in life, and the greatest risks were observed for individuals with a combination of low cardiovascular fitness and low cognitive performance.

Cardiovascular fitness and later risk of epilepsy: a Swedish population-based cohort study.

OBJECTIVE: To analyze the associations between cardiovascular fitness at age 18 years and future risk of epilepsy. METHODS: Population-based cohort study of Swedish male conscripts (n = 1,173,079) born in 1950-1987, who were followed for up to 40 years. Data on cardiovascular fitness were collected during conscription exams and linked with hospital registers to calculate later risk of epilepsy using Cox proportional hazard models controlling for several confounders, including familial factors. RESULTS: Epilepsy was recorded in 6,796 individuals during the follow-up time. In fully adjusted models, low and medium cardiovascular fitness (compared with high) at age 18 years was associated with increased risk of future epilepsy (hazard ratio 1.79, 95% confidence interval 1.57-2.03; and hazard ratio 1.36, 95% confidence interval 1.27-1.45, respectively). The associations changed only marginally after adjustment for familial influences and prior severe traumatic brain injury, cerebrovascular disease, or diabetes. CONCLUSIONS: Low cardiovascular fitness early in life is associated with an increased risk of epilepsy later in adulthood. These results agree with previous results from animal models. We propose that behaviors that increase cardiovascular fitness may act as positive disease-modifiers for the development of epilepsy.