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Objective: To investigate the relationship between active commuting and atherosclerosis in middle age using state-of-the-art coronary CT angiography (CCTA).

Methods: This cross-sectional study used data from the Swedish CArdioPulmonary bioImage Study (SCAPIS) and included 23 722 randomly recruited individuals aged 50-64 years from six different regions in Sweden. The exposure was commuting mode, assessed using self-reported questionnaires and categorised as year-round walking and/or cycling (active commuting), commuting by bus/train, commuting by car or mixed commuting patterns. The outcome was atherosclerosis, evaluated using CCTA for coronary stenosis and coronary artery calcium (CAC) score and ultrasound for carotid plaques. Associations were analysed using multivariate binomial logistic regression models.

Results: After adjusting for confounders (age, sex, SCAPIS site, education, occupational physical activity and leisure time exercise habits, sleep, diet and smoking habits), active commuting was associated with lower odds of coronary stenosis (OR 0.87; 95% CI 0.80 to 0.94) and a CAC score >= 1 Agatston units (OR 0.93; 95% CI 0.86 to 1.00), as compared with car commuting. No associations were observed between active commuting and the presence of carotid plaques (OR 0.97; 95% CI 0.90 to 1.03). When stratified, the inverse association with coronary stenosis appeared to be somewhat stronger for cycling (OR 0.86; 95% CI 0.78 to 0.95) than for walking (OR 0.89; 95% CI 0.79 to 1.01).

Conclusion: Using advanced CCTA imaging in a large, randomly selected sample of middle-aged adults, we show for the first time that coronary atherosclerosis is less common in active commuters, particularly those cycling, compared with car commuters. While this indicates that active commuting might be a potential preventive measure to reduce atherosclerosis and subsequent cardiovascular disease, further causal analyses are needed to confirm our findings.

Background

Young athletes and adolescents with high cardiorespiratory fitness appear to have a higher risk of atrial fibrillation (AF), but the extent to which this reflects causal effects or shared genetic, behavioral, and environmental factors remains uncertain.

Methods

This cohort study with sibling control analysis comprised Swedish men who participated in mandatory military conscription examinations from 1972 to 1995 and completed cardiorespiratory fitness testing. The outcomes were AF and non-AF cardiovascular disease (CVD; eg, stroke and ischemic heart disease), defined as a composite end point of diagnosis or death in the National Patient Register and the Cause of Death Register, until December 31, 2023. Flexible parametric survival models estimated standardized cumulative risk differences (RDs) by deciles of fitness.

Results

Among 1 124 049 men (mean age, 18.3 years), 45 179 (4.0%) had a first AF event and 96 404 (8.6%) had a first non-AF CVD event at a median age of 54.8 and 54.4 years. In population-wide analysis controlling for measured confounders, compared with the lowest decile of fitness, the highest decile had a small excess in AF that exceeded the reduction in non-AF CVD during early adulthood, whereas the reduction in non-AF CVD became larger from 45 years of age onwards. In full-sibling comparisons controlling for shared familial factors, the age-dependent trade-off disappeared entirely, leaving no age window with a net cardiovascular disadvantage. Already from 35 years of age, the reduction in non-AF CVD was larger (RD, -0.11% [95% CI, -0.21% to -0.01%]) than the excess in AF (RD, 0.06% [95% CI, -0.01% to 0.12%]). By 65 years of age, the gap further widened, with an even larger reduction in non-AF CVD (RD, -3.91% [95% CI, -5.40% to -2.42%]) compared with the excess in AF (RD, 2.30% [95% CI, 1.15% to 3.45%]).

Conclusions

High adolescent cardiorespiratory fitness is associated with a small excess in AF risk during early adulthood that is outweighed by larger reductions in non-AF CVD after controlling for familial confounders. These findings support population-level efforts to improve youth cardiorespiratory fitness and provide reassurance about the safety and benefits of high fitness levels.

Background

Neurodevelopmental conditions (NDC), including attention deficit/hyperactivity disorder (ADHD) and autism, are associated with increased rates of neurodegenerative diseases, including Alzheimer’s disease and related dementias (ADRD) and Parkinson’s disease. Such associations are unstudied in diverse populations and while controlling for a range of important covariates. The purpose of this study was to examine the association of ADRD and Parkinson’s disease with NDCs in a diverse sample of adults.

Methods

This case-control study used data from the United States All of Us Research Program 2018-2023 from approximately 600 000 adults in the United States. We matched on ADRD and Parkinson’s disease status to examine the association of these conditions with NDCs.

Results

NDC was more prevalent in ADRD cases than in non-ADRD controls (7.8% vs 2.4%) and among Parkinson’s disease cases than non-Parkinson’s disease controls (4.5% vs 1.8%). After adjustment for sex, age, education level, body mass index, cardiometabolic conditions, and psychiatric conditions, individuals with ADRD had significantly higher odds of having an NDC compared with controls (adjusted odds ratio, 2.68; 95% CI, 2.40-2.99). Similarly, Parkinson’s disease cases had 2.09 times the odds of having an NDC as non-Parkinson’s disease controls (95% CI 1.66, 2.59) in adjusted models.

Conclusions

As the population of individuals with NDCs ages, and more older adults find themselves in the care of clinicians with expertise in ADRD and Parkinson’s disease, it is imperative to understand the support needs of this population, and to provide targets for reducing ADRD prevalence in younger or middle adulthood.

Importance  Elevated blood pressure (BP) in adolescence has been linked to higher risk of cardiovascular disease mortality, as well as surrogate markers of atherosclerosis, such as carotid intima-media thickness and coronary artery calcification. However, these markers do not fully capture the complex spectrum of subclinical atherosclerotic cardiovascular disease.

Objective  To examine the association between systolic and diastolic BP in adolescence and atherosclerosis in middle age, measured by coronary computed tomography angiography (CCTA).

Design, Setting, and Participants  This population-based cohort study conducted in Sweden linked BP data from the Swedish Military Conscription Register (1972-1987) during adolescence to atherosclerosis data from the Swedish Cardiopulmonary Bioimage Study (2013-2018) during middle age. Data analyses were performed in May 2025.

Exposure  Adolescent BP was categorized according to the 2025 American College of Cardiology/American Heart Association (ACC/AHA) and the 2024 European Society of Cardiology (ESC) guidelines.

Main Outcomes and Measures  The primary outcome was coronary atherosclerosis, evaluated via CCTA stenosis. The associations were analyzed using multinomial logistic regression, adjusted (marginal) prevalences, and restricted cubic splines.

Results  A total of 10 222 men with mean (SD) age of 18.3 (0.5) years at baseline and median (IQR) age of 57.8 (53.4-61.2) years at follow-up were included. At baseline, mean (SD) systolic BP (SBP) and diastolic BP (DBP) were 127.6 (10.7) mm Hg and 68.3 (9.5) mm Hg, respectively. After a median (IQR) follow-up of 39.5 (35.2-42.8) years, 4159 participants (45.7%) had 1% to 49% coronary stenosis and 784 (8.6%) had 50% or greater coronary stenosis. Elevated BP in adolescence was associated with coronary stenosis in a dose-response fashion. Adolescents with stage 2 hypertension had a higher risk of severe coronary stenosis (≥50%), with an odds ratio of 1.84 (95% CI, 1.40-2.42) and an adjusted prevalence of 10.1% (95% CI, 8.6%-11.5%) compared to those with normal BP (adjusted prevalence, 6.9%; 95% CI, 5.7%-8.1%). Elevated BP categories according to the 2025 ACC/AHA (120-129/<80 mm Hg) and the 2024 ESC (120-139/70-89 mm Hg) were associated with severe coronary atherosclerosis in middle age. The association was stronger for SBP than for DBP.

Conclusions and Relevance  In this population-based cohort study, higher BP levels in adolescence were associated with a dose-dependent higher risk for atherosclerosis in middle age, particularly for severe coronary atherosclerosis. Excess risks of atherosclerosis were even evident in the elevated BP range in adolescence as defined by the 2025 ACC/AHA and 2024 ESC BP guidelines.

Introduction: Accurate prediction of fracture risk is important for treatment decisions, yet evaluations of commonly used thresholds are limited, and the added value of volumetric bone mineral density (vBMD) remains uncertain. We conducted the first head-to-head comparison of the SHAFRE and FRAX algorithms using identical predictor information.

Materials and methods: We included 3525 community-dwelling Swedish men and women (mean age 71.4 years) who underwent a health examination with femoral neck areal BMD (aBMD) and radial vBMD. Incident fractures were retrieved from the National Patient Register. Model performance was evaluated using threshold-specific sensitivity and specificity.

Results: Over a mean follow-up of 8.7 years, 559 participants sustained a fracture. SHAFRE predicted a mean 10-year fracture risk of 21.9% in those who fractured versus 15.6% in the remaining cohort (ROC-area: 68%, 95% CI: 66-71%). Corresponding FRAX values were 16.7% and 12.6% (ROC-area: 66%, 95% CI: 63-68%), and FRAX slightly underestimated fracture risk in this cohort. Adding radial vBMD on top of aBMD did not materially improve discrimination for SHAFRE (70%, 95% CI: 67-72%) or FRAX (68%, 95% CI: 65-70%). Threshold-specific analysis identified an optimal predicted risk threshold of 13-17%, consistently below the commonly recommended 20%.

Conclusions: Predictive ability for major fractures remained modest for both algorithms and was not improved by adding vBMD. The estimated optimal threshold for treatment initiation was lower than the commonly recommended 20%. These findings reinforce that discrimination is substantially stronger for hip fracture than for major osteoporotic fractures.

Differences in antidepressant dispensation across the Nordic countries have been reported, but existing reviews are based on older data. We conducted a systematic review of population-based studies reporting prevalence and/or incidence of antidepressant dispensation in the Nordic countries. Embase, PubMed and Web of Science were searched for studies published between 1 January 2000 and 1 October 2025. Of 2728 screened records, 30 studies with data from 1994 to 2021 were included. Comparisons with Finland and Iceland were not possible due to outdated data. Antidepressant dispensation rates were higher in Sweden than in Denmark and Norway, with differences increasing over time, largely driven by rising rates in Sweden. This pattern was observed across age groups and sexes but was most pronounced among children and adolescents, particularly girls. The most recent data showed approximately 2.0-5.6 times higher prevalence and incidence of antidepressant dispensation in Sweden compared with Denmark and Norway. In 2021, the prevalence per 1000 population among 15- to 19-year-olds was 87.9 for girls and 34.7 for boys in Sweden, compared with 35.8 for girls and 14.5 for boys in Denmark and 31.6 for girls and 12.5 for boys in Norway, with a similar pattern for incidence. For adults, the prevalence pattern was similar, although incidence data were lacking. These findings underscore the need for analytical studies examining factors underlying temporal trends and cross-national differences in antidepressant dispensation, including incidence trends among adults, as well as updated population-based studies from Finland and Iceland to enable comprehensive Nordic comparisons.

Background: Cardiorespiratory fitness has been linked to both lower and higher risks of cancer, but the evidence comes from observational analysis which may be influenced by unobserved confounders and bias processes. We aimed to examine the associations between adolescent cardiorespiratory fitness and risk of cancer in late adulthood while addressing the unknown influence of unobserved familial confounders and diagnostic bias processes.

Methods and findings: We conducted a sibling-controlled cohort study with registry linkage based on all Swedish men who participated in mandatory military conscription examinations from 1972 to 1995 and who completed standardized cardiorespiratory fitness testing. The outcomes were overall cancer diagnosis and cancer mortality, and 14 site-specific cancers (diagnosis or death), ascertained using the National Patient Register and Cause of Death Register until 31 December 2023. A total of 1,124,049 men, including 477,453 full siblings, with a mean age of 18.3 years at baseline, were followed until a median (maximum) age of 55.9 (73.5) years, during which 98,410 were diagnosed with cancer and 16,789 died from cancer (41,293 and 6,908 among full siblings respectively). In cohort analysis, individuals in the highest quartile of fitness had a lower risk of overall cancer mortality (adjusted hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.67, 0.76; P < 0.001) compared to the lowest quartile, corresponding to a standardized cumulative incidence (1-Survival) difference of -0.85 (95% CI [-1.00, -0.71]) percentage points at 65 years of age. Individuals in the highest quartile of fitness also had lower risks (HRs ranging from 0.81 to 0.49, incidence differences ranging from -0.13 to -0.32 percentage points; P < 0.001 for all) of rectum, head and neck, bladder, stomach, pancreas, colon, kidney, liver, bile ducts, and gallbladder, esophagus, and lung cancer. Yet, individuals in the highest quartile of fitness had higher risks of prostate (HR: 1.10, 95% CI [1.05, 1.16]; P < 0.001, incidence difference: 0.48 percentage points, 95% CI [0.23, 0.73]) and skin cancer (e.g., non-melanoma HR: 1.44, 95% CI [1.38, 1.50]; P < 0.001, incidence difference: 1.84 percentage points, 95% CI [1.62, 2.05]). Individuals in the highest quartile of fitness had a higher risk of overall cancer diagnosis (HR: 1.08, 95% CI [1.06, 1.11]; P < 0.001, incidence difference: 1.32 percentage points, 95% CI [0.94, 1.70]), results driven by prostate and skin cancer being the most common types of cancer. When comparing full siblings, and thereby controlling for unobserved shared confounders, the lower risk of overall cancer mortality remained (HR: 0.78, 95% CI [0.68, 0.89]; P < 0.001, incidence difference: -0.61 percentage points, 95% CI [-0.93, -0.28]), while the excess risk of prostate (HR: 1.01, 95% CI [0.90, 1.13]; P = 0867, incidence difference: 0.05 percentage points, 95% CI [-0.50, 0.60]), skin (e.g., non-melanoma HR: 1.09, 95% CI [0.99, 1.20]; P = 0.097, incidence difference: 0.40 percentage points, 95% CI [-0.07, 0.87]), and overall cancer diagnosis (HR: 1.00, 95% CI [0.95, 1.06]; P = 0.921, incidence difference: 0.04 percentage points, 95% CI [-0.80, 0.88]) attenuated to the null. For other site-specific cancers, sibling comparisons results varied, with more attenuation for melanoma, kidney, stomach, bladder, pancreas, and liver, bile ducts, and gallbladder cancer, while associations with lung, colon, head and neck, and esophagus cancer seemed to attenuate less. The findings were confirmed through an extensive set of sensitivity analyses. The main limitations of this study include the lack of inclusion of female participants, lack of data on other risk factors such as smoking, alcohol consumption, and physical activity, and only adjustment for the unobserved confounders which are shared between full siblings.

Conclusions: Higher levels of adolescent cardiorespiratory fitness were associated with lower overall cancer mortality in late adulthood, a finding that persisted in sibling comparisons. However, the influence of unobserved familial confounding appeared to vary by cancer type and be more pronounced for cancer diagnoses than for mortality. This may suggest a need for robust causal methods to triangulate results, rather than relying on correlations alone, to better inform public health efforts.

Objective: To examine the association between adolescent cardiorespiratory fitness and risk of type 2 diabetes in late adulthood, including the potential influence of unobserved familial confounding on the association.

Design: Nationwide sibling controlled cohort study.

Setting: Swedish Military Service Conscription Register, Sweden, 1972-95, with Multi-Generation Register for identifying full siblings. National Patient Register and Prescribed Drug Register for data on diagnoses of type 2 diabetes, deaths from National Cause of Death Register, and Statistics Sweden for emigration and socioeconomic data.

Participants: 1 124 049 Swedish men who participated in mandatory military conscription examinations with completed standardised cardiorespiratory fitness testing. Participants were followed up until 31 December 2023.

Main outcome measures: Type 2 diabetes, defined as a composite endpoint of diagnosis in inpatient or specialist outpatient care and dispensation of antidiabetic drug treatment, until 31 December 2023.

Results: 1 124 049 men, including 477 453 full siblings, with a mean age of 18.3 (standard deviation 0.7) years at baseline were included. During follow-up, 115 958 men (10.3%) and 48 089 full siblings (10.1%) had a first type 2 diabetes event at a median age of 53.4 (interquartile range 47.6-59.3) years. Cardiorespiratory fitness was categorised into deciles (referred to as groups, with group 1 being the lowest fitness level and group 10 the highest). In a cohort analysis, the adjusted hazard ratio in fitness group 2 versus fitness group 1 was 0.83 (95% confidence interval (CI) 0.81 to 0.85), with a difference in the standardised cumulative incidence at age 65 years of 4.3 (95% CI 3.8 to 4.8) percentage points, decreasing to a hazard ratio of 0.38 (0.36 to 0.39; incidence difference 17.8 (17.3 to 18.3) percentage points) in fitness group 10. When comparing full siblings, and thus controlling for all unobserved shared behavioural, environmental, and genetic confounders, the association was replicated, but with a reduction in magnitude. The hazard ratio in fitness group 2 was 0.89 (95% CI 0.85 to 0.94; incidence difference 2.3 (1.3 to 3.3) percentage points) and 0.53 (0.50 to 0.57; incidence difference 10.9 (9.7 to 12.1) percentage points) in fitness group 10. Hypothetically moving all participants in fitness group 1 to fitness group 2 was estimated to prevent 7.2% (95% CI 6.4% to 8.0%) of events at age 65 years in the cohort analysis versus 4.6% (2.6% to 6.5%) in the full sibling analysis, whereas hypothetically moving all participants to fitness group 10 was estimated to prevent 35.6% (34.1% to 37.0%) versus 24.3% (20.5 to 28.0) of events. Indications of effect modification by overweight status were found, where the association was smaller in those with overweight than in those without overweight, particularly in the full sibling analysis.

Conclusions: The findings indicate that adolescent cardiorespiratory fitness could be important in the development of type 2 diabetes in late adulthood, but conventional observational analysis might give biased estimates of the magnitude of the effect.