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Previous research on cardiometabolic risk has mostly used a variable-centred approach, assessing risk factors separately or in predefined combinations. This study used a probabilistic modelling approach to identify distinct cardiometabolic risk classes and estimate the predicted prevalence of subclinical atherosclerosis. The analysis included 28,307 middle-aged adults from the Swedish CArdioPulmonary bioImage Study (2013-2018), linked to national registers. Eleven risk factors were assessed: smoking, alcohol consumption, sodium and fibre intake, physical activity, stress, waist circumference, triglycerides, HDL-cholesterol, blood pressure, and fasting glucose. Subclinical atherosclerosis was defined using coronary artery calcium (CAC) scores and the presence of carotid plaque. A three-step latent class analysis identified four cardiometabolic risk classes: "low fibre intake and normolipidemia" (55.2%, Class 1), "high sodium intake and normolipidemia" (12.8%, Class 2), "unhealthy lifestyle and heightened metabolic risk" (10.1%, Class 3), and "unhealthy lifestyle and high metabolic risk" (21.9%, Class 4). Predicted mean CAC scores ranged from 42.6 (Class 2, 95% CI 39.0-46.3) to 92.1 (Class 4, 95% CI 86.2-98.0). Predicted carotid plaque prevalence ranged from 51.6% (Class 2, 95% CI 50.6-52.6) to 60.8% (Class 4, 95% CI 59.8-61.9). Latent classes offered a complementary descriptive framework beyond single risk factors, supporting more tailored prevention according to risk profiles.

Clonal hematopoiesis of indeterminate potential (CHIP), defined by somatic mutations in hematopoietic cells without overt malignancy, is linked to increased risks of hematologic malignancies, cardiovascular disease, and mortality. However, the contribution of environmental exposures and lifestyle factors remains poorly understood.

Our exploratory study characterized early-stage CHIP using a variant allele frequency cut-off > 0.1% in 888 well-phenotyped 70-year-olds leveraging ultra-deep targeted sequencing (mean coverage 8331X). Associations with dietary patterns, specific nutrient intakes, persistent organic pollutants (POPs), per- and polyfluoroalkyl substances (PFAS), heavy metals, and germline variants were evaluated.

The prevalence of early-stage CHIP was 41.0%. Elevated blood cadmium levels were associated with an increased prevalence of non-DTA-CHIP (mutations occurring outside of DNMT3A, TET2, and ASXL1, odds ratio (OR) 2.13, 95% confidence interval (CI) 1.32–3.45), especially TP53-CHIP (OR 3.34, 95% CI 1.65–6.72). PCB-189 levels were positively linked to DNMT3A-CHIP (OR 1.42, 95% CI 1.13–1.79). Healthy dietary patterns were associated with decreased odds of TET2-CHIP (OR 0.88, 95% CI 0.78–0.98) whereas increased odds for TET2-CHIP were observed for higher intakes of vitamin B2 (OR 2.07, 95% CI 1.17–3.69). Higher intakes of vitamins B2 and B6 as well as smoking were associated with an increased prevalence of non-DTA CHIP (OR 2.35, 95% CI 1.03–5.33, OR 2.05, 95% CI 1.03–4.05, and OR 3.17, 95% CI 1.43–6.64, respectively).

Our exploratory study suggests that the exposome may influence clonal selection in the bone marrow, but future studies are required to validate these factors and determine their clinical significance.

Disruptions in gut microbiome are implicated in cardiometabolic disorders and other health outcomes. Antibiotics are known gut microbiome disruptors, but their long-term consequences remain underexplored. Here we combined individual-level data from the Swedish Prescribed Drug Register with fecal metagenomes of 14,979 adults to examine the association between oral antibiotic use over 8 years and gut microbiome. In multivariable confounder-adjusted regression models, antibiotic use <1 year before fecal sampling was associated with the greatest reduction in species diversity, but significant associations were also observed for use 1-4 and 4-8 years earlier. Clindamycin, fluoroquinolones and flucloxacillin accounted for most of the associations with the abundance of individual species. Use of these antibiotics 4-8 years earlier was associated with altered abundance of 10-15% of the species studied; penicillin V, extended-spectrum penicillins and nitrofurantoin were associated with only a few species. Similar results were found comparing one antibiotic course 4-8 years before sampling versus none in the past 8 years. These findings indicate that antibiotics may have long-lasting consequences for the gut microbiome.

Background and importance

Crowded emergency departments (EDs) and long waiting times may lead to delayed care for acute conditions and increased mortality in patients leaving without being seen by a physician (LWBS).

Objectives

The aim of this study was to characterize patients LWBS from the ED at a Swedish university hospital and report their mortality.Design, setting, and participantsA cohort study was conducted. Data from electronic medical records of patients LWBS (exposure) were compared with those who stayed through completion of treatment. Data were gathered from 151 228 patients making 363 308 visits to the Uppsala University Hospital ED from 1 January 2010 to 30 June 2017.

Outcome measures and analysis

Short- and long-term mortality of patients LWBS were studied using Cox regression analysis. Sex, age, triage level, arrival mode, length of stay, presenting complaint, crowding, and time of day were assessed as regards effect on the probability of LWBS and as covariates in the mortality analysis.

Results

In our dataset, 9058 patient visits to the ED (2.5% of all ED visits) ended in LWBS. These patients were younger than average and had lower triage levels. No significant difference was found between males and females. The highest rates were seen in patients presenting with a psychiatric disorder (12.8%), victims of physical assault (11.7%), or alcohol/drug withdrawal (9.9%). The likelihood of LWBS was highest in the evening and lowest in the early morning. Short-term mortality at 28 days was not significantly affected by LWBS, but a 34% lower long-term mortality risk was seen for patients LWBS (hazard ratio 0.66, 95% confidence interval 0.45-0.95, P = 0.028) in median follow-up of 3.5 years.

Conclusion

Patients LWBS were younger, had lower triage levels, and more frequently presented with psychiatric or substance use-related complaints. They had lower short- and long-term mortality compared with those who completed treatment. This observation does not imply a causal relationship but highlights differences in patient characteristics.

IMPORTANCE: Risk stratification strategies in primary prevention of coronary events lack precision.

OBJECTIVE: To determine whether prediction of first coronary events is improved by adding information on coronary atherosclerosis from coronary computed tomography angiography (CCTA) to a model using the pooled cohort equation (PCE) risk score tool and the coronary artery calcification score (CACS).

DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study including individuals aged 50 to 64 years randomly recruited from the general population and examined at 6 university hospitals in Sweden from 2013 to 2018, with a median follow-up of 7.8 years. A sample of 30 154 individuals underwent cardiopulmonary imaging, physical examinations, routine laboratory tests, questionnaires, and/or functional tests. This study included 24 791 individuals without previous cardiovascular disease for whom high-quality CCTA images were available. Events were followed up via registers until September 2024.

EXPOSURES: The information used from the CCTA images was the extent of coronary atherosclerosis (segment involvement score), presence of noncalcified atherosclerosis, and presence of coronary obstructive disease (stenosis ≥50%).

MAIN OUTCOMES AND MEASURES: The outcome was a composite of first occurrence of nonfatal myocardial infarction or death from coronary heart disease.

RESULTS: During follow-up, 304 coronary events occurred. Segment involvement scores of 3 to 4 and greater than 4 and presence of noncalcified atherosclerosis were associated with hazard ratios of 2.71 (95% CI, 1.34-5.44), 5.27 (95% CI, 2.50-11.07), and 1.66 (95% CI, 1.23-2.22), respectively. In a model based on the PCE and CACS, CCTA-derived data improved risk discrimination (C statistic improved from 0.764 to 0.779; P = .004) and risk reclassification (net reclassification improvement of 0.133 [95% CI, 0.031-0.165]), conferred a net correct upward reclassification of 14.2% in those with events and incorrectly classified 1.6% of participants not experiencing an event into a higher-risk category. Because of the low event rate in the cohort, reclassification mainly occurred in the group classified as at low risk (<5%) according to the PCE.

CONCLUSIONS AND RELEVANCE: Information on coronary atherosclerosis from CCTA modestly improved risk prediction beyond traditional risk factors and CACS in identifying individuals at risk of coronary events and in need of primary prevention.

Aims: Congestive heart failure (CHF) is associated with increased mortality. Early identification of individuals at risk for CHF may improve the poor prognosis. Decreased baroreceptor sensitivity (BRS) has been related to higher mortality in CHF. The aim was therefore to explore whether decreased BRS could identify patients at risk for the development of CHF.

Methods and Results: The PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study (1016 individuals, all aged 70 years) was used for analysis of baroreceptor sensitivity, measured by sequence analysis (BRS_seq) and spectral analysis (BRSαHF and BRSαLF). During 15 years of follow-up, 98/844 individuals developed CHF. Both decreased and increased BRS_seq were associated with incident CHF (p = 0.027) after multiple adjustments. A similar pattern was seen for BRSαHF (p = 0.017) in a sex-adjusted model, but not after multiple adjustment, while BRSαLF was unrelated to incident CHF.

Conclusion: A decreased BRS was associated with incident CHF in an elderly population. An increased BRS was also found, although to a lesser degree, to be linked to CHF, which was a novel finding. If reproduced in further studies, BRS might prove to be useful for an early identification of CHF in clinical practice.

BACKGROUND: The ambulatory arterial stiffness index (AASI) is increasingly used in clinical research and practice. This individual-participant meta-analysis aims to consolidate the prognostic accuracy of AASI in the general population and to derive an end point-based AASI risk threshold. METHODS: In 12 558 individuals enrolled in 14 population studies (48.8% women; mean age, 59.3 years), AASI was derived by regressing 24-hour diastolic on systolic blood pressure (mm Hg/mm Hg). Using Cox regression, the risk-carrying AASI threshold was established by examining stepwise increasing AASI levels and by determining the AASI level, yielding a 10-year risk similar to an office systolic pressure of 140 mm Hg. RESULTS: Over 10.7 years (median), 3027 all-cause deaths and 2183 cardiovascular end points occurred. In all participants, multivariable-adjusted hazard ratios expressing the all-cause deaths and cardiovascular end point risk per 1-SD AASI increment were 1.08 (95% CI, 1.04-1.13) and 1.13 (95% CI, 1.07-1.18). In a randomly defined subset of 8189 individuals, the risk-carrying AASI thresholds converged to 0.50 with hazard ratios (>= 0.50 versus <0.50) of 1.14 (95% CI, 1.04-1.26) for all-cause deaths and 1.13 (95% CI, 1.01-1.26) for cardiovascular end point. In the replication sample (n=4369), these hazard ratios were 1.13 (95% CI, 1.01-1.26) and 1.19 (95% CI, 1.04-1.35). AASI continuous or per threshold significantly improved model performance. Analyses of secondary end points and subgroups stratified by sex, age, hypertension status and treatment, history of cardiovascular disease, and nocturnal dipping were confirmatory. CONCLUSIONS: Over and beyond traditional risk factors, AASI improves risk stratification. Exceeding the risk-carrying 0.50 AASI threshold necessitates increased vigilance in managing risk factors before irreversible cardiovascular complications occur.

Background: A reduction in kidney function cause metabolites that normally are cleared by the kidney to accumulate. These accumulated metabolites could potentially link kidney function to an increased risk of cardiovascular disease.

Aim: To assess the relationships between creatinine-based estimated glomerular filtration rate (eGFR) and the metabolome (791 endogenous metabolites) in the general population, as well as the cortisol to cortisone ratio.

Patients and methods: Three population-based cohorts, Epihealth, PIVUS and POEM (total n = 3,444), were used with a discovery/validation approach. Metabolomics was measured by mass spectroscopy. eGFR was calculated using the 2021 CKD-EPI creatinine-based equation. Multivariable linear regression was used to assess the correlations between each metabolite concentration and eGFR, adjusting for sex, % fat mass, cardiovascular risk factors and medications. The metabolites significant in the linear regression were analyzed using MultiVariable Mendelian Randomization (MVMR), adjusting for diabetes and BMI.

Results: Nighty-six metabolites were significantly associated to eGFR and had the same direction of association in both linear regression and MVMR. The vast majority of these associations were negative. Apart from creatinine, N-acetylalanine, N,N-dimethyl-pro-pro, N,N,N-trimethyl-alanylproline betaine (TMAP) were the top findings. Pathway enrichment analysis (Metaboloanalyst 6.0) found five significantly enriched pathways, two of which involved amino acid metabolism.

Conclusions: In a general population with only mild to moderately reduced kidney function, several metabolites were associated with kidney function, including the cortisol to cortisone ratio. This finding is of interest since several of these metabolites might link reduced kidney function to an increased risk of cardiovascular disease.

Cardiometabolic diseases often cluster as multimorbidity, yet current risk prediction models typically focus on a single disease and rarely incorporate social determinants. This study aims to develop a Bayesian risk prediction model for cardiometabolic multimorbidity in middle-aged Swedish adults. This prospective cohort included 11,964 adults without prior cardiometabolic disease from the Swedish CArdioPulmonary bioImage Study (SCAPIS; enrolment 2013-2016). Cardiometabolic disease was defined as incident type 2 diabetes (T2D), ischaemic heart disease/heart failure, or stroke. Regularised Bayesian logistic regression models were developed to predict any cardiometabolic disease (>= 1 condition) and cardiometabolic multimorbidity (>= 2 conditions) within 2-5 years. Twenty-two social and cardiometabolic risk predictors were considered. During follow-up, 6.0% of participants developed cardiometabolic disease(s) (5.7% with a single cardiometabolic disease and 0.3% with multimorbidity). The prediction model showed fair discrimination for any cardiometabolic disease (AUC 0.76, 95% CI 0.74-0.78) and good discrimination for multimorbidity (AUC 0.89, 95% CI 0.86-0.93). The highest predicted risks were observed among older foreign-born males with hypertension, low HDL-C, high waist circumference, and current/ex-smoker, with predicted risks of 34.7% (95% CrI 30.3%-39.5%) for any cardiometabolic disease and 4.4% (95% CrI 2.0%-7.9%) for multimorbidity. These findings suggest that social determinants and uncertainty estimates may provide useful information for cardiometabolic disease prediction, though further validation is needed before use in clinical practice.

Global reporting of obesity is commonly based on comparisons over multiple decades1 and lacks a granular and systematic analysis of its dynamics. We used 4,050 population-based studies with measured height and weight data on 232 million participants to assess the worldwide dynamics of obesity from 1980 to 2024. The rise in obesity decelerated in school-aged children and adolescents throughout the 1990s in many high-income countries, and subsequently plateaued in most at age-standardized prevalences spanning 20 percentage points, from 3-4% for girls in Japan, Denmark and France to 23% for boys in the USA. There were indications of a small decline in obesity in children and adolescents in some high-income western countries (for example, Italy, Portugal and France) since the 2000s. Similar trends were seen in some countries in Central and Eastern Europe. In adults, the rise in obesity slowed down in high-income western countries about a decade after children, followed by a plateau or possibly a small reversal of the rise in some countries (for example, Spain). In most low-income and middle-income countries, the annual absolute change in prevalence has remained stable or increased over time, even though prevalence has surpassed that of high-income countries. These highly varied dynamics suggest that the social, economic and technological trends that influence the availability, affordability and use of different foods may have helped control the rise in obesity in high-income countries, but require policy interventions in low-income and middle-income countries.