Sex differences in prevalence and characteristics of imaging detected atherosclerosis - a population-based study.

AIMS: Men are more likely to suffer a myocardial infarction than women, but population-based studies on sex differences in imaging detected atherosclerosis are lacking. The aims were to assess sex differences in prevalence of imaging detected coronary and carotid atherosclerosis, as well as multivariable adjusted associations between sex and atherosclerosis. METHODS AND RESULTS: Participants aged 50-65, recruited from the general population to the Swedish Cardiopulmonary bioImage Study (SCAPIS), were included in this population-based cross-sectional study. Comprehensive diagnostics, including coronary computed tomography angiography and carotid ultrasound, were performed. The image findings were any coronary atherosclerosis, coronary stenosis ≥50%, segment involvement score (SIS) ≥4, coronary artery calcium score (CACS) ≥100, and any ultrasound-detected carotid plaque.In 25,580 participants (50% women), men had more hypertension (20.3% vs 17.0%), hyperlipidaemia (9.0% vs 5.5%), and diabetes (8.5% vs 4.7%). The prevalence was 56.2% vs 29.5% for any coronary atherosclerosis (p<0.01), 9.0% vs 2.3% for coronary stenosis ≥50% (p<0.01), 20.2% vs 5.3% for SIS≥4 (p<0.01), 18.2% vs 5.6% for CACS≥100 (p<0.01), and 60.9% vs 48.7% for carotid plaque (p<0.01), in men vs women, respectively. Multivariable adjustment only marginally changed these associations: odds ratios [OR] (95% confidence interval [CI]): 2.75 (2.53-2.99) for coronary atherosclerosis, 2.88 (2.40-3.45) for coronary stenosis ≥50%, 3.99 (3.50-4.55) for SIS≥4, 3.29 (2.88-3.75), for CACS≥100, and 1.57 (1.45-1.70) for carotid plaque. CONCLUSION: Men had higher prevalence of imaging detected carotid and coronary atherosclerosis with prevalence in women aged 65 corresponding to men 10-14 years younger. The associations remained after extensive multivariable adjustment.

Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.

RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure. OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population. METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7. RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCO

Diverticular disease and risk of incident major adverse cardiovascular events: A nationwide matched cohort study.

BACKGROUND: An increased risk of cardiovascular disease (CVD) has been reported in patients with diverticular disease (DD). However, there are knowledge gaps about specific risks of each major adverse cardiovascular event (MACE) component. METHODS: This nationwide cohort study included Swedish adults with DD (1987-2017, N=52,468) without previous CVD. DD was defined through ICD codes in the National Patient Register and colorectal histopathology reports from the ESPRESSO study. DD cases were matched by age, sex, calendar year and county of residence to ≤5 population reference individuals (N=194,525). Multivariable-adjusted hazard ratios (aHRs) for MACE up until December 2021 were calculated using stratified Cox proportional hazard models. RESULTS: Median age at DD diagnosis was 62 years and 61% were females. During a median follow-up of 8.6 years, 16,147 incident MACE occurred in individuals with DD, and 48,134 in reference individuals (incidence rates (IRs)=61.4 vs. 43.8/1,000 person-years) corresponding to an aHR of 1.24 (95%CI=1.22-1.27), equivalent to one extra case of MACE for every 6 DD patients followed for 10 years. The risk was increased for ischemic heart disease (IR=27.9 vs. 18.6; aHR=1.36, 95%CI=1.32-1.40), congestive heart failure (IR=23.2 vs. 15.8; aHR=1.26, 95%CI=1.22-1.31), and stroke (IR=18.0 vs. 13.7; aHR=1.15, 95%CI=1.11-1.19). DD was not associated with cardiovascular mortality (IR=18.9 vs. 15.3; aHR=1.01, 95%CI=0.98-1.05). Results remained robust in sibling-controlled analyses. CONCLUSIONS: Patients with DD had a 24% increased risk of MACE compared with reference individuals, but no increased cardiovascular mortality. Future research should confirm these data and examine underlying mechanisms and shared risk factors between DD and CVD.

Markers of imminent myocardial infarction.

Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case-cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.

Long-Term Incidence of Bradycardia and Pacemaker Implantations Among Cross-Country Skiers: A Cohort Study.

BACKGROUND: Bradycardia is more common among well-trained athletes than in the general population, but the association with pacemaker implantations is less known. We investigated associations of endurance training with incidence of bradycardia and pacemaker implantations, including sex differences and long-term outcome, in a cohort of endurance trained individuals. METHODS: All Swedish skiers who completed >1 race in the cross-country skiing event Vasaloppet between 1989 and 2011 (n=209 108) and a sample of 532 290 nonskiers were followed until first event of bradycardia, pacemaker implantation, or death, depending on end point. The Swedish National Patient Register was used to obtain diagnoses. Cox regression was used to investigate associations of number of completed races and finishing time in Vasaloppet with incidence of bradycardia and pacemaker implantations. In addition, Cox regression was used to investigate associations of pacemaker implantations with death in skiers and nonskiers. RESULTS: Male skiers had a higher incidence of bradycardia (adjusted hazard ratio [aHR], 1.19 [95% CI, 1.05-1.34]) and pacemaker implantations (aHR, 1.17 [95% CI, 1.04-1.31]) compared with male nonskiers. Those who completed the most races and had the best performances exhibited the highest incidence. For female skiers in Vasaloppet, the incidence of bradycardia (aHR, 0.98 [95% CI, 0.75-1.30]) and pacemaker implantations (aHR, 0.98 [95% CI, 0.75-1.29]) was not different from that of female nonskiers. The indication for pacemaker differed between skiers and nonskiers, with sick sinus syndrome more common in the former and third-degree atrioventricular block in the latter. Skiers had lower overall mortality rates than nonskiers (aHR, 0.16 [95% CI, 0.15-0.17]). There were no differences in mortality rates by pacemaker status among skiers. CONCLUSIONS: In this study, male endurance skiers had a higher incidence of bradycardia and pacemaker implantations compared with nonskiers, a pattern not seen in women. Among male skiers, those who completed the most races and had the fastest finishing times had the highest incidence of bradycardia and pacemaker implantations. Within each group, mortality rates did not differ in relation to pacemaker status. These findings suggest that bradycardia associated with training leads to a higher risk for pacemaker implantation without a detrimental effect on mortality risk.

Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis: The Swedish CardioPulmonary BioImage Study.

BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.

Evaluating regression and probabilistic methods for ECG-based electrolyte prediction.

Imbalances in electrolyte concentrations can have severe consequences, but accurate and accessible measurements could improve patient outcomes. The current measurement method based on blood tests is accurate but invasive and time-consuming and is often unavailable for example in remote locations or an ambulance setting. In this paper, we explore the use of deep neural networks (DNNs) for regression tasks to accurately predict continuous electrolyte concentrations from electrocardiograms (ECGs), a quick and widely adopted tool. We analyze our DNN models on a novel dataset of over 290,000 ECGs across four major electrolytes and compare their performance with traditional machine learning models. For improved understanding, we also study the full spectrum from continuous predictions to a binary classification of extreme concentration levels. Finally, we investigate probabilistic regression approaches and explore uncertainty estimates for enhanced clinical usefulness. Our results show that DNNs outperform traditional models but model performance varies significantly across different electrolytes. While discretization leads to good classification performance, it does not address the original problem of continuous concentration level prediction. Probabilistic regression has practical potential, but our uncertainty estimates are not perfectly calibrated. Our study is therefore a first step towards developing an accurate and reliable ECG-based method for electrolyte concentration level prediction-a method with high potential impact within multiple clinical scenarios.

Cardiovascular risk factor assessment in late-onset seizures: A study protocol to assess the value of structured intervention.

OBJECTIVE: A growing body of evidence suggests patients with late-onset seizures are at an increased risk of stroke, but the potential for reducing cardiovascular morbidity through risk factor screening and management is unknown. We aim to determine whether individuals with new-onset unprovoked seizures after middle age should undergo vascular risk assessment. The long follow-up needed to assess stroke risk and the known benefit of vascular risk factor modification make a standard RCT logistically and ethically challenging. Instead, we propose and have developed a protocol for a cluster project assessing the effect of vascular risk factor screening in an intervention trial as well as a cohort study. METHODS: Participating neurology clinics will implement standard cardiovascular risk factor assessment into the routine evaluation for individuals aged ≥50 years attending their first specialized consultation after an unprovoked seizure, excluding those with progressive brain disease. The project has two interlinked components: a prospective single group trial, in which risk factor assessment is performed and subsequent management is followed for one year; and a register-based cohort study examining the long-term effects of the intervention on a system level by comparing patients attending initial consultations in the 2 years after start of the study, with patients seen in the four preceding years at the same clinics. ANALYSIS: The primary outcome of the intervention trial is the proportion of patients receiving subsequent pharmacological treatment. The primary outcome of the cohort study is the incidence of acute stroke in the Swedish Stroke Register. ETHICS AND DISSEMINATION: Swedish Ethical Review Authority approval (which is valid for 2 years only) will be sought when funding is obtained. The results will be disseminated through peer-reviewed scientific publications. REGISTRATION DETAILS: The study will be registered at clinicaltrials.gov. PLAIN LANGUAGE SUMMARY: A first seizure in a middle-aged or older person indicates a higher risk of stroke. It is not known whether investigating and treating blood pressure, blood cholesterol, or similar risk factors after a first seizure is an effective way to prevent stroke. A traditional clinical study would need too many patients and it would be unethical not to treat the control group. We have designed a study in which participating neurology departments change their practice to test and treat vascular risk factors. Patients are then compared to historic controls using registered data.

Efficient proton arc optimization and delivery through energy layer pre-selection and post-filtering.

BACKGROUND: Proton arc therapy (PAT) has emerged as a promising approach for improving dose distribution, but also enabling simpler and faster treatment delivery in comparison to conventional proton treatments. However, the delivery speed achievable in proton arc relies on dedicated algorithms, which currently do not generate plans with a clear speed-up and sometimes even result in increased delivery time. PURPOSE: This study aims to address the challenge of minimizing delivery time through a hybrid method combining a fast geometry-based energy layer (EL) pre-selection with a dose-based EL filtering, and comparing its performance to a baseline approach without filtering. METHODS: Three methods of EL filtering were developed: unrestricted, switch-up (SU), and switch-up gap (SU gap) filtering. The unrestricted method filters the lowest weighted EL while the SU gap filtering removes the EL around a new SU to minimize the gantry rotation braking. The SU filtering removes the lowest weighted group of EL that includes a SU. These filters were combined with the RayStation dynamic proton arc optimization framework energy layer selection and spot assignment (ELSA). Four bilateral oropharyngeal and four lung cancer patients' data were used for evaluation. Objective function values, target coverage robustness, organ-at-risk doses and normal tissue complication probability evaluations, as well as comparisons to intensity-modulated proton therapy (IMPT) plans, were used to assess plan quality. RESULTS: The SU gap filtering algorithm performed best in five out of the eight cases, maintaining plan quality within tolerance while reducing beam delivery time, in particular for the oropharyngeal cohort. It achieved up to approximately 22% and 15% reduction in delivery time for oropharyngeal and lung treatment sites, respectively. The unrestricted filtering algorithm followed closely. In contrast, the SU filtering showed limited improvement, suppressing one or two SU without substantial delivery time shortening. Robust target coverage was kept within 1% of variation compared to the PAT baseline plan while organs-at-risk doses slightly decreased or kept about the same for all patients. CONCLUSIONS: This study provides insights to accelerate PAT delivery without compromising plan quality. These advancements could enhance treatment efficiency and patient throughput.

Risk of heart failure in inflammatory bowel disease: a Swedish population-based study.

BACKGROUND AND AIMS: Dysregulation of inflammatory and immune responses has been implicated in the pathogenesis of heart failure (HF). But even if inflammation is a prerequisite for inflammatory bowel disease (IBD), little is known about HF risk in IBD. METHODS: In this Swedish nationwide cohort, patients with biopsy-confirmed IBD were identified between 1969 and 2017 [n = 81 749, Crohn's disease (CD, n = 24 303), ulcerative colitis (UC, n = 45 709), and IBD-unclassified (IBD-U, n = 11 737)]. Each patient was matched with up to five general population reference individuals (n = 382 190) and IBD-free full siblings (n = 95 239) and followed until 31 December 2019. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) and standardized cumulative incidence for HF, with 95% confidence intervals (CI). RESULTS: There were 5582 incident HF identified in IBD patients (incidence rate [IR]: 50.3/10 000 person-years) and 20 343 in reference individuals (IR: 37.9) during a median follow-up of 12.4 years. IBD patients had a higher risk of HF than reference individuals (aHR 1.19, 95% CI 1.15-1.23). This increased risk remained significant ≥20 years after IBD diagnosis, leading to one extra HF case per 130 IBD patients until then. The increased risk was also observed across IBD subtypes: CD (IR: 46.9 vs. 34.4; aHR 1.28 [1.20-1.36]), UC (IR: 50.1 vs. 39.7; aHR 1.14 [1.09-1.19]), and IBD-U (IR: 60.9 vs. 39.0; aHR 1.28 [1.16-1.42]). Sibling-controlled analyses showed slightly attenuated association (IBD: aHR 1.10 [1.03-1.19]). CONCLUSIONS: Patients with IBD had a moderately higher risk of developing HF for ≥20 years after IBD diagnosis than the general population.

Eosinophilic esophagitis and risk of incident major adverse cardiovascular events: a nationwide matched cohort study.

BACKGROUND: Inflammatory diseases have been associated with an increased cardiovascular risk. However, data on incident major adverse cardiovascular events (MACE) from large population-based cohorts of patients with eosinophilic esophagitis (EoE) is lacking. METHODS: This study included all Swedish adults with EoE without a record of previous cardiovascular disease (CVD) (1990-2017, N = 1546) with follow-up until 2019. Individuals with EoE were identified from prospectively recorded histopathology reports from all Swedish pathology departments (n = 28). EoE patients were matched at index date for age, sex, calendar year and county with up to five general population reference individuals (N = 7281) without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACE (ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. Full sibling comparisons and adjustment for cardiovascular medication were performed. RESULTS: During a median follow-up of 6.0 years, we observed 65 incident MACE in patients with EoE (6.4/1000 person-years (PY)) and 225 in reference individuals (4.7/1000 PY). EoE was not associated with a higher risk of MACE (aHR = 1.14, 95% CI = 0.86-1.51) or any of its components. No differences between age, sex and follow-up time were observed. The results remained stable in sensitivity analyses, including when adjusting for relevant cardiovascular medications and a full sibling comparison. CONCLUSIONS: In this large population-based cohort study, patients with EoE had no increased risk of MACE compared to reference individuals and full siblings. The results are reassuring for patients with EoE.

Toward a Universal Definition of Etiologies in Heart Failure: Categorizing Causes and Advancing Registry Science.

Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.

Are there lost opportunities in chronic kidney disease? A region-wide cohort study.

OBJECTIVES: Identify the windows of opportunity for the diagnosis of chronic kidney disease (CKD) and the prevention of its adverse outcomes and quantify the potential population gains of such prevention. DESIGN AND SETTING: Observational, population-wide study of residents in the Stockholm and Skåne regions of Sweden between 1 January 2015 and 31 December 2020. PARTICIPANTS: All patients who did not yet have a diagnosis of CKD in healthcare but had CKD according to laboratory measurements of CKD biomarkers available in electronic health records. OUTCOME MEASURES: We assessed the proportions of the patient population that received a subsequent diagnosis of CKD in healthcare, that used guideline-directed pharmacological therapy (statins, renin-angiotensin aldosterone system inhibitors (RAASi) and/or sodium-glucose cotransporter-2 inhibitors (SGLT2i)) and that experienced adverse outcomes (all-cause mortality, cardiovascular mortality or major adverse cardiovascular events (MACE)). The potential to prevent adverse outcomes in CKD was assessed using simulations of guideline-directed pharmacological therapy in untreated subsets of the study population. RESULTS: We identified 99 382 patients with undiagnosed CKD during the study period. Only 33% of those received a subsequent diagnosis of CKD in healthcare after 5 years. The proportion that used statins or RAASi was of similar size to the proportion that didn't, regardless of how advanced their CKD was. The use of SGLT2i was negligible. In simulations of optimal treatment, 22% of the 21 870 deaths, 27% of the 14 310 cardiovascular deaths and 39% of the 22 224 MACE could have been avoided if every patient who did not use an indicated medication for their laboratory-confirmed CKD was treated with guideline-directed pharmacological therapy for CKD. CONCLUSIONS: While we noted underdiagnosis and undertreatment of CKD in this large contemporary population, we also identified a substantial realisable potential to improve CKD outcomes and reduce its burden by treating patients early with guideline-directed pharmacological therapy.

Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction.

BACKGROUND: Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists. METHODS: In a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction. RESULTS: From September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no-beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P = 0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no-beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%. CONCLUSIONS: Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.).

Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

Reference ranges for ambulatory heart rate measurements in a middle-aged population.

BACKGROUND: Elevated heart rate (HR) predicts cardiovascular disease and mortality, but there are no established normal limits for ambulatory HR. We used data from the Swedish CArdioPulmonary Imaging Study to determine reference ranges for ambulatory HR in a middle-aged population. We also studied clinical correlates of ambulatory HR. METHODS: A 24-hour ECG was registered in 5809 atrial fibrillation-free individuals, aged 50-65 years. A healthy subset (n=3942) was used to establish reference values (excluding persons with beta-blockers, cardiovascular disease, hypertension, heart failure, anaemia, diabetes, sleep apnoea or chronic obstructive pulmonary disease).Minimum HR was defined as the lowest 1-minute HR. Reference ranges are reported as means±SDs and 2.5th-97.5th percentiles. Clinical correlates of ambulatory HR were analysed with multivariable linear regression. RESULTS: The average mean and minimum HRs were 73±9 and 48±7 beats per minute (bpm) in men and 76±8 and 51±7 bpm in women; the reference range for mean ambulatory HR was 57-90 bpm in men and 61-92 bpm in women. Average daytime and night-time HRs are also reported. Clinical correlates, including age, sex, height, body mass index, physical activity, smoking, alcohol intake, diabetes, hypertension, haemoglobin level, use of beta-blockers, estimated glomerular filtration rate, per cent of predicted forced expiratory volume in 1 s and coronary artery calcium score, explained <15% of the interindividual differences in HR. CONCLUSION: Ambulatory HR varies widely in healthy middle-aged individuals, a finding with relevance for the management of patients with a perception of tachycardia. Differences in ambulatory HR between individuals are largely independent of common clinical correlates.

Usefulness of Heart Failure Categories Based on Left Ventricular Ejection Fraction.

BACKGROUND: Heart failure guidelines have recently introduced a narrow category with mildly reduced left ventricular ejection fraction (LVEF) (heart failure with mildly reduced ejection fraction; LVEF 41%-49%) between the previous categories of reduced (heart failure with reduced ejection fraction; LVEF ≤40%) and preserved (heart failure with preserved ejection fraction; LVEF ≥50%) ejection fraction. Grouping of continuous measurements into narrow categories can be questioned if their variability is high. METHODS AND RESULTS: We constructed a cohort of all 9716 new cases of chronic heart failure with an available LVEF in Stockholm, Sweden, from January 1, 2015, until December 31, 2020. All values of LVEF were collected over time, and patients were followed up until death, moving out of Stockholm, or end of study. Mixed models were used to quantify within-person variance in LVEF, and multistate Markov models, with death as an absorbing state, to quantify the stability of LVEF categories. LVEF values followed a normal distribution. The SD of the within-person variance in LVEF over time was 7.4%. The mean time spent in any LVEF category before transition to another category was on average <1 year for heart failure with mildly reduced ejection fraction. Probabilities of transitioning between categories during the first year were substantial; patients with heart failure with mildly reduced ejection fraction had a probability of <25% of remaining in that category 1 year later. CONCLUSIONS: LVEF follows a normal distribution and has considerable variability over time, which may impose a risk for underuse of efficient treatment. The heart failure with mildly reduced ejection fraction category is especially inconstant. Assumptions of a patient's current LVEF should take this variability and the normal distribution of LVEF into account.

Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.

BACKGROUND: Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population. METHODS: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease. RESULTS: We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers. CONCLUSION: Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

Long-term risk of myocarditis in patients with inflammatory bowel disease: a nationwide cohort study in Sweden.

OBJECTIVES: Despite a suggested link between inflammatory bowel disease (IBD) and myocarditis, the association has not been well-established. This study aimed to investigate the long-term risk of myocarditis in patients with IBD. METHODS: This nationwide cohort involved all patients with biopsy-confirmed IBD in Sweden (1969-2017) (n=83,264, Crohn's disease [CD, n=24,738], ulcerative colitis [UC, n=46,409], and IBD-unclassified [IBD-U, n=12,117]), general population reference individuals (n=391,344), and IBD-free full siblings (n=96,149), and followed until 2019. Primary outcome was incident myocarditis and secondary outcome was severe myocarditis (complicated with heart failure, death, or readmission). Flexible parametric survival models were used to estimate adjusted hazard ratios (aHR) and cumulative incidence of outcomes, along with 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12 years, there were 256 myocarditis cases in IBD patients (incidence rate [IR]=22.6/100,000 person-years) and 710 in reference individuals (IR=12.9), with an aHR of 1.55 (95%CI: 1.33 to 1.81). The increased risk persisted through 20 years after IBD diagnosis, corresponding to one extra myocarditis case in 735 IBD patients until then. This increased risk was observed in CD (aHR=1.48 [1.11 to 1.97]) and UC (aHR=1.58 [1.30 to 1.93]). IBD was also associated with severe myocarditis (IR: 10.1 vs. 3.5; aHR=2.44 [1.89 to 3.15]), irrespective of IBD subtypes (CD: aHR=2.39 [1.43 to 4.01], UC: aHR=2.82 [1.99 to 4.00], and IBD-U: aHR=3.14 [1.55 to 6.33]). Sibling comparison analyses yielded similar results. CONCLUSIONS: Patients with IBD had an increased risk of myocarditis, especially severe myocarditis, for ≥20 years after diagnosis, but absolute risks were low.