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Previous research suggests that the use of snus, a smokeless tobacco product, is associated with increased all-cause and cardiovascular mortality, but the underlying mechanisms are unknown. We aimed to evaluate the associations of snus use with biomarkers of cardiometabolic importance: high-sensitivity C-reactive protein (hs-CRP), 25-hydroxyvitamin D (25(OH)D) and calculated free testosterone (cfT). We performed cross-sectional analyses within the population-based Northern Sweden MONICA-study. The study sample consisted of 6 158 never-smoking men and women (of whom 21 and 3.3% were current snus users, respectively), examined between 1990 and 2014. Harmonized analyses on biomarkers were conducted 2016 to 2018. We evaluated the relationships between snus use and biomarker concentrations using linear and logistic regression. Snus use, compared to never-use, was associated with lower hs-CRP (exp(β_ln) 0.88, 95% CI 0.81; 0.96) and 25(OH)D-concentrations (β − 1.01, 95% CI −1.70; −0.33) in mixed-sex analyses. Among men, snus use was also associated with higher cfT-concentrations (exp(β_ln) 1.04, 95% CI 1.01; 1.07). Former snus users had no significant differences in biomarker concentrations. Snus users have lower concentrations of 25(OH)D and hs-CRP, irrespective of sex, while male users have higher cfT-concentrations. These findings may in part contribute to the previously observed increased mortality among snus users.

BACKGROUND: Frailty is common after stroke and linked to poor outcomes, but many measures are clinician-rated, time-consuming, and not suited to patient-reported data. To address these issues, we developed and validated a frailty score from the Swedish Stroke Register (Riksstroke) three-month follow-up questionnaire.

METHODS: We analyzed responses from 19,470 stroke survivors to nine patient-reported items covering function, mood, fatigue, pain and general health, in the 2021-2022 Riksstroke questionnaire. Dimensionality was assessed with Mokken Scale Analysis and exploratory factor analysis. Item response theory (IRT) was used for score computation. Competing graded response IRT models (unidimensional, correlated-factor, bifactor) were compared, and measurement fairness was examined using differential item functioning (DIF) across age, sex, and education. Prognostic validity was tested with Kaplan-Meier curves and Cox regression for all-cause mortality.

RESULTS: From the Mokken Scale Analysis, all items met scalability criteria. Factor analysis suggested two correlated interpretable facets (Physical Functioning; Well-being/Mental Health). A bifactor IRT model provided the best fit to the data, comprising a general frailty dimension while addressing the strong correlation between the facets. DIF was minimal for sex and education, with modest age-related effects. Higher frailty scores were associated with increased mortality in adjusted Cox models and Kaplan-Meier curves. Tools for computing frailty scores are available at https://github.com/joakimwallmark/frailty-irt-scores.

CONCLUSIONS: A robust, fair, and prognostically meaningful frailty score can be derived from patient-reported items in Riksstroke. More broadly, the study demonstrates how routinely collected patient-reported outcome measures can be leveraged to build scalable frailty scores, offering efficient cost-effective tools for monitoring outcome and guiding quality improvement in stroke care.

Purpose: COVID-19 has been extensively researched; however, the lack of standardized COVID-19 severity categorization in register-based research complicates comparison of studies. The WHO COVID-19 Clinical Progression Scale is a standardized disease severity tool for clinical data, though not adapted to data available in health registries. We aimed to develop and validate such a novel categorization with international applicability.

Methods: The WHO Clinical Progression Scale was translated to a severity index utilizing ICD-and procedure-codes from outpatient, inpatient, intensive care, and mortality registries using the adult Swedish population and SARS-CoV-2 positive-test data (January 2020 – July 2022). Cox proportional hazards were applied to determine whether increasing severity correlates with mortality in COVID-19 patients compared to the population.

Results: The WHO-Scale was translated to ten categories reflecting the increasing need for advanced care, encompassing 8,245,474 individuals including 1,981,946 SARS-CoV-2 infections. Fatal COVID-19 cases were older with more comorbidities. Those receiving mechanical ventilation and ECMO were younger with fewer comorbidities. Among survivors beyond 30 days, 90-day all-cause mortality increased with severity using category zero (no laboratory-verified SARS-CoV-2) as reference. Mortality was lowest for patients without health care adjusted for age, sex, comorbidities and socio-economic variables (adjusted hazard ratio (aHR) 1.18, 95% confidence interval (CI) 1.13–1.22). Those hospitalized >5 days had higher mortality (aHR 5.83, 5.5–6.17). Those requiring ECMO/ ECLS had the highest mortality (aHR 593.54, 317.77–1108.65).

Conclusion: The novel COVID-19 severity index associated with all-cause 90-day mortality and aligned with previous literature. This index will enable comparative studies of COVID-19, which is important for public health policies and development of clinical guidelines. This is an innovative epidemiologic tool with potential applicability in all countries with centralised health registers. The index also has the potential to be used for other infectious diseases and in real-time data for modelling predictions.

PURPOSE: Individuals with severe liver disease are more vulnerable to severe COVID-19, but the association between chronic hepatitis B virus (HBV) infection and severe COVID-19 remains unclear. This study evaluates this relationship.

METHODS: We analysed nationwide Swedish data from national databases and healthcare registers, identifying laboratory-confirmed COVID-19 cases from February 2020 to April 2021. Chronic HBV infection was classified into cases with and without cirrhosis. Multivariable logistic regression assessed the association between HBV and severe COVID-19, adjusting for demographics, comorbidities, vaccination, and socioeconomic factors.

RESULTS: Among 1,057,174 COVID-19 cases, 2,902 had chronic HBV infection, which was associated with increased risk of severe COVID-19 (adjusted odds ratio [aOR] 1.242, 95% confidence interval [CI] 1.097-1.403). This risk was significantly higher in HBV individuals with cirrhosis (aOR 2.463, CI 1.546-3.892) compared to those without cirrhosis (aOR 1.183, CI 1.039-1.343). While overall COVID-19 mortality was not significantly elevated in the HBV cohort, patients with cirrhosis showed a higher, though nonsignificant, mortality risk (aOR 2.350, CI 0.921-5.203).

CONCLUSION: This nationwide study highlights an increased risk of severe COVID-19 in individuals with chronic HBV, particularly those with cirrhosis. Geographic and socioeconomic factors further influence outcomes. These findings underscore the need to consider HBV status in COVID-19 risk assessments. Future studies should explore these associations in the context of evolving SARS-CoV-2 variants and widespread vaccination.

Rationale: The use of direct oral anticoagulants (DOACs) as stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF) has increased steadily since the introduction in 2011. In Sweden today, more patients are treated with DOACs than with warfarin. However, it is not shown that an increased proportion of DOAC prescriptions correlates to lower event rates of stroke and systemic embolism.

Objectives: This study aims to investigate whether the increased prescription of DOACs in Sweden correlates with lower event rates for all-cause stroke, systemic embolism and bleeding complications, using real-life data for the whole NVAF population.

Design: Nationwide retrospective register study.

Setting: Data were obtained from the Swedish National Patient Registry, covering patients aged 18 years or older with NVAF, between 1 January 2014, and 31 December 2017. Exposure to oral anticoagulants was determined based on pharmaceutical data, calculating treatment duration by the number of pills dispensed and the prescribed daily usage rate. Baseline characteristics and endpoints were collected from hospital administrative registers using International Classification of Diseases, 10th edition (ICD-10) codes.

Participants: All patients with NVAF were identified using ICD-10 codes during the study period. Entry criteria included having a first recorded atrial fibrillation diagnosis after 1 January 2014 or being previously diagnosed with atrial fibrillation before 2014 but still receiving care after this date.

Outcome measures: The outcomes were event rates (per 100 person-years) of ischaemic stroke, systemic embolism, all-cause stroke, major bleeding and intracranial bleeding (including haemorrhagic stroke). Event rates were calculated and compared across the study period using Cox proportional hazard models.

Results: In the total NVAF population, the proportional decrease in event rates (per 100 treatment years) in 2017 compared with 2014 was ischaemic stroke 24% (1.70-1.30), all-cause mortality 4% (9.40-9.00), all-cause stroke 24% (2.10-1.60) and all-cause stroke and systemic embolism 23% (2.20-1.70). During the same time, the proportion of major bleeding and intracranial bleeding rates, including haemorrhagic stroke, also decreased: 5% (2.00-1.90), 6% (0.68-0.64) and 17% (0.30-0.25), respectively. DOACs use increased from 4.1% to 28.3% in the total population and from 22.7% to 60.9% in newly diagnosed patients.

Conclusions: In the initial years following the introduction when DOAC uptake in the population was high, an increasing proportion of Swedish NVAF patients receiving DOACs was accompanied by lower event rates of all-cause stroke and systemic embolism, ischaemic stroke and all-cause mortality, intracranial bleeding and major bleeding, highlighting the improved risk-benefit balance of DOACs in stroke prophylaxis.

Background and Aims: Covid-19 is a multiorgan disease affecting the kidney. However, the risk of kidney injury after infection remains unknown. Therefore, this study aimed to determine the risk and time of first ever diagnosed kidney injury following Covid-19, and determine the impact of Covid-19 disease severity on this risk.

Research Questions:

• Is the risk of a first ever kidney injury increased following Covid-19 in a nationwide Swedish whole population setting?
• If so, which patients are at higher risk?

Method: The total Swedish adult population were included in the study from January 1, 2020, to July 26, 2022. Nationwide multi-registry data was used and cross-linked with Personal Identification Numbers. Data was retrieved from the Swedish Inpatient, Outpatient, Covid-19 (SmiNet), Vaccination, Intensive Care, Cancer and Cause of Death Registries. Covid-19 date (exposure) was defined as the first SARS-CoV-2 related date registered in SmiNet based on the date of symptom onset, sample date, diagnosis date or date of report. All ICD-codes (IDC9 and ICD10) used for kidney injury registered since 1987 and 2000 respectively were identified to exclude patients with previous kidney injury. Outcome was defined as all first-time events of kidney injury diagnosis (acute, non-specified and chronic) reported with ICD10 codes post Covid-19 date, during the study period. We used the Self-Controlled Case Series (SCCS) method to determine the incidence rate ratio (IRR) of kidney injury during risk periods up to 6 months after infection. In the SCCS analysis, all individuals with reported Covid-19 (exposure) and first time diagnosed kidney injury (outcome) were included. The adjusted SCCS model was used, which considers deaths in the model.

Results: Among the total 2 426 423 Covid-19 cases, there were 10 351 first kidney injury events diagnosed. In a preliminary analysis, the risk of developing kidney injury after Covid-19 was increased up to 90 days post infection with the highest IRR during the first week (day 1–7) of Covid-19 onset being 56.1 (95% CI 52.5–60). The highest risk was day 0 with nearly 200-fold increased risk, however, due to risk of selection bias (Fonseca-Rodriguez O., 2021) when including day 0, this data is excluded from the first week and should be considered with caution. The IRR was elevated for a longer time for men than for women. For women, the IRR was elevated up until 60 days post infection, compared to 90 days for men. Stratified by age groups, the IRRs were highest in the group aged 51–74 years, compared with those ≤50 years and >74 years. Individuals with higher Covid-19 disease severity were also at higher risk than those with mild infection.

Conclusion: Covid-19 is associated with an increased risk of kidney injury according to this nationwide preliminary analysis, including more than two million Covid-19 cases in Sweden. The risk of a first ever diagnosed kidney injury is elevated up to 90 days after Covid-19, which is later than previously shown. The risk was higher for men than for women and was highest for age group 51–74 years. These results highlight the importance of vaccination to prevent severe Covid-19, and if diseased by Covid-19, follow up to detect kidney injury post Covid-19.

Introduction: Little is known of the long-term prognosis of patients with acute ischaemic stroke in the absence of standard modifiable stroke risk factors (SMoRFs). In acute coronary syndromes, patients without modifiable risk factors have a higher mortality rate. We analysed data from the Swedish Stroke Register to determine survival of patients without SMoRFs following an ischaemic stroke.

Patients and methods: We identified adult patients with first-presentation acute ischaemic stroke between 2010 and 2020. Patients were considered to possess a SMoRF if they had one of: hypertension, diabetes, hyperlipidaemia, atrial fibrillation or an active smoking history. We compared mortality in patients with and without SMoRFs following first-presentation ischaemic stroke using cox regression models. We also assessed the combined endpoint death and dependency (mRS 3–6) at 3 months via logistic regression models.

Results: Of 152,588 patients with ischaemic stroke, hypertension (58.7%) and atrial fibrillation (27.3%) were the most common risk factors. 34,019 patients (22.3%) had no SMoRFs. After a first-presentation ischaemic stroke, patients without SMoRFs had a lower risk of death than patients with one or more SMoRFs (HR 0.58 [95% CI 0.57–0.59]). The absence of SMoRFs was associated with lower odds of death and dependency at 3 months in logistic regression models (OR 0·60 [95% CI 0.58–0.62]).

Conclusion: One in five patients with acute ischaemic stroke had no standard modifiable stroke risk factors. These patients have lower risk of death compared to patients with one or more SMoRFs.

Background and Aims: This study aimed to investigate the association between normal BP, (blood pressure [BP] 120–129/80–84 mmHg), and high normal BP, (BP 130–139/85–89 mmHg), compared to optimal BP, and risk of atrial fibrillation (AF).

Methods: A population-based cohort study was performed including inhabitants of Västerbotten County, Sweden, aged 30–60 years without AF at inclusion who participated in health examinations in 1988–2014. Approximately 40% of participants had ≥ 2 health examinations. The health examination included a questionnaire and measurement of BP, weight, height, and glucose. Cox regression with time-updated covariates was used to estimate the association between BP and AF risk. Restricted cubic spline analyses were performed.

Results: The cohort included 109,697 persons with 162,982 observations and a mean follow-up of 13.6 years. Incident AF was diagnosed in 5260 participants. We found an increased risk of incident AF associated with normal BP (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.01–1.27) and high normal BP (HR 1.23, 95% CI 1.10–1.38) compared to optimal BP after multivariable adjustment. Systolic BP and diastolic BP in 10 mmHg increments were associated with risk of incident AF, with HRs of 1.11 (95% CI 1.10–1.13) and 1.13 (95% CI 1.09–1.16), respectively, in multivariable models. A restricted cubic spline analysis indicated that the AF risk increased gradually with increasing systolic and diastolic BP.

Conclusion: Individuals with both normal BP and high normal BP have an increased risk of developing incident AF. The risk of AF increased gradually with increasing systolic and diastolic BP.

Aims: Doctors have an increased risk of SARS-CoV-2 infection caused by exposure to contagious patients. We aimed to identify which clinical specialities among medical doctors had the highest occupation-related risk of testing positive for SARS-CoV-2, utilizing data for all publicly employed medical doctors in Sweden.

Methods: Data regarding positive SARS-CoV-2 test results and employment for publicly employed doctors in Sweden were divided into three observation periods: 1) 1 February to 31 December 2020, 2) 1 January to 30 June 2021 and 3) 1 July 2021 to 31 March 2022. Individuals were stratified according to occupation clinic and compared with clinical occupations with little to no patient contact. The risk of testing positive for SARS-CoV-2 was estimated using Cox proportional hazards regression, with sex, age and vaccination status as covariates.

Results: The study cohort included all publicly employed doctors in Sweden: 35,028 individuals. In the first period, Infectious Disease doctors had the highest incidence of SARS-CoV-2 positive tests, with an incidence of 20.2 %, compared with 8.7 % in the reference group, and an adjusted hazard ratio of 2.5 (95% confidence interval 2.02–3.04), which decreased during period 2–3. Doctors in Geriatric Medicine had an elevated risk throughout the whole study period.

Conclusions: Our study shows an association between working in a speciality that involves caring for contagious COVID-19 patients, which raises concerns about infection control measures and routines being insufficient to prevent occupational infection in future pandemics.

Objectives: The adipocyte-derived hormone leptin has been associated with the pathogenesis of cardiovascular disease. The mechanisms underlying this association are unclear but may relate to effects on the vascular endothelium. Our aim was to explore the effects of leptin on endothelial vasomotor and fibrinolytic function in healthy volunteers and patients with coronary artery disease.

Design: The vascular effects of leptin were assessed infusing recombinant human leptin in healthy volunteers during measuring vasomotor response by venous occlusion plethysmography. Additionally, circulating levels of leptin were analysed in relation to endothelial dysfunction in patients with established coronary artery disease.

Results: In healthy male volunteers, intra-arterial infusion of recombinant human leptin (80, 800 and 8,000 ng/min; n = 10) did not affect basal forearm blood flow, plasma tissue plasminogen activator (tPA) or plasminogen activator inhibitor type 1 concentrations (all p > 0.05). However, during concomitant co-infusion with leptin (800 ng/min; n = 10), drug-induced vasodilatation was reduced (p = 0.001), and tPA activity increased (p = 0.002). In patients with coronary artery disease, those with the high plasma leptin levels had reduced drug-induced vasodilatation (p < 0.001), and increased net release of tPA antigen and activity (p < 0.001 and p = 0.03, respectively) compared to those with low levels. The study has been registered retrospectively at Clinical Trials with number NCT04374500.

Conclusion: Intrabrachial leptin infusion did not affect the basal vascular tone, whereas acute and chronic hyperleptinemia was associated with blunted vasoreactivity in healthy volunteers, and in patients with coronary artery disease.