Peder Af Geijerstam

Background: Liquorice, a popular confectionary product, contains several bioactive compounds. Amongst them, glycyrrhizic acid is associated with increased blood pressure, and glabridin is associated with anti-inflammatory and glucose-lowering effects. The aim was to assess the association between short term liquorice intake at a dose known to elevate blood pressure, and markers of dysglycemia, blood lipids, high-sensitivity C-reactive protein (hsCRP), and calcium metabolism. Methods: In a 2x2 crossover study, 28 healthy adults were randomized to consume liquorice or a control product in alternating 2-week periods, with measurements of blood glycated haemoglobin A _1c as well as plasma glucose, calcium ion, parathyroid hormone, and lipids at the end of each period. Liquorice glabridin content was determined via LC-MSMS analysis. Results: The liquorice contained 0.25 ± 0.14 µg glabridin per mg. The plasma hsCRP value increased by 32.5% (95% CI −9.7 to 74.6) during the intervention period vs 311.5% (95% CI −40.8 to 663.7) during the control period, P = .045. No effects on the other markers were observed. Conclusion: Liquorice intake did not improve metabolic markers but attenuated hsCRP elevation. The potential metabolic benefits of glabridin are unlikely to outweigh the hypertensive effects when consumed as whole liquorice.

Aims: The ‘obesity paradox’ suggests lower cardiovascular risk at higher body mass index (BMI) after myocardial infarction (MI), but whether it reflects true protection or methodological bias is unclear. Methods and results: From the nationwide SWEDEHEART registry, patients hospitalized with MI from 2010 to 2021 were included. BMI at admission was modelled both as a continuous variable using restricted cubic splines and categorized into six groups, with 20 to <25 kg/m2 as reference. The primary outcome was major adverse cardiovascular events (MACE), a composite of recurrent MI, stroke, heart failure hospitalization, or cardiovascular death. Cox regression models estimated the BMI associated with lowest risk and HRs for categorical BMI groups. Adjustments included sociodemographic factors, smoking, and comorbidities not attributed to obesity. Mediation analyses assessed the roles of diabetes, hypertension, and prior cardiovascular disease. In 173 617 patients, the mean age was 71.0 years, 66.7% were men, and mean BMI was 27.1 kg/m2. During a median follow-up of 3.3 years, 36.5% experienced MACE. BMI had a U-shaped association with MACE, with the lowest risk at BMI 25.1 kg/m2. The adjusted HR (95% CI) for MACE was 0.99 (0.97–1.01) for overweight and 1.17 (1.14–1.20) for obesity class I, increasing across higher obesity classes. Excess risk was largely mediated by diabetes, hypertension, and prior cardiovascular disease. Conclusion: Obesity was associated with increased risk of MACE, partly mediated by obesity-related risk factors. The findings suggest that previously reported ‘obesity paradoxes’ may reflect differences in confounder adjustment, handling of mediators, patient populations, and survivor bias.

Introduction: Hypertension is linked to endothelial dysfunction, but causality and direction is not entirely known. The aim was to study the cross-sectional associations between home, office, and central BP and microcirculatory peak oxygen saturation (OxyP). Methods: In the observational Swedish CArdioPulmonary bioImage Study (SCAPIS) Linköping subsample, office and home BP were measured using an oscillometric device and OxyP was measured in forearm skin after a 5-min occlusion of the brachial artery. A linear regression was fitted to evaluate the mean change in OxyP per SD increase in BP. A logistic regression was fitted to evaluate the associations between BP above the median and OxyP below the median. Results: Of participants, 3,291 were included in the analyses. Per SD increase in systolic home BP, the adjusted mean (95% CI) difference in OxyP was −0.4 (−0.6 to −0.1%). In subgroup analyses, the association remained for women but not men, although the interaction by sex was not statistically significant. Also, in women but not in men, OxyP was lower in those with white coat hypertension vs. sustained normotension, i.e., mean (95% CI) 88.8 (88.2–89.4%) vs. 89.6 (89.3–90.0%), and in those with masked hypertension vs. sustained normotension, i.e., 87.5 (85.9–89.1%) vs. 89.6 (89.3–90.0%). Conclusion: Home BP, which better predicts cardiovascular disease than office BP, was inversely associated with OxyP. This correlation remained in subgroup analyses of women but not men, suggesting possible sex-dependent microcirculatory dysfunction or that masked hypertension could be a more important cardiovascular risk marker in women, despite its higher prevalence in men.

The majority of individuals in Sweden with type 2 diabetes have their sole health care provider in primary health care. Metformin treatment often causes gastrointestinal side-effects. Our aim was to construct and validate a questionnaire assessing gastrointestinal symptoms before and after starting metformin treatment for type 2 diabetes. In the Interaction Between Metformin and Microbiota (MEMO) study, 54 participants rated six gastrointestinal symptoms at baseline and after 2 months of metformin treatment in a questionnaire (measured change, i.e. the difference between assessments at these two time points), as well as direct assessment of perceived change in symptoms after 2 months in a separate validation questionnaire (reported change, i.e. how participants themselves have perceived the change between the same two time points). Spearman's ρ was calculated and reported with its 95% CI. The agreement between reported and measured change of symptoms, measured as Spearman's ρ, was above 0.4 for 4 out of 6 symptoms (poor appetite 0.60 [95% CI 0.39-0.75], loose stool or diarrhea 0.58 [95% CI 0.37-0.74], flatulence 0.45 [95% CI 0.21-0.64], and abdominal pain 0.45 [95% CI 0.20-0.65]). The agreement was lower for nausea and vomiting, although these were numerically above 75% in agreement, likely due to few symptomatic participants overall. For common side-effect symptoms associated with metformin treatment, our study shows that symptom change measured as the difference between assessments at two different time-points was in overall agreement, validating the usability of the constructed questionnaire for metformin side-effects.

Introduction: A healthy diet improves glycaemic control and reduces cardiovascular risk in type 2 diabetes (T2D). However, access to dietitians is limited. Several countries have implemented mandatory interpretive front-of-pack labelling to guide consumers towards healthier food choices, but Sweden has not. Smartphone applications may offer an alternative platform to provide such information. This study evaluates the dietary and clinical impact of a novel application providing interpretive labelling to Swedish adults with T2D. Methods and analysis: This is a fully decentralised randomised controlled trial. 900 individuals with T2D for ≥2 years who regularly shop for groceries will be recruited via general practices and community advertisements. Participants will be randomised to receive either: (1) access to the FoodSwitch mobile application plus standard written dietary advice, or (2) standard written dietary advice only. The FoodSwitch application allows users to scan barcodes on packaged foods to receive recommendations of healthier alternatives within the same category. The primary outcome is the difference in change in mean self-measured glycated haemoglobin between groups after 6 months. Secondary outcomes include differences in changes in waist circumference, body weight, quality of life, medication use, hospitalisations and all-cause mortality at 26 weeks. Exploratory outcomes include omics analyses. Recruitment is ongoing. Expected study completion on 31 December 2026. Ethics and dissemination: The trial has received ethical approval from the Swedish Ethical Review Authority (2023-06622-01, 2024-06668-02, 2024-07357-02 and 2025-01095-02) and is performed in line with World Medical Association Declaration of Helsinki and the General Data Protection Regulation. Results will be published in a peer-reviewed international journal. Trial registration number: NCT05977218 .

Introduction: Studies on the association between lipid levels and lipid-lowering treatment and the risk of dementia and/or cognitive decline (CD) have shown conflicting results and are few in individuals with type 2 diabetes (T2D). The aim was to evaluate the relationship of baseline LDL cholesterol levels and statin treatment with the development of dementia/CD in patients with T2D from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation trial. Methods: Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and CD was defined as at least a 3-point decrement in the Mini Mental State Examination score. Exposures were baseline LDL cholesterol levels, statin treatment at baseline, and statin treatment initiation during the first 18 months of follow-up. Multinomial logistic regression was used to estimate the odds ratio (OR) and 95% CI for the composite of dementia/CD. Results: Of 11,140 participants, 1827 (16.4%) developed dementia/CD over the 5-year follow up. The OR (95% CI) of dementia/CD were 1.06 (1.00–1.14) per standard deviation higher in baseline LDL cholesterol and 0.90 (0.79–1.03) for participants with vs without statin treatment. Conclusion: We observed an association between LDL levels, but not statin treatment, and incident dementia/CD. Although causality cannot be determined by our study, the results are in line with multiple randomised controlled trials. However, to understand the long-term effects of lipid levels and statin treatment on dementia/CD, studies of longer follow-up are still needed.

Objectives Investigate determinants of post-COVID-19 condition (PCC) clinic attendance among participants not hospitalised versus hospitalised during the SARS-CoV-2 infection. Design Retrospective cohort study. Setting Six population-based registers with high coverage to cover all adults residing in Stockholm County, Sweden. Participants Adults residing in Stockholm County on 31 January 2020, with a SARS-CoV-2 infection through 30 November 2022, who did not die or move out of Stockholm County within 90 days. Primary outcome measures PCC clinic attendance from 90 days after the SARS-CoV-2 test until date of death, date of moving out, or 30 November 30,2023. Results Of non-hospitalised and hospitalised participants, 737 of 464 674 (0.2%) and 433 of 23 374 (1.9%), respectively, attended a PCC clinic. A total of 75 878 (16.3%) of non-hospitalised participants and 6190 (26.5%) of hospitalised participants presented with new-onset symptoms that could indicate PCC in primary care. The strongest determinants of attendance among non-hospitalised participants were mental health disorder (adjusted risk ratio (aRR) 2.57, 95% CI 2.21 to 2.98), asthma (2.39, 1.97–2.92) and >4 PCC symptoms in 2019 (2.27, 1.60–3.24), and among hospitalised participants were >31 sick days in 2019 (1.94, 1.47–2.56), 1–30 sick days in 2019 (1.56, 1.06–2.29) and obesity (1.51, 1.19–1.93). The most common clinical presentation was fatigue (n=526, 71.4%) among non-hospitalised and dyspnoea (n=148, 34.2%) among hospitalised participants. Conclusions PCC clinic attendance characteristics differed between non-hospitalised and hospitalised participants. Distinguishing PCC from conditions with overlapping symptoms and determining the appropriate level of care may be challenging, with risk of resource displacement effects and inappropriate care.

Background: Digital tools and self-administered home blood tests offer a flexible approach to research data collection, biological sample management, and informed consent but require evaluation in relevant study settings. This study explored user experiences with a web-based digital tool for trial management, symptom reporting, and home blood testing. Methods: Forty-three middle-aged participants took part in a 12-week mixed-method study, using digital tools for trial management, self-reported health data, and self-administered glycated hemoglobin A1c home blood tests. Usability was assessed through the validated mHealth App Usability Questionnaire (MAUQ) with additional study-specific items. Every second participant completed a semi-structured interview, analyzed using qualitative content analysis. Results: The MAUQ responses (scale 1–7) indicated that digital consent (94.7% agreed), and home blood tests (100% agreed) were well-received. However, finding information on digital tools was challenging (52.9% disagreed it was easy), and participants did not perceive the tools highly effective for managing health (52.9% disagreed they were helpful). Interviews with 20 participants reinforced these findings, emphasizing motivation, support, efficient resource use, and the importance of clarity, usability, safety, and security. Conclusion: While self-administered blood tests and online consent were considered user-friendly, improvements are needed in digital tool navigation and information accessibility to enhance usability in decentralized trials, especially for participants who find them difficult or unhelpful.

Objectives: Use of snus, including tobacco and nicotine pouches, is increasing in many countries. Nicotine increases blood pressure (BP) acutely, but the long-term effects of quitting the regular use of snus pouches are unknown. The aim was to evaluate the effects of snus cessation on home BP and markers of the metabolic syndrome. Methods: Volunteers aged 18–70 years using snus daily were invited to abruptly end their snus intake and followed using home BP and metabolic measurements before and for 12 weeks after cessation. Results: Fifty volunteers were recruited. Of these, 46 (92%) attempted snus cessation and 37 (74%) did not use snus for at least 3 weeks and were included in the study. Of those included, 33 maintained snus cessation for all 12 weeks. The mean age was 38 (± 10) years and 24 (65%) were men. At week 12, the mean changes in systolic home BP was 3.7 (95% CI 1.5–5.9) mmHg, in body weight was 1.8 (95% CI 1.1–2.4) kg, and in HbA1c was 0.7 (95% CI 0.0–1.6) mmol/mol. Conclusions: Cessation of tobacco and nicotine pouches in individuals who regularly used snus negatively impacted systolic home BP, body weight and HbA1c after 12 weeks. Whether these effects would be reversed by snus re-initiation cannot be determined by this study, but our novel findings suggest that successful cessation of regular snus usage does not immediate improve these cardiovascular risk factors. We call for further research to confirm our findings and evaluate the effects over longer time frames. Clinical Trial Registry number: NCT06019910, https://clinicaltrials.gov/study/NCT06019910.

Hypertension is a risk factor for cardiovascular disease, but the evidence for treatment and blood pressure (BP) targets in the elderly is less robust. Orthostatic hypertension is a potential risk factor for cardiovascular mortality and cognitive decline. All 85-years-olds in Linköping municipality, Sweden, were invited to a prospective birth cohort study including questionnaires, cognitive testing and physical examinations, including supine and orthostatic BP measurements. Logistic regression and Cox proportional hazard models were used to assess the impact of baseline supine and orthostatic BP on cognitive decline and all-cause mortality after 5- and 7.2 years respectively. Of 650 invited 85-year-olds, 322 were included. During follow-up, 190 persons died, and 28 persons developed cognitive decline. Neither elevated supine BP nor orthostatic hypertension were associated with cognitive decline. After adjustments, elevated supine BP was not associated with mortality in all participants, but was associated with lower all-cause mortality in participants with previously diagnosed hypertension, HR 0.59 (95% CI 0.41–0.85). Orthostatic hypertension was not associated with all-cause mortality, HR 0.56 (95% CI 0.26–1.22) after multiple adjustments. In 85-year-olds with known hypertension, elevated supine BP was associated with lower all-cause mortality. Orthostatic hypertension was not associated with cognitive decline but trended towards a lower all-cause mortality.