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.

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.

Background: the majority of individuals in sweden with type 2 diabetes have theirsole health care provider in primary health care. Metformin treatment often causesgastrointestinal side-effects. Our aim was to construct and validate a questionnaireassessing gastrointestinal symptoms before and after starting metformin treatment fortype 2 diabetes.Methods: in the interaction Between Metformin and Microbiota (MeMO) study, 54participants rated six gastrointestinal symptoms at baseline and after 2 months ofmetformin treatment in a questionnaire (measured change, i.e. the difference betweenassessments at these two time points), as well as direct assessment of perceived changein symptoms after 2 months in a separate validation questionnaire (reported change, i.e.how participants themselves have perceived the change between the same two timepoints). spearman’s ρ was calculated and reported with its 95% ci.Results: 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 lowerfor nausea and vomiting, although these were numerically above 75% in agreement,likely due to few symptomatic participants overall.Conclusion: For common side-effect symptoms associated with metformin treatment,our study shows that symptom change measured as the difference between assessmentsat two different time-points was in overall agreement, validating the usability of theconstructed questionnaire for metformin side-effects.

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.

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.

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.

IntroductionStudies 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.MethodsDementia 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.ResultsOf 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.ConclusionWe 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.

Background: Orthostatic hypotension (OH) is more common in the elderly, and associated with increased mortality. However, its implications in 85-year-olds are not known.

Methods: In the prospective observational cohort study Elderly in Linköping Screening Assessment (ELSA 85), 496 individuals in Linköping, Sweden, were followed from age 85 years with cognitive assessments. Blood pressure (BP) was measured supine and after 1, 3, 5, and 10 minutes of standing. Participants with a BP fall of ≥20 mmHg systolic or ≥10 mmHg diastolic after 1 or 3 minutes were classified as classical continuous or classical transient OH depending on whether the BP fall was sustained or not, at subsequent measurements. Those with a BP fall of the same magnitude, but only after 5 or 10 minutes were classified as delayed OH.

Results: Of participants, 329 took part in BP measurements and were included. Of these, 156 (47.4%) had classical OH (113 [34.3%] continuous classical, 38 [11.6%] transient classical), and 15 (4.6%) had delayed OH. Cognitive assessments were not markedly different between groups. After 8.6 years, 195 (59.3%) of the participants had died, and delayed vs no OH was associated with twice the risk of all-cause mortality, HR 2.15 (95% CI 1.12-4.12). Transient classical OH was associated with reduced mortality, HR 0.58 (95% CI 0.33-0.99), but not after multiple adjustments, and continuous classical OH was not associated with mortality.

Conclusion: OH may have different implications for morbidity and mortality in 85-year-olds compared with younger populations.

Background

Licorice, through the effects of glycyrrhizic acid (GA), raises blood pressure (BP). The World Health Organization has suggested that 100 mg GA/d would be unlikely to cause adverse effects, but of 13 previously published studies none have been randomized and controlled and independently quantified the GA content.

Objective

Our aim was to analyze the effects on home BP of a daily licorice intake containing 100 mg GA.

Methods

Healthy volunteers were randomly assigned to start with either licorice or a control product in a nonblinded, 2 × 2 crossover study. Home BP was measured daily, and blood samples were collected at the end of each 2-wk period.

Results

There were 28 participants and no dropouts. The median age was 24.0 y (interquartile range 22.8–27.0 y). During the licorice compared with control intake period, the systolic home BP increased [mean difference: 3.1 mm Hg (95% confidence interval [CI]: 0.8, 5.4 mm Hg) compared with −0.3 mm Hg (95% CI: −1.8, 1.3 mm Hg); P = 0.018] and renin and aldosterone were suppressed [mean change: −30.0% (95% CI: −56.7%, −3.3%) compared with 15.8% (95% CI: −12.8%, 44.4%); P = 0.003; and −45.1% (95% CI: −61.5%, −28.7%) compared with 8.2% (95% CI: −14.7%, 31.1%); P <0.001, respectively]. In the quartile of participants with the most pronounced suppression of renin and aldosterone, N-terminal prohormone of brain natriuretic peptide concentration increased during the licorice compared with control period [mean change: 204.1% (95% CI: −11.6%, 419.7%) compared with 72.4% (95% CI: −52.2%, 197.1%); P = 0.016].

Conclusions

We found licorice to be more potent than previously known, with significant increases in BP, after a daily intake of only 100 mg GA. Thus, the safe limit of intake of this substance might need to be reconsidered.

Hypertension is the most common preventable cause of premature all-cause mortality, primarily from cardiovascular disease (CVD). Individuals with dysglycemia, including prediabetes and diabetes, are at increased risk. Licorice intake raises blood pressure (BP) through the effects of glycyrrhizic acid (GA), but the true limit of safe intake is uncertain. Home BP has several benefits over BP measured at a clinic, including a higher predictive value for CVD. By combining office and home BP, it is possible to diagnose masked hypertension (MH), in which home but not office BP is elevated, and white coat hypertension (WCH), in which office but not home BP is elevated. The aim of this thesis was to advance our knowledge on home BP in relation to dysglycemia, markers of CVD, and licorice intake.  

The first 3 papers used data from the Linköping cohort of the prospective Swedish CArdioPulmonary bioImage Study (SCAPIS). Study IV was a randomized controlled cross-over study. Data was obtained from questionnaires, blood samples and office and home BP measurements. In studies I-III, pulse wave velocity (PWV), coronary artery calcium score (CACS), and carotid artery plaques as markers of CVD were also included.  

In Study I, we examined 5025 men and women aged 50-64 years old for the relation between dysglycemia and home BP. Both the systolic office and home BP measurements were positively as-sociated with dysglycemia. Participants with dysglycemia vs normoglycemia more often had MH. The findings were in line with previous research and strengthened the association between dysglycemia and MH.  

In Study II, we examined the associations between MH and markers of CVD in 4122 individuals without BP-lowering treatment. Of participants, 4.2% had MH, and these were more often men and had higher BMI than those with normotension. Participants with MH also had higher odds for CACS ≥100, an as-sociation which has previously been suggested as a trend.

In Study III, we examined the relation between soluble P-se-lectin (sP-selectin) as a measure of thrombotic activity, plasma high-sensitivity C-reactive protein (hsCRP) as a measure of inflammation, and home BP in 4548 participants. Both markers were higher in each hypertension phenotype compared with sustained normotension. The quartile of participants with the highest sP-se-lectin values had higher odds for CACS ≥100 and carotid artery plaques. The association between sP-selectin and sustained hyper-tension was novel and not affected by adjustments for hsCRP.  

In Study IV, 28 healthy participants aged 18-30 years old were evaluated for the effects of a daily intake of licorice containing 100 mg of GA compared with a control product for 2 weeks. During the licorice intake period, the systolic home BP increased with 3.1 mmHg, and the suppression of serum aldosterone and plasma renin levels indicated that this was due to the licorice intake.  

In conclusion, this thesis further strengthens the idea that both home and office BP measurements have values beyond that of the other, and that home BP may be most valuable in individuals with dysglycemia and obesity, and in men. Finally, licorice may be more potent than previously known, suggesting the need for increased awareness. 

Förhöjt blodtryck (hypertoni) är den huvudsakliga orsaken till förtida död, främst genom hjärtkärlsjukdom. Flera mekanismer och riskfaktorer som kan förklara hypertoni har identifierats. Individer med förhöjt blodsocker, inklusive diabetes och dess förstadier, lö-per ökad risk för hjärtkärlsjukdom, och förhöjt blodsocker samexisterar ofta med hypertoni. Lakritsintag höjer blodtrycket genom dess beståndsdel glycyrrhizinsyra (GA), och även om både Europeiska unionen och Världshälsoorganisationen har föreslagit att ett intag av upp till 100 mg per dag sannolikt är säkert att förtära för de flesta individer, är den gränsnivån osäker.  

Jämfört med blodtryck som mäts på mottagningen av medicinskt utbildad personal har hemblodtryck flera fördelar, inklusive starkare koppling till framtida hjärtkärlsjukdom. Genom att kombinera mottagnings- och hemblodtryck går det att diagnosticera maskerad hypertoni (MH), då hemblodtrycket är förhöjt trots normalt mottagningsblodtryck, och vitrockhypertoni (WCH), då mottagningsblodtrycket men inte hemblodtrycket är förhöjd. Syftet med denna avhandling var att vidare utforska hemblodtryck i relation till förhöjt blodsocker, markörer för hjärtkärlsjukdom, och lakritsintag.  

Avhandlingens fyra arbeten baseras på två studier. I de första tre arbetena analyserades data från Linköpings-kohorten i the Swedish CArdioPulmonary bioImage Study (SCAPIS), en prospektiv studie av män och kvinnor i åldrarna 50-64 år. I det sista arbetet analyserades data från en lottad överkorsningsstudie. Data i studierna bestod av enkätsvar, blodprover, samt mottagnings- och hemblodtrycksmätningar. I studie I-III ingick även pulsvågshastighet, kalkhalt i kranskärlen vid skiktröntgen (CACS) och plack-förekomst i halspulsådrorna vid ultraljudsundersökning som markörer på hjärtkärlsjukdom.  

I det första delarbetet undersökte vi data för 5025 individer avseende blodtryck och förhöjt blodsocker. Både mottagnings- och hemblodtryck var associerat med förhöjt blodsocker. Deltagare med förhöjt blodsocker hade oftare MH jämfört med de med normalt blodsocker, och skillnaden mellan mottagnings- och hemblodtrycket var omvänt associerat med långtidsblodsocker. Fynden var i linje med tidigare forskning, och stärkte kända kopplingar mellan MH och förhöjt blodsocker. Förklaringarna till detta samband är okända, men möjliga sådana inkluderar selektiva effekter av blodtryckssänkande läkemedel hos individer med förhöjt blodsocker, samsjukligheter såsom fetma, och aktivering av det sympatiska nervsystemet.  

I det andra delarbetet analyserade vi förekomst av och associationer för MH hos 4122 individer utan pågående blodtryckssänkande läkemedelsbehandling. Av dessa hade 4.2% MH, och dessa var oftare män och hade högre BMI än de med normalt blodtryck. Deltagare med MH hade också högre pulsvågshastighet och oftare förhöjt CACS. Associationen mellan MH och markörer för hjärt-kärlsjukdom var tidigare känd och styrktes av våra resultat.  

I det tredje delarbetet undersökte vi 4548 deltagare avseende två blodprovsmarkörer: en för blodplättsaktivitet, lösligt P-selektin i blodet, och en för inflammation, högkänsligt C-reaktivt protein (hsCRP). Både P-selektin och hsCRP var högre vid hypertoni, oavsett typ, jämfört med vid normalt blodtryck. Den kvartil av deltagarna som hade högst P-selektin hade oftare WCH och hypertoni både hemma och på mottagningen, jämfört med normalt blodtryck, och oftare förhöjt CACS och plack i halspulsådrorna. Associationen mellan P-selektin och högt blodtryck både hemma och på mottagningen var inte tidigare känd, och påverkades inte av justering för hsCRP, vilket antydde att den inte enbart förklarades av inflammation.  

I det fjärde och sista delarbetet inkluderas 28 friska individer i åldrarna 18 till 30 år. I en överkorsningsstudie bad vi deltagarna att dagligen under 2 veckor inta antingen lakrits med ett innehåll av 100 mg GA eller en kontrollprodukt utan lakrits. Deltagarna undersöktes med avseende på hemblodtryck, liksom hormonnivåer i blodet. Under lakrits- jämfört med kontrollperioden steg det systoliska hemblodtrycket med 3,1 mmHg, och hormonnivåerna påverkades på ett sätt som talade för att GA påverkade blodtrycket.  

Sammanfattningsvis stärker studiernas resultat kunskapen om att blodtrycksmätning både på mottagningen och i hemmet är värdefullt både var för sig och tillsammans, och att hemblodtryck är särskilt värdefullt hos individer med förhöjt blodsocker eller övervikt, samt hos män. Slutligen visade sig små mängder lakrits påverka kroppen mer än tidigare känt, och ökad medvetenhet och bättre etikettering av lakritsprodukter kan vara befogad.