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Title [sv]
Molekyler och mikrober som påskyndar åderförkalkning
Title [en]
Molecular and microbial drivers of atherosclerosis
Abstract [en]
This proposal builds on the recent completion of the world-unique cardiovascular imaging study Swedish CArdio Pulmonary Bio Image Study (SCAPIS) and recent technological break-troughs in analytical chemistry and sequencing technology. The overall aim of the project is to identify novel targets for early intervention of cardiovascular disease by identifying circulating metabolites that contribute to atherosclerosis and their potential origin in the intestinal microbiota.We will screen ~1,000 metabolites in 5,000 individuals from the SCAPIS-Uppsala cohort for links with atherosclerosis with replication in 3,000 individuals from the SCAPIS-Malmö cohort; and assessment of the longitudinal development in a subset of SCAPIS-Umeå/VHS cohort (n=400); and with incident myocardial infarction (~900 events) and ischemic stroke (~500 events) in SCAPIS, MIMI and SIMPLER to identify metabolites linked to different stages of atherosclerosisWe will use machine learning to identify the intestinal microbiota components that are associated with these atherosclerosis-linked metabolites in 8,000 individualsWe will apply network Mendelian Randomization methods based on novel genetic instruments and metabolite perturbation in mice to map the causal network of microbiota, metabolites and atherosclerosis and prioritise candidateThe anticipated outcome of this project will be a set of candidate targets for early intervention of cardiovascular disease, which I plan to take forward to drug development.
Publications (4 of 4) Show all publications
Arage, G., Dekkers, K. F., Raso, L. M., Hammar, U., Ericson, U., Larsson, S. C., . . . Ahmad, S. (2025). Response to letter to the editor regarding: "Plasma metabolite profiles of meat intake and their association with cardiovascular disease risk: A population-based study in Swedish cohorts" by Arage et al., Metabolism. 2025 Jul;168:156188 [Letter to the editor]. Metabolism: Clinical and Experimental, 171, Article ID 156309.
Open this publication in new window or tab >>Response to letter to the editor regarding: "Plasma metabolite profiles of meat intake and their association with cardiovascular disease risk: A population-based study in Swedish cohorts" by Arage et al., Metabolism. 2025 Jul;168:156188
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2025 (English)In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 171, article id 156309Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2025
National Category
Cardiology and Cardiovascular Disease Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-570144 (URN)10.1016/j.metabol.2025.156309 (DOI)001587568800002 ()40449615 (PubMedID)2-s2.0-105008467926 (Scopus ID)
Funder
EU, European Research Council, ERC-STG-2018-801965EU, European Research Council, ERC-CoG-2014-649021Swedish Research Council, VR 2019-00977Swedish Research Council, 2019-01471Swedish Research Council, 2018-02784Swedish Research Council, 2019-01015Swedish Research Council, 2020-00243Swedish Research Council, 2019-01236Swedish Research Council, 2022-01460Swedish Research Council, 2022-06725Swedish Heart Lung Foundation, 2023-0687Swedish Heart Lung Foundation, 20200711Swedish Heart Lung Foundation, 20180343Swedish Heart Lung Foundation, 20200173Swedish Cancer SocietySwedish Research Council Formas, 2020-00989Region StockholmKnut and Alice Wallenberg FoundationVinnovaKarolinska Institute
Available from: 2025-10-22 Created: 2025-10-22 Last updated: 2025-10-22Bibliographically approved
Graells, T., Lin, Y.-T., Ahmad, S., Fall, T. & Ärnlöv, J. (2025). The urinary microbiome in association with diabetes and diabetic kidney disease: A systematic review. PLOS ONE, 20(1), Article ID e0317960.
Open this publication in new window or tab >>The urinary microbiome in association with diabetes and diabetic kidney disease: A systematic review
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2025 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 20, no 1, article id e0317960Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The urinary microbiome, or urobiome, is a novel area of research that has been gaining attention recently, as urine was thought to be sterile for years. There is limited information about the composition of the urobiome in health and disease. The urobiome may be affected by several factors and diseases such as diabetes, a disease that often leads to kidney damage. Thus, we need to understand the role of the urobiome to assess and monitor kidney disease related to diabetes over time.

METHODS: We conducted a systematic review to summarize knowledge about the urobiome in association with diabetes mellitus and diabetic kidney disease. The search was conducted in several electronic databases until November 2024.

RESULTS: Eighteen studies were selected including cross-sectional case-control studies, cross-sectional surveys and one prospective longitudinal study. In total, the urobiome of 1,571 people was sequenced, of which 662 people had diabetes, and of these 36 had confirmed diabetic kidney disease; 609 were healthy individuals, 179 had prediabetes or were at risk of type 2 diabetes mellitus and 121 did not have diabetes but had other comorbidities. Eight studies analysed data from females, one was focused on male data, and the other nine had mixed female-male data. Most of the studies had a small sample size, used voided midstream urine, and used 16S rRNA sequencing.

CONCLUSION: This systematic review summarizes trends seen throughout published data available to have a first baseline knowledge of the urinary microbiome, and its microbiota, in association with diabetes including the decreased richness and α-diversity in urinary microbiota in individuals with diabetes compared to healthy controls and the decreased α-diversity with the evolution of kidney disease independently of the cause.

Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2025
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-551069 (URN)10.1371/journal.pone.0317960 (DOI)001412818500029 ()39888908 (PubMedID)2-s2.0-85216903360 (Scopus ID)
Funder
Swedish Research Council, 2019-01015Swedish Research Council, 2019-01471Swedish Research Council, 2020-0243Swedish Heart Lung Foundation, 2021-0357Swedish Heart Lung Foundation, 2023-0687Swedish Heart Lung Foundation, 2024-0486Swedish Research Council Formas, 2020-00989Swedish Research Council, 2022-01460
Available from: 2025-02-21 Created: 2025-02-21 Last updated: 2025-04-10Bibliographically approved
Gustafsson, S., Lampa, E., Jensevik Eriksson, K., Butterworth, A. S., Elmståhl, S., Engström, G., . . . Sundström, J. (2024). Markers of imminent myocardial infarction. Nature Cardiovascular Research, 3(2), 130-139
Open this publication in new window or tab >>Markers of imminent myocardial infarction
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2024 (English)In: Nature Cardiovascular Research, E-ISSN 2731-0590, Vol. 3, no 2, p. 130-139Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Cardiology and Cardiovascular Disease
Identifiers
urn:nbn:se:uu:diva-523069 (URN)10.1038/s44161-024-00422-2 (DOI)001160066800002 ()39196201 (PubMedID)
Funder
Uppsala UniversityEU, FP7, Seventh Framework Programme, 313010European Regional Development Fund (ERDF), 2014-2020.4.01.15-0012European Commission, HEALTH-F2-2012-279233EU, European Research Council, 268834Swedish Cancer SocietySwedish Research Council, 2019-01471Region SkåneRegion VästerbottenSwedish Heart Lung Foundation, 20190505Knut and Alice Wallenberg FoundationVinnovaEU, European Research Council, 801965AFA Insurance, 160266Swedish Research Council, 2016-01065Swedish Heart Lung Foundation, 20160734Swedish National Infrastructure for Computing (SNIC), sens2019006Swedish National Infrastructure for Computing (SNIC), sens2020005UPPMAXSwedish Research Council, 2018-05973
Note

These authors contributed equally: Stefan Gustafsson, Erik Lampa

Available from: 2024-02-13 Created: 2024-02-13 Last updated: 2025-02-10Bibliographically approved
van Zoest, V., Lindberg, K., Varotsis, G., Osei, F. B. & Fall, T. (2024). Predicting COVID-19 hospitalizations: The importance of healthcare hotlines, test positivity rates and vaccination coverage. Spatial and Spatio-temporal Epidemiology, 48, Article ID 100636.
Open this publication in new window or tab >>Predicting COVID-19 hospitalizations: The importance of healthcare hotlines, test positivity rates and vaccination coverage
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2024 (English)In: Spatial and Spatio-temporal Epidemiology, ISSN 1877-5845, E-ISSN 1877-5853, Vol. 48, article id 100636Article in journal (Refereed) Published
Abstract [en]

In this study, we developed a negative binomial regression model for one-week ahead spatio-temporal predictions of the number of COVID-19 hospitalizations in Uppsala County, Sweden. Our model utilized weekly aggregated data on testing, vaccination, and calls to the national healthcare hotline. Variable importance analysis revealed that calls to the national healthcare hotline were the most important contributor to prediction performance when predicting COVID-19 hospitalizations. Our results support the importance of early testing, systematic registration of test results, and the value of healthcare hotline data in predicting hospitalizations. The proposed models may be applied to studies modeling hospitalizations of other viral respiratory infections in space and time assuming count data are overdispersed. Our suggested variable importance analysis enables the calculation of the effects on the predictive performance of each covariate. This can inform decisions about which types of data should be prioritized, thereby facilitating the allocation of healthcare resources.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
COVID-19, Negative binomial regression, Spatio-temporal modeling, Time series, Prediction
National Category
Public Health, Global Health and Social Medicine Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-522264 (URN)10.1016/j.sste.2024.100636 (DOI)001175332600001 ()
Funder
EU, European Research Council, ERC-2018-STG 801965Vinnova, 2020-03173Swedish Heart Lung Foundation, 2019-0505Swedish Research Council, 2019-01471
Available from: 2024-02-02 Created: 2024-02-02 Last updated: 2025-02-20Bibliographically approved
Principal InvestigatorFall, Tove
Coordinating organisation
Uppsala University
Funder
Period
2020-01-01 - 2023-12-31
National Category
Cardiac and Cardiovascular SystemsPublic Health, Global Health, Social Medicine and Epidemiology
Identifiers
DiVA, id: project:6596Project, id: 2019-01471_VR