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Baldanzi, G., Sayols-Baixeras, S., Ekblom-Bak, E., Ekblom, Ö., Dekkers, K. F., Hammar, U., . . . Fall, T. (2024). Accelerometer-based physical activity is associated with the gut microbiota in 8416 individuals in SCAPIS. EBioMedicine, 100, Article ID 104989.
Open this publication in new window or tab >>Accelerometer-based physical activity is associated with the gut microbiota in 8416 individuals in SCAPIS
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2024 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 100, article id 104989Article in journal (Refereed) Published
Abstract [en]

Background

Previous population-based studies investigating the relationship between physical activity and the gut microbiota have relied on self-reported activity, prone to reporting bias. Here, we investigated the associations of accelerometer-based sedentary (SED), moderate-intensity (MPA), and vigorous-intensity (VPA) physical activity with the gut microbiota using cross-sectional data from the Swedish CArdioPulmonary bioImage Study.

Methods

In 8416 participants aged 50–65, time in SED, MPA, and VPA were estimated with hip-worn accelerometer. Gut microbiota was profiled using shotgun metagenomics of faecal samples. We applied multivariable regression models, adjusting for sociodemographic, lifestyle, and technical covariates, and accounted for multiple testing.

Findings

Overall, associations between time in SED and microbiota species abundance were in opposite direction to those for MPA or VPA. For example, MPA was associated with lower, while SED with higher abundance of Escherichia coli. MPA and VPA were associated with higher abundance of the butyrate-producers Faecalibacterium prausnitzii and Roseburia spp. We observed discrepancies between specific VPA and MPA associations, such as a positive association between MPA and Prevotella copri, while no association was detected for VPA. Additionally, SED, MPA and VPA were associated with the functional potential of the microbiome. For instance, MPA was associated with higher capacity for acetate synthesis and SED with lower carbohydrate degradation capacity.

Interpretation

Our findings suggest that sedentary and physical activity are associated with a similar set of gut microbiota species but in opposite directions. Furthermore, the intensity of physical activity may have specific effects on certain gut microbiota species.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Accelerometery, Gastrointestinal microbiome, Exercise, Sedentary behaviour, Epidemiology
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-522177 (URN)10.1016/j.ebiom.2024.104989 (DOI)
Available from: 2024-02-01 Created: 2024-02-01 Last updated: 2024-02-01Bibliographically approved
Gustafsson, S., Lampa, E., Jensevik, K., Butterworth, A. S., Elmståhl, S., Engström, G., . . . Sundström, J. (2024). Markers of imminent myocardial infarction. Nature Cardiovascular Research
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 2731-0590Article in journal (Refereed) Epub ahead of print
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
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-523069 (URN)10.1038/s44161-024-00422-2 (DOI)
Note

These authors contributed equally: Stefan Gustafsson, Erik Lampa

Available from: 2024-02-13 Created: 2024-02-13 Last updated: 2024-02-13Bibliographically 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, Social Medicine and Epidemiology Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-522264 (URN)10.1016/j.sste.2024.100636 (DOI)
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: 2024-02-14Bibliographically approved
Engström, G., Lampa, E., Dekkers, K., Lin, Y.-T., Ahlm, K., Ahlström, H., . . . Sundström, J. (2024). Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications. Eur J Epidemiol
Open this publication in new window or tab >>Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications
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2024 (English)In: Eur J Epidemiol, ISSN 1573-7284 Electronic 0393-2990 LinkingArticle in journal (Refereed) Published
Abstract [en]

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Keywords
Atherosclerosis Coronary heart disease Emphysema Spirometry
National Category
Health Sciences
Identifiers
urn:nbn:se:uu:diva-520136 (URN)10.1007/s10654-023-01088-z (DOI)
Note

Engstrom, Gunnar Lampa, Erik Dekkers, Koen Lin, Yi-Ting Ahlm, Kristin Ahlstrom, Hakan Alfredsson, Joakim Bergstrom, Goran Blomberg, Anders Brandberg, John Caidahl, Kenneth Cederlund, Kerstin Duvernoy, Olov Engvall, Jan E Eriksson, Maria J Fall, Tove Gigante, Bruna Gummesson, Anders Hagstrom, Emil Hamrefors, Viktor Hedner, Jan Janzon, Magnus Jernberg, Tomas Johnson, Linda Lind, Lars Lindberg, Eva Mannila, Maria Nilsson, Ulf Persson, Anders Persson, Hans Lennart Persson, Margaretha Ramnemark, Anna Rosengren, Annika Schmidt, Caroline Skoglund Larsson, Linn Skold, C Magnus Swahn, Eva Soderberg, Stefan Toren, Kjell Waldenstrom, Anders Wollmer, Per Zaigham, Suneela Ostgren, Carl Johan Sundstrom, Johan eng ERC-2018-STG-801965/ERC_/European Research Council/International Netherlands 2024/01/02 Eur J Epidemiol. 2024 Jan 2. doi: 10.1007/s10654-023-01088-z.

Available from: 2024-01-11 Created: 2024-01-11 Last updated: 2024-01-11
Sayols-Baixeras, S., Dekkers, K., Orho-Melander, M. & Fall, T. (2024). Response by Sayols-Baixeras et al to Letter Regarding Article, "Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort". [Letter to the editor]. Circulation, 149(3), Article ID 276.
Open this publication in new window or tab >>Response by Sayols-Baixeras et al to Letter Regarding Article, "Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort".
2024 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 149, no 3, article id 276Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
American Heart Association, 2024
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-522800 (URN)10.1161/CIRCULATIONAHA.123.067678 (DOI)001138942000014 ()38227717 (PubMedID)
Available from: 2024-02-09 Created: 2024-02-09 Last updated: 2024-03-08Bibliographically approved
Rydell, A., Nerpin, E., Zhou, X., Lind, L., Lindberg, E., Theorell-Haglöw, J., . . . Malinovschi, A. (2023). Cardiovascular disease-linked plasma proteins are mainly associated with lung volume. ERJ Open Research, 9(2), Article ID 00321-2022.
Open this publication in new window or tab >>Cardiovascular disease-linked plasma proteins are mainly associated with lung volume
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2023 (English)In: ERJ Open Research, E-ISSN 2312-0541, Vol. 9, no 2, article id 00321-2022Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio.

METHODS: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort.

RESULTS: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity.

CONCLUSIONS: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

Place, publisher, year, edition, pages
European Respiratory SocietyEuropean Respiratory Society (ERS), 2023
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine; Physiology
Identifiers
urn:nbn:se:uu:diva-499944 (URN)10.1183/23120541.00321-2022 (DOI)000956544900002 ()37009020 (PubMedID)
Funder
Swedish Research Council, 521-2013-2756Swedish Heart Lung Foundation, 20150427EU, European Research Council
Available from: 2023-04-05 Created: 2023-04-05 Last updated: 2024-01-15Bibliographically approved
Liu, A., Akimova, E. T., Ding, X., Jukarainen, S., Vartiainen, P., Kiiskinen, T., . . . Ganna, A. (2023). Evidence from Finland and Sweden on the relationship between early-life diseases and lifetime childlessness in men and women. Nature Human Behaviour
Open this publication in new window or tab >>Evidence from Finland and Sweden on the relationship between early-life diseases and lifetime childlessness in men and women
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2023 (English)In: Nature Human Behaviour, E-ISSN 2397-3374Article in journal (Refereed) Published
Abstract [en]

The percentage of people without children over their lifetime is approximately 25% in men and 20% in women. Individual diseases have been linked to childlessness, mostly in women, yet we lack a comprehensive picture of the effect of early-life diseases on lifetime childlessness. We examined all individuals born in 1956-1968 (men) and 1956-1973 (women) in Finland (n = 1,035,928) and Sweden (n = 1,509,092) to the completion of their reproductive lifespan in 2018. Leveraging nationwide registers, we associated sociodemographic and reproductive information with 414 diseases across 16 categories, using a population and matched-pair case-control design of siblings discordant for childlessness (71,524 full sisters and 77,622 full brothers). The strongest associations were mental-behavioural disorders (particularly among men), congenital anomalies and endocrine-nutritional-metabolic disorders (strongest among women). We identified new associations for inflammatory and autoimmune diseases. Associations were dependent on age at onset and mediated by singlehood and education. This evidence can be used to understand how disease contributes to involuntary childlessness.

Place, publisher, year, edition, pages
Nature Publishing Group, 2023
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-520137 (URN)10.1038/s41562-023-01763-x (DOI)001127090100002 ()
Funder
EU, European Research Council, 835079
Available from: 2024-01-11 Created: 2024-01-11 Last updated: 2024-02-08Bibliographically approved
Williamson, A., Norris, D. M., Yin, X., Broadaway, K. A., Moxley, A. H., Vadlamudi, S., . . . Langenberg, C. (2023). Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake. Nature Genetics, 55(6), 973-983
Open this publication in new window or tab >>Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
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2023 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 55, no 6, p. 973-983Article in journal (Refereed) Published
Abstract [en]

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-505815 (URN)10.1038/s41588-023-01408-9 (DOI)001005292100001 ()37291194 (PubMedID)
Available from: 2023-06-21 Created: 2023-06-21 Last updated: 2024-03-15Bibliographically approved
Grahnemo, L., Nethander, M., Coward, E., Gabrielsen, M. E., Sree, S., Billod, J.-M., . . . Ohlsson, C. (2023). Identification of three bacterial species associated with increased appendicular lean mass: the HUNT study.. Nature Communications, 14(1), Article ID 2250.
Open this publication in new window or tab >>Identification of three bacterial species associated with increased appendicular lean mass: the HUNT study.
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2023 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 2250Article in journal (Refereed) Published
Abstract [en]

Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species - Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum - are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.

Place, publisher, year, edition, pages
Springer NatureSpringer Nature, 2023
National Category
Orthopaedics Ecology
Identifiers
urn:nbn:se:uu:diva-501218 (URN)10.1038/s41467-023-37978-9 (DOI)001025237500001 ()37080991 (PubMedID)
Funder
Swedish Research Council, 2020-01392Lars Erik Lundberg Scholarship Foundation, LU2021-0096Novo Nordisk Foundation, NNF 190C0055250Knut and Alice Wallenberg Foundation, KAW 2015.0317
Available from: 2023-05-03 Created: 2023-05-03 Last updated: 2024-01-15Bibliographically approved
Lind, L., Fall, T., Ärnlöv, J., Elmståhl, S. & Sundström, J. (2023). Large-Scale Metabolomics and the Incidence of Cardiovascular Disease. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 12(2), Article ID e026885.
Open this publication in new window or tab >>Large-Scale Metabolomics and the Incidence of Cardiovascular Disease
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2023 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 12, no 2, article id e026885Article in journal (Refereed) Published
Abstract [en]

Background

The study aimed to show the relationship between a large number of circulating metabolites and subsequent cardiovascular disease (CVD) and subclinical markers of CVD in the general population.

Methods and Results

In 2278 individuals free from CVD in the EpiHealth study (aged 45–75 years, mean age 61 years, 50% women), 790 annotated nonxenobiotic metabolites were measured by mass spectroscopy (Metabolon). The same metabolites were measured in the PIVUS (Prospective Investigation of Vasculature in Uppsala Seniors) study (n=603, all aged 80 years, 50% women), in which cardiac and carotid artery pathologies were evaluated by ultrasound. During a median follow‐up of 8.6 years, 107 individuals experienced a CVD (fatal or nonfatal myocardial infarction, stroke, or heart failure) in EpiHealth. Using a false discovery rate of 0.05 for age‐ and sex‐adjusted analyses and P<0.05 for adjustment for traditional CVD risk factors, 37 metabolites were significantly related to incident CVD. These metabolites belonged to multiple biochemical classes, such as amino acids, lipids, and nucleotides. Top findings were dimethylglycine and N‐acetylmethionine. A lasso selection of 5 metabolites improved discrimination when added on top of traditional CVD risk factors (+4.0%, P=0.0054). Thirty‐five of the 37 metabolites were related to subclinical markers of CVD evaluated in the PIVUS study. The metabolite 1‐carboxyethyltyrosine was associated with left atrial diameter as well as inversely related to both ejection fraction and the echogenicity of the carotid artery.

Conclusions

Several metabolites were discovered to be associated with future CVD, as well as with subclinical markers of CVD. A selection of metabolites improved discrimination when added on top of CVD risk factors.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
amino acids, cardiovascular disease, epidemiology, mass spectroscopy, metabolomics
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-498756 (URN)10.1161/JAHA.122.026885 (DOI)000918066500010 ()36645074 (PubMedID)
Funder
Government of Sweden
Available from: 2023-03-20 Created: 2023-03-20 Last updated: 2023-04-03Bibliographically approved
Projects
Early life exposures: the microbiome and type 1 diabetes [2015-03477_VR]; Uppsala UniversityMolecular and microbial drivers of atherosclerosis [2019-01471_VR]; Uppsala UniversityLong-term effects of caring for a child with type 1 diabetes on parental economic and psychiatric health outcomes [2020-00372_Forte]; Uppsala UniversityCan a healthy Nordic diet counteract atherosclerosis, alter gut microbiota and be personalized to enhance diet response in coronary heart disease? [2023-02894_VR]; Uppsala UniversityLarge-scale medical image analysis for detailed studies of causes and consequences of body composition in relation to cardiovascular disease [2023-03607_VR]; Uppsala University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2071-5866

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