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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
Salihovic, S., Dunder, L., Lind, M. & Lind, L. (2024). Assessing the performance of a targeted absolute quantification isotope dilution liquid chromatograhy tandem mass spectrometry assay versus a commercial nontargeted relative quantification assay for detection of three major perfluoroalkyls in human blood. Journal of Mass Spectrometry, 59(2), Article ID e4999.
Open this publication in new window or tab >>Assessing the performance of a targeted absolute quantification isotope dilution liquid chromatograhy tandem mass spectrometry assay versus a commercial nontargeted relative quantification assay for detection of three major perfluoroalkyls in human blood
2024 (English)In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 59, no 2, article id e4999Article in journal (Refereed) Published
Abstract [en]

Isotope dilution ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC–MS/MS) is commonly used for trace analysis of polyfluoroalkyl and perfluoroalkyl substances (PFAS) in difficult matrices. Commercial nontargeted analysis of major PFAS where relative concentrations are obtained cost effectively is rapidly emerging and is claimed to provide comparable results to that of absolute quantification using matrix matched calibration and isotope dilution UHPLC–MS/MS. However, this remains to be demonstrated on a large scale. We aimed to assess the performance of a targeted absolute quantification isotope dilution LC–MS/MS assay versus a commercial nontargeted relative quantification assay for detection of three major PFAS in human blood. We evaluated a population-based cohort of 503 individuals. Correlations were assessed using Spearman's rank correlation coefficients (rho). Precision and bias were assessed using Bland–Altman plots. For perfluorooctane sulfonic acid, the median concentrations were 5.10 ng/mL (interquartile range [IQR] 3.50–7.24 ng/mL), the two assays correlated with rho 0.83. For perfluorooctanoic acid, the median concentrations were 2.14 ng/mL (IQR 1.60–3.0 ng/mL), the two assays correlated with rho 0.92. For perfluorohexanesulfonate, the median concentrations were 5.5 ng/mL (IQR 2.50–11.61 ng/mL), the two assays correlated with rho 0.96. The Bland–Altman statistical test showed agreement of the mean difference for the majority of samples (97–98%) between the two assays. Absolute plasma concentrations of PFAS obtained using matrix matched calibration and isotope dilution UHPLC–MS/MS show agreement with relative plasma concentrations from a nontargeted commercial platform by Metabolon. We observed striking consistency between the two assays when examining the associations of the three PFAS with cholesterol, offering additional confidence in the validity of utilizing the nontargeted approach for correlations with various health phenotypes.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
cholesterol, isotope dilution, mass spectrometry, metabolon, nontargeted, PFAS, targeted
National Category
Analytical Chemistry Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-522269 (URN)10.1002/jms.4999 (DOI)001147311100001 ()38263897 (PubMedID)
Funder
Swedish Research Council Formas, 2015-756
Available from: 2024-02-05 Created: 2024-02-05 Last updated: 2024-02-05Bibliographically 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
O'Keefe, J. H., Tintle, N. L., Harris, W. S., O'Keefe, E. L., Sala-Vila, A., Attia, J., . . . Mozaffarian, D. (2024). Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies. Stroke, 55(1), 50-58
Open this publication in new window or tab >>Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies
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2024 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 55, no 1, p. 50-58Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

The effect of marine omega-3 PUFAs on risk of stroke remains unclear.

METHODS:

We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome.

RESULTS:

Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76–0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74–0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81–0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78–0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD.

CONCLUSIONS:

Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Place, publisher, year, edition, pages
American Heart Association, 2024
Keywords
atrial fibrillation, cerebrovascular disease, fish, fish oil, stroke
National Category
Public Health, Global Health, Social Medicine and Epidemiology Neurology
Identifiers
urn:nbn:se:uu:diva-520257 (URN)10.1161/STROKEAHA.123.044281 (DOI)001128650000001 ()38134264 (PubMedID)
Funder
NIH (National Institutes of Health), T32HL110837
Available from: 2024-01-11 Created: 2024-01-11 Last updated: 2024-03-15Bibliographically 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
Lind, L. & Michaëlsson, K. (2023). A detailed investigation of multiple resting cardiovascular parameters in relation to physical fitness. Clinical Physiology and Functional Imaging, 43(2), 120-127
Open this publication in new window or tab >>A detailed investigation of multiple resting cardiovascular parameters in relation to physical fitness
2023 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 43, no 2, p. 120-127Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Maximal oxygen consumption at an exercise test (VO2 -max) is a commonly used marker of physical fitness. In the present study, we aimed to find independent clinical predictors of VO2 -max by use of multiple measurements of cardiac, respiratory and vascular variables collected while resting.

METHODS: In the Prospective study of Obesity, Energy and Metabolism (POEM), 420 subjects aged 50 years were investigated regarding endothelial function, arterial compliance, heart rate variability, arterial blood flow and atherosclerosis, left ventricular structure and function, lung function, multiple blood pressure measurements, life style habits, body composition and in addition a maximal bicycle exercise test with gas exchange (VO2 and VCO2 ).

RESULTS: When VO2 -max (indexed for lean mass) was used as dependent variable and the 84 hemodynamic or metabolic variables were used as independent variables in separate sex-adjusted models, 15 variables showed associations with p<0.00064 (Bonferroni-adjusted). Eight independent variables explained 21% of the variance in VO2 -max. Current smoking and pulse wave velocity (PWV) were the two major determinants of VO2 -max (explaining each 7% and 3% of the variance; p<0.0001 and p=0.008, respectively). They were in order followed by vital capacity, fat mass, pulse pressure, and HDL-cholesterol. The relationships were inverse for all these variables, except for vital capacity and HDL.

CONCLUSION: Several metabolic, cardiac, respiratory and vascular variables measured at rest explained together with smoking 21% of the variation in VO2 -max in middle-aged individuals. Of those variables, smoking and pulse wave velocity were the most important. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
Physical fitness, VO2-max, exercise test, pulse wave velocity, smoking
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-489538 (URN)10.1111/cpf.12800 (DOI)000892669700001 ()36408896 (PubMedID)
Available from: 2022-12-01 Created: 2022-12-01 Last updated: 2023-05-16Bibliographically approved
Chen, Q. S., Bergman, O., Ziegler, L., Baldassarre, D., Veglia, F., Tremoli, E., . . . Gigante, B. (2023). A machine learning based approach to identify carotid subclinical atherosclerosis endotypes. Cardiovascular Research, 119(16), 2594-2606
Open this publication in new window or tab >>A machine learning based approach to identify carotid subclinical atherosclerosis endotypes
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2023 (English)In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 119, no 16, p. 2594-2606Article in journal (Refereed) Published
Abstract [en]

Aims To define endotypes of carotid subclinical atherosclerosis. Methods and results We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (& beta;, SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C-statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (& beta;, SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18-3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimination and reclassification in both study populations. Conclusions We report four replicable subclinical carotid atherosclerosis-endotypes associated with progression of atherosclerosis and ASCVD risk in two independent populations. Our approach based on endotypes can be applied for precision medicine in ASCVD prevention.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2023
Keywords
Atherosclerosis, Endotype, Artificial intelligence, Progression of atherosclerosis, ASCVD, Biological markers
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-523327 (URN)10.1093/cvr/cvad106 (DOI)001029952200001 ()37475157 (PubMedID)
Available from: 2024-02-21 Created: 2024-02-21 Last updated: 2024-02-21Bibliographically approved
Tschiderer, L., Seekircher, L., Izzo, R., Mancusi, C. V., Manzi, M., Baldassarre, D., . . . Willeit, P. (2023). Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 12(12)
Open this publication in new window or tab >>Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies
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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 12Article in journal (Refereed) Published
Abstract [en]

Background: The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development.

Methods and Results: We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I-2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I-2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I-2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques).

Conclusions: Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Place, publisher, year, edition, pages
Ovid Technologies (Wolters Kluwer Health), 2023
Keywords
carotid intima-media thickness, carotid plaque, individual participant data meta-analysis, prospective studies
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-508586 (URN)10.1161/JAHA.122.027657 (DOI)001015234300030 ()37301757 (PubMedID)
Available from: 2023-08-07 Created: 2023-08-07 Last updated: 2023-08-07Bibliographically approved
Ong, K. L., Marklund, M., Huang, L., Rye, K.-A., Hui, N., Pan, X.-F., . . . Wu, J. H. Y. (2023). Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts. BMJ. British Medical Journal, 380, Article ID e072909.
Open this publication in new window or tab >>Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts
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2023 (English)In: BMJ. British Medical Journal, ISSN 0959-8146, E-ISSN 0959-535X, Vol. 380, article id e072909Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived a linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis.

MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/ min/1.73 m(2). In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m(2) and <75% of baseline rate.

RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I-2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I-2=0.0%). Plant derived a linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I-2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (=60 v <60 years), estimated glomerular filtration rate (60-89 v =90 mL/min/1.73 m(2)), hypertension, diabetes, and coronary heart disease at baseline.

CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2023
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-501625 (URN)10.1136/bmj-2022-072909 (DOI)000968385900006 ()36653033 (PubMedID)
Available from: 2023-05-11 Created: 2023-05-11 Last updated: 2023-08-28Bibliographically approved
Dunder, L., Salihovic, S., Elmståhl, S., Lind, P. M. & Lind, L. (2023). Associations between per- and polyfluoroalkyl substances (PFAS) and diabetes in two population-based cohort studies from Sweden. Journal of Exposure Science and Environmental Epidemiology, 33, 748-756
Open this publication in new window or tab >>Associations between per- and polyfluoroalkyl substances (PFAS) and diabetes in two population-based cohort studies from Sweden
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2023 (English)In: Journal of Exposure Science and Environmental Epidemiology, ISSN 1559-0631, E-ISSN 1559-064X, Vol. 33, p. 748-756Article in journal (Refereed) Published
Abstract [en]

Background: Per- and polyfluoroalkyl substances (PFAS) have been suggested to contribute to the development of metabolic diseases such as obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). However, evidence from epidemiological studies remain divergent. The aim of the present study was to evaluate associations between PFAS exposure and prevalent diabetes in a cross-sectional analysis and fasting glucose in a longitudinal analysis.

Methods: In 2373 subjects aged 45-75 years from the EpiHealth study, three PFAS; perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were analyzed in plasma together with information on prevalent diabetes. Participants in the PIVUS study (n = 1016 at baseline, all aged 70 years) were followed over 10 years regarding changes in plasma levels of six PFAS; PFHxS, PFOA, PFOS, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and changes in plasma levels of fasting glucose.

Results: In the EpiHealth study, no overall associations could be observed between the levels of PFOA, PFOS or PFHxS and prevalent diabetes. However, there was a significant sex-interaction for PFOA (p = 0.02), and an inverse association could be seen between PFOA (on a SD-scale) and prevalent diabetes in women only (OR: 0.71, 95% CI: 0.52, 0.96, p-value: 0.02). This association showed a non-monotonic dose-response curve. In the PIVUS study, inverse relationships could be observed between the changes in levels (ln-transformed) of PFOA and PFUnDA vs the change in fasting glucose levels (ln-transformed) over 10 years (p = 0.04 and p = 0.02, respectively). As in EpiHealth, these inverse associations were significant only in women (PFOA: beta: -0.03, p = 0.02, PFUnDA: beta: -0.03, p = 0.03).

Impact: Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to unfavorable human health, including metabolic disorders such as obesity, diabetes and non-alcoholic fatty liver disease. However, results from in vivo, in vitro and epidemiological studies are incoherent. The aim of the present study was therefore to investigate associations between PFAS and diabetes in a cross-sectional study and glucose levels in a longitudinal study. Results show inverse associations in women only. Results also display non-monotonic dose response curves (i.e., that only low levels of PFOA are related to higher probability of prevalent diabetes). This suggests that sex differences and complex molecular mechanisms may underlie the observed findings. A better understanding of the factors and molecular mechanisms contributing to such differences is recognized as an important direction for future research.

Conclusions: PFOA was found to be inversely related to both prevalent diabetes and changes in plasma glucose levels among women only. Thus, our findings suggest there are sex differences in the inverse relationship of PFOA and type 2 diabetes and glucose levels.

Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
Perfluoroalkyl substances (PFAS), Diabetes, Cross-sectional, Longitudinal, Metabolomics
National Category
Endocrinology and Diabetes Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-517943 (URN)10.1038/s41370-023-00529-x (DOI)000958477300001 ()36964247 (PubMedID)
Funder
Uppsala University
Available from: 2023-12-18 Created: 2023-12-18 Last updated: 2023-12-18Bibliographically approved
Projects
PERSISTANT ORGANIC POLLUTANTS (POPs) AND CARDIOVASCULAR DISEASES FROM A GENDER PERSPECTIVE [2008-02214_VR]; Uppsala UniversityUSING -OMICS TECHNOLOGIES TO DISCOVER NEW PATHOPHYSIOLOGICAL PATHWAYS FOR THE FOUR MAJOR CARDIOVASCULAR DISEASES– A TRANSLATIONAL APPROACH [20200146_HLF]; Uppsala University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2335-8542

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