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- Grut, Viktor, 1980-
(author)
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Exposures associated with multiple sclerosis development : presymptomatic case-control studies
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Background: Multiple sclerosis (MS) is a chronic immune-mediated disease affecting the central nervous system. The current view is that MS is caused by a complex interplay of several environmental factors, eliciting an immune reaction in genetically susceptible individuals. Most previous studies of MS aetiology were retrospective, conferring the risk of reverse causation or recall bias. Few studies have been performed on data collected before the onset of the disease. The objective of this project was to identify risk factors for MS by analysing markers of exposure in samples collected before the clinical onset of MS.Method: A series of nested case-control studies were performed by cross-linking Swedish MS registries with Swedish biobanks, thereby identifying serum or plasma samples from up to 837 cases who later developed MS. For each case, up to two matched controls were selected. The following environmental risk factors were assessed: Antibodies against herpesviruses Epstein-Barr virus (EBV), Human herpesvirus 6A (HHV-6A) and Cytomegalovirus (CMV); Free Vitamin D3 Index and Vitamin D Binding Protein (DBP); and C-reactive Protein (CRP). Early signs of neural injury were assessed by measuring the concentration of neurofilament light chain in serum (sNfL). The associations between the environmental factors and future development of MS were analysed with conditional logistic regression, calculating odds ratios (OR) with 95% confidence intervals (CI). Interactions were analysed on the multiplicative and additive scales. The temporal relation of HHV-6A serostatus and axonal injury was analysed with locally estimated scatterplot smoothing regression.Results: Serological evidence of CMV infection was associated with a lower risk of MS development (OR = 0.70, 95% CI 0.56–0.88). Antagonistic interactions were observed between serological signs of CMV, HHV-6A, and EBV infection. Antibodies against HHV-6A were associated with a higher level of sNfL. In MS cases, increasing levels of HHV-6A antibodies were detected several years before increasing sNfL. Among young individuals, high levels of Free Vitamin D3 Index were associated with a lower MS risk (OR = 0.37, 95% CI 0.15–0.91). In older individuals, high levels of DBP were associated with a lower risk of developing MS (OR = 0.36, 95% CI 0.15–0.85). Elevated levels of CRP were not associated with MS risk.Conclusions: These results strengthen the evidence for HHV-6A and EBV in MS aetiology. They also support the hypothesis that CMV infection and a high level of free Vitamin D3 during childhood and adolescence are associated with a lower risk of MS later in life.
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| 2. |
- Hvidtfeldt, Ulla A., et al.
(author)
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Alcohol Intake and Risk of Coronary Heart Disease in Younger, Middle-Aged, and Older Adults
- 2010
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In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 121:14, s. 1589-1597
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Journal article (peer-reviewed)abstract
- Background-Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease. This protective effect of alcohol, however, may be confined to middle-aged or older individuals. Coronary heart disease incidence is low in men <40 years of age and in women <50 years of age; for this reason, study cohorts rarely have the power to investigate the effects of alcohol on coronary heart disease risk in younger adults. This study examined whether the beneficial effect of alcohol on coronary heart disease depends on age. Methods and Results-In this pooled analysis of 8 prospective studies from North America and Europe including 192 067 women and 74 919 men free of cardiovascular diseases, diabetes, and cancers at baseline, average daily alcohol intake was assessed at baseline with a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups; hazard ratios among moderately drinking men (5.0 to 29.9 g/d) 39 to 50, 50 to 59, and >= 60 years of age were 0.58 (95% confidence interval [CI], 0.36 to 0.93), 0.72 (95% CI, 0.60 to 0.86), and 0.85 (95% CI, 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference between abstainers and moderate consumers in younger adults (incidence rate difference, 45 per 100 000; 90% CI, 8 to 84) than in middle-aged (incidence rate difference, 64 per 100 000; 90% CI, 24 to 102) and older (incidence rate difference, 89 per 100 000; 90% CI, 44 to 140) adults. Similar results were observed in women. Conclusion-Alcohol is also associated with a decreased risk of coronary heart disease in younger adults; however, the absolute risk was small compared with middle-aged and older adults. (Circulation. 2010; 121: 1589-1597.)
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| 3. |
- Jakobsen, Marianne U, et al.
(author)
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Major types of dietary fat and risk of coronary heart disease : a pooled analysis of 11 cohort studies.
- 2009
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 89:5, s. 1425-1432
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Journal article (peer-reviewed)abstract
- BACKGROUND: Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance. OBJECTIVE: We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. DESIGN: This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. RESULTS: During 4-10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. CONCLUSION: The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes.
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| 6. |
- Simon, K. Claire, et al.
(author)
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Age at Epstein-Barr virus infection and Epstein-Barr virus nuclear antigen-1 antibodies in Swedish children
- 2012
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In: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 1:3, s. 136-138
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Journal article (peer-reviewed)abstract
- There is strong evidence supporting a role for Epstein-Barr virus (EBV) in the etiopathogenesis of multiple sclerosis (MS). Because of the strong association between antibody (Ab) titer against EBV nuclear antigen 1 (EBNA1) and late age at EBV infection, manifested as infectious mononucleosis (IM), and MS risk, we sought to determine whether age at primary EBV infection was associated with subsequent anti-EBNA1 Ab titer in a longitudinal study of Swedish children with EBV seropositivity and anti-EBNA1 Ab titers measured at ages 2, 5, and 10.
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| 7. |
- Tessier, Anne Julie, et al.
(author)
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Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies
- 2024
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In: Med. - 2666-6359 .- 2666-6340. ; 5:3, s. 224-238.e5
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Journal article (peer-reviewed)abstract
- Background: A healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity. Methods: In four large cohorts with 13,056 individuals and 28-year follow-up, we assessed five healthy lifestyle factors, used liquid chromatography mass spectrometry to profile plasma metabolites, and ascertained deaths with death certificates. The unique healthy lifestyle metabolomic signature was identified using an elastic regression. Multivariable Cox regressions were used to assess associations of the signature with mortality and longevity. Findings: The identified healthy lifestyle metabolomic signature was reflective of lipid metabolism pathways. Shorter and more saturated triacylglycerol and diacylglycerol metabolite sets were inversely associated with the healthy lifestyle score, whereas cholesteryl ester and phosphatidylcholine plasmalogen sets were positively associated. Participants with a higher healthy lifestyle metabolomic signature had a 17% lower risk of all-cause mortality, 19% for cardiovascular disease mortality, and 17% for cancer mortality and were 25% more likely to reach longevity. The healthy lifestyle metabolomic signature explained 38% of the association between the self-reported healthy lifestyle score and total mortality risk and 49% of the association with longevity. Conclusions: This study identifies a metabolomic signature that measures adherence to a healthy lifestyle and shows prediction of total and cause-specific mortality and longevity. Funding: This work was funded by the NIH, CIHR, AHA, Novo Nordisk Foundation, and SciLifeLab.
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