| 1. |
- Larsson, David, 1986, et al.
(författare)
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Cardiovascular risk factor assessment in late-onset seizures: A study protocol to assess the value of structured intervention
- 2024
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Ingår i: EPILEPSIA OPEN. - 2470-9239. ; 9:4, s. 1611-1617
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveA growing body of evidence suggests patients with late-onset seizures are at an increased risk of stroke, but the potential for reducing cardiovascular morbidity through risk factor screening and management is unknown. We aim to determine whether individuals with new-onset unprovoked seizures after middle age should undergo vascular risk assessment. The long follow-up needed to assess stroke risk and the known benefit of vascular risk factor modification make a standard RCT logistically and ethically challenging. Instead, we propose and have developed a protocol for a cluster project assessing the effect of vascular risk factor screening in an intervention trial as well as a cohort study.MethodsParticipating neurology clinics will implement standard cardiovascular risk factor assessment into the routine evaluation for individuals aged >= 50 years attending their first specialized consultation after an unprovoked seizure, excluding those with progressive brain disease. The project has two interlinked components: a prospective single group trial, in which risk factor assessment is performed and subsequent management is followed for one year; and a register-based cohort study examining the long-term effects of the intervention on a system level by comparing patients attending initial consultations in the 2 years after start of the study, with patients seen in the four preceding years at the same clinics.AnalysisThe primary outcome of the intervention trial is the proportion of patients receiving subsequent pharmacological treatment. The primary outcome of the cohort study is the incidence of acute stroke in the Swedish Stroke Register.Ethics and DisseminationSwedish Ethical Review Authority approval (which is valid for 2 years only) will be sought when funding is obtained. The results will be disseminated through peer-reviewed scientific publications.Registration DetailsThe study will be registered at .Plain Language SummaryA first seizure in a middle-aged or older person indicates a higher risk of stroke. It is not known whether investigating and treating blood pressure, blood cholesterol, or similar risk factors after a first seizure is an effective way to prevent stroke. A traditional clinical study would need too many patients and it would be unethical not to treat the control group. We have designed a study in which participating neurology departments change their practice to test and treat vascular risk factors. Patients are then compared to historic controls using registered data.
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| 2. |
- Sundelöf, Johan, et al.
(författare)
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Cystatin C Levels are Positively Correlated with both Aβ42 and Tau Levels in Cerebrospinal Fluid in Persons with Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls
- 2010
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 21:2, s. 471-478
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Tidskriftsartikel (refereegranskat)abstract
- Cystatin C is suggested to be involved in neurodegeneration and the development of Alzheimer's disease (AD) by binding to soluble amyloid-beta (Abeta) peptides. Studies of cystatin C levels in cerebrospinal fluid (CSF) in relation to risk of AD are conflicting and relations between cystatin C, Abeta42, and tau levels in CSF in AD, mild cognitive impairment (MCI), and healthy controls are unknown. The objective of this study was to investigate cystatin C, Abeta42, and tau levels in CSF in AD, MCI, and controls. As a secondary aim, the relationships between cystatin C, Abeta42, and tau levels across disease groups were investigated. Cystatin C, Abeta42, total tau, and phosphorylated tau levels in CSF were analyzed by turbidimetry (cystatin C) and xMAP Luminex technology (Abeta and tau) in persons with AD (n=101), MCI (n=84), and healthy control subjects (n=28). Mean cystatin C levels were similar in cases of AD (5.6 mumol/L +/- 1.7), MCI (5.4 mumol/L +/- 1.48), and controls (5.6 mumol/L +/- 1.6). However, CSF cystatin C levels were strongly and positively correlated with total tau and phosphorylated tau levels (r=0.61-0.81, p< 0.0001) and Abeta42 (r=0.35-0.65, p< 0.001) independent of age, gender, and APOE genotype. Mean CSF cystatin C levels did not differ between patients with AD and MCI and healthy controls. Interestingly, cystatin C levels were positively correlated with both tau and Abeta42 levels in CSF independent of age, gender, and APOE genotype.
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| 3. |
- Waagaard, Lovisa, et al.
(författare)
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Body mass index and weight gain in pregnancy and cardiovascular health in middle age: A cohort study
- 2024
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Ingår i: BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY. - : John Wiley & Sons. - 1470-0328 .- 1471-0528. ; 131:8, s. 1136-1145
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine associations between body mass index (BMI) in early pregnancy and gestational weight gain (GWG) with cardiovascular health in middle age using the 'Life's Essential 8' (LE8) concept of the American Heart Association (AHA).Design: Population-based cohort study.Setting: Swedish CardioPulmonary bioImage Study (SCAPIS).Population: A total of 8871 women from SCAPIS were included.Methods: Information on cardiovascular health in middle age was collected from SCAPIS and linked to pregnancy weight data obtained from the Swedish Medical Birth Register, with an average follow-up time of 24.5 years. An LE8 score between 0 and 100 was determined, where a score under 60 points was defined as poor cardiovascular health. Binary logistic regression and restricted cubic splines were used.Main outcome measures: Cardiovascular health according to LE8 in middle age.Results: The odds of having poor cardiovascular health in middle age were significantly higher in women who had overweight (adjusted odds ratio, aOR 3.30, 95% CI 2.82-3.88) or obesity (aOR 7.63, 95% CI 5.86-9.94), compared with women classified as being of normal weight in pregnancy. Higher odds were also found for excessive GWG (aOR 1.31, 95% CI 1.09-1.57), compared with women who gained weight within the recommendations. Conclusions: A high BMI in early pregnancy and excessive GWG were associated with greater odds of poor cardiovascular health in middle age. Although further studies are needed, our results highlight pregnancy as an important period to support long-term cardiovascular health.
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| 5. |
- Baron, Tomasz, et al.
(författare)
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Impact on Long-Term Mortality of Presence of Obstructive Coronary Artery Disease and Classification of Myocardial Infarction
- 2016
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Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 129:4, s. 398-406
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In contrast to the associated-with-thromboembolic-event type 1 myocardial infarction, type 2 myocardial infarction is caused by acute imbalance between oxygen supply and demand of myocardium. Type 2 myocardial infarction may be present in patients with or without obstructive coronary artery disease, but knowledge about patient characteristics, treatments, and outcome in relation to coronary artery status is lacking. We aimed to compare background characteristics, triggering mechanisms, treatment, and long-term prognosis in a large real-life cohort of patients with type 1 and type 2 myocardial infarction with and without obstructive coronary artery disease.METHODS: All 41,817 consecutive patients with type 1 and type 2 myocardial infarction registered in the Swedish myocardial infarction registry (SWEDEHEART) who underwent coronary angiography between January 1, 2011 and December 31, 2013, with the last follow-up on December 31, 2014, were studied.RESULTS: In 92.8% of 40,501 patients classified as type 1 and in 52.5% of patients classified as type 2 myocardial infarction, presence of an obstructive coronary artery disease could be shown. Within the patients with obstructive coronary artery disease, those with type 2 myocardial infarction were older, and had more comorbidities and smaller necrosis as compared with type 1 myocardial infarction. In contrast, there was almost no difference in risk profile and extent of myocardial infarction between type 1 and type 2 myocardial infarction patients with nonobstructive coronary artery stenosis. The crude long-term mortality was higher in type 2 as compared with type 1 myocardial infarction with obstructive coronary artery disease (hazard ratio [HR] 1.72; 95% confidence interval [CI], 1.45-2.03), but was lower after adjustment (HR 0.76; 95% CI, 0.61-0.94). In myocardial infarction patients with nonobstructive coronary artery stenosis, the mortality risk was similar regardless of the clinical myocardial infarction type (crude HR 1.14; 95% CI, 0.84-1.55; adjusted HR 0.82; 95% CI, 0.52-1.29).CONCLUSIONS: The substantial differences in risk factors, treatment, and outcome in patients with type 1 and type 2 myocardial infarction with obstructive coronary artery disease supports the relevance of the division between type 1 and type 2 in this population. On the contrary, in patients with nonobstructive coronary artery stenosis, irrespective of the clinical type, a similar risk profile, extent of necrosis, and longterm prognosis were observed, indicating that distinction between type 1 and type 2 myocardial infarction in these patients seems to be inappropriate.
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| 6. |
- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 9. |
- Klaric, Lucija, et al.
(författare)
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Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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| 10. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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