| 1. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
- Giang, Kok Wai, 1984, et al.
(författare)
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The risk of dementia after coronary artery bypass grafting in relation to age and sex
- 2021
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:6, s. 1042-1050
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Tidskriftsartikel (refereegranskat)abstract
- Introduction We examined the long-term risk of dementia after coronary artery bypass grafting (CABG) in relation to age and sex. Methods All CABG patients in Sweden 1992-2015 (n = 111,335), and matched controls (n = 222,396) were included in a population-based study. Adjusted hazard ratios (aHR) for all-cause dementia, vascular dementia, and Alzheimer's disease were calculated. Results There was no difference in the risk for all-cause dementia between CABG patients and control subjects (aHR 0.98 [95% confidence interval 0.95 to 1.02]). CABG patients <65 years and 65 to 74 years had higher risk (aHR 1.29 [1.17-1.42] and 1.08 [1.02-1.13], respectively), and patients >= 75 years had lower risk (aHR 0.76 [0.71-0.81]). The highest risk was observed in women <65 years (aHR 1.64 [1.31-2.05]). Discussion Overall, the long-term risk for all-cause dementia does not differ between CABG patients and the general population. Younger patients have a higher risk, while older patients have a lower risk, compared to controls.
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| 3. |
- Davies, G., et al.
(författare)
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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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| 4. |
- Nielsen, Susanne, 1969, et al.
(författare)
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Socioeconomic Factors, Secondary Prevention Medication, and Long-Term Survival After Coronary Artery Bypass Grafting: A Population-Based Cohort Study From the SWEDEHEART Registry.
- 2020
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Low income and short education have been found to be independently associated with inferior survival after coronary artery bypass grafting (CABG), whereas the use of secondary prevention medications is associated with improved survival. We investigated whether underusage of secondary prevention medications contributes to the inferior long-term survival in CABG patients with a low income and short education. Methods and Results Patients who underwent CABG in Sweden between 2006 to 2015 and survived at least 6months after discharge (n=28448) were included in a population-based cohort study. Individual patient data from 5 national registries, including the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry, covering dispensing of secondary prevention medications (statins, platelet inhibitors, β-blockers, and RAAS inhibitors), socioeconomic factors, patient characteristics, comorbidity, and long-term mortaity were merged. All-cause mortality risk was estimated using multivariable Cox regression models adjusted for patient characteristics, baseline comorbidities, time-updated secondary prevention medications, and socioeconomic status. Long-term mortality was higher in patients with a low income and short education. Statins and platelet inhibitors were dispensed less often to patients with a low income, both at baseline and after 8years. The decline in dispensing over time was steeper for low-income patients. Short education was not associated with reduced dispensing of any secondary prevention medication. Use of statins (adjusted hazard ratio=0.57 [95% CI, 0.53-0.61]), RAAS inhibitors (adjusted hazard ratio=0.78 [0.73-0.84]), and platelet inhibitors (adjusted hazard ratio=0.74 [0.68-0.80]) were associated with reduced long-term mortality irrespective of socioeconomic status. Conclusions Secondary prevention medications are dispensed less often after CABG to patients with low income. Underusage of secondary prevention medications after CABG is associated with increased mortality risk independently of income and extent of education.
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| 5. |
- Silverborn, Martin, 1969, et al.
(författare)
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The performance of EuroSCORE II in CABG patients in relation to sex, age, and surgical risk: a nationwide study in 14,118 patients
- 2023
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTo determine the discriminative accuracy and calibration of EuroSCORE II in relation to age, sex, and surgical risk in a large nationwide coronary artery bypass grafting (CABG) cohort.MethodsAll 14,118 patients undergoing isolated CABG in Sweden during 2012-2017 were included. Individual patient data were taken from the SWEDEHEART registry. Patients were divided by age (< 60, 60-69, 70-79, >= 80 years), sex, and surgical risk (low: EuroSCORE < 4%, intermediate: 4-8%, high: > 8%). Discriminative accuracy was determined by the area under the receiver operating characteristic curve (AUC) and calibration by the observed/estimated (O/E) mortality ratio at 30 days.ResultsAUC and O/E ratio were 0.82 (95% CI 0.79-0.85) and 0.58 (0.50-0.66) overall, 0.82 (0.79-0.86) and 0.57 (0.48-0.66) in men, and 0.79 (0.73-0.85) and 0.60 (0.47-0.75) in women. Regarding age, discriminative accuracy was highest in patients aged 60-69 years (AUC: 0.86 [0.80-0.93]) but was satisfactory in all groups (AUC: 0.74-0.80). O/E ratio varied from 0.26 for patients > 60 years to 0.90 for patients > 80 years. Regarding surgical risk, AUC and O/E ratio were 0.63 (0.44-0.83) and 0.18 (0.09-0.30) in low-risk patients, 0.60 (0.55-0.66) and 0.57 (0.46-0.68) in intermediate-risk patients, and 0.78 (0.73-0.83) and 0.78 (0.64-0.92) in high-risk patients.ConclusionsEuroSCORE II had good discriminative accuracy independently of sex and age, but markedly overestimated mortality risk, especially in younger patients. Accuracy and calibration were better in high-risk patients than in low-risk and intermediate-risk patients.
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| 6. |
- Aljassim, Obaid, et al.
(författare)
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Inflammatory response and platelet activation after off-pump coronary artery bypass surgery.
- 2006
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Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 40:1, s. 43-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cardiac surgery induces a systemic inflammatory activation and alterations in the hemostatic cascade. The responses contribute to postoperative complications but may also have protective effects. We investigated the relationship between inflammation, hemostasis and bleeding after off-pump coronary artery bypass surgery (OPCAB). METHODS: Ten OPCAB patients were included in a prospective descriptive study. Selected markers of inflammation (IL-6, IL-8, PMN-elastase, C3a, and SC5b-9), and hemostasis (platelet count, ss-thromboglobulin, anti-thrombin, D-dimer and fibrinogen) were measured before and immediately after surgery. Postoperative bleeding was registered. RESULTS: Inflammatory variables did not alter significantly during surgery while ss-thromboglobulin concentrations increased and anti-thrombin and fibrinogen decreased. There were significant postoperative correlations between PMN-elastase and ss-thromboglobulin (r=0.82, p=0.004), between PMN-elastase and fibrinogen (r=0.69, p=0.03) and between C3a and ss-thromboglobulin (r=0.71, p=0.02). In addition, there were significant inverse correlations between postoperative bleeding and pre- and postoperative fibrinogen levels (r=-0.76, p=0.011 and r=-0.84, p=0.002 respectively), between bleeding and postoperative ss-thromboglobulin levels (r=-0.66, p=0.04) and between bleeding and postoperative PMN-elastase (r=-0.75, p=0.01). CONCLUSIONS: The results give further evidence for an association between the inflammatory response and hemostasis after cardiac surgery.
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| 7. |
- Ameur, Adam, et al.
(författare)
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SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
- 2017
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Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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| 8. |
- Björklund, Erik, et al.
(författare)
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Secondary prevention medications after coronary artery bypass grafting and long-term survival : a population-based longitudinal study from the SWEDEHEART registry.
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:17, s. 1653-1661
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To evaluate the long-term use of secondary prevention medications [statins, β-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and platelet inhibitors] after coronary artery bypass grafting (CABG) and the association between medication use and mortality.METHODS AND RESULTS: All patients who underwent isolated CABG in Sweden from 2006 to 2015 and survived at least 6 months after discharge were included (n = 28 812). Individual patient data from SWEDEHEART and other mandatory nationwide registries were merged. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between medication use and long-term mortality. Statins were dispensed to 93.9% of the patients 6 months after discharge and to 77.3% 8 years later. Corresponding figures for β-blockers were 91.0% and 76.4%, for RAAS inhibitors 72.9% and 65.9%, and for platelet inhibitors 93.0% and 79.8%. All medications were dispensed less often to patients ≥75 years. Treatment with statins [hazard ratio (HR) 0.56, 95% confidence interval (95% CI) 0.52-0.60], RAAS inhibitors (HR 0.78, 95% CI 0.73-0.84), and platelet inhibitors (HR 0.74, 95% CI 0.69-0.81) were individually associated with lower mortality risk after adjustment for age, gender, comorbidities, and use of other secondary preventive drugs (all P < 0.001). There was no association between β-blockers and mortality risk (HR 0.97, 95% CI 0.90-1.06; P = 0.54).CONCLUSION: The use of secondary prevention medications after CABG was high early after surgery but decreased significantly over time. The results of this observational study, with inherent risk of selection bias, suggest that treatment with statins, RAAS inhibitors, and platelet inhibitors is essential after CABG whereas the routine use of β-blockers may be questioned.
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| 9. |
- Cooney, Martin, 1980-, et al.
(författare)
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Impressions of Size-Changing in a Companion Robot
- 2015
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Ingår i: PhyCS 2015 – 2nd International Conference on Physiological Computing Systems, Proceedings. - : SciTePress. - 9789897580857 ; , s. 118-123
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Konferensbidrag (refereegranskat)abstract
- Physiological data such as head movements can be used to intuitively control a companion robot to perform useful tasks. We believe that some tasks such as reaching for high objects or getting out of a person’s way could be accomplished via size changes, but such motions should not seem threatening or bothersome. To gain insight into how size changes are perceived, the Think Aloud Method was used to gather typical impressions of a new robotic prototype which can expand in height or width based on a user’s head movements. The results indicate promise for such systems, also highlighting some potential pitfalls.
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| 10. |
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