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  • Shah, Sonia, et al. (författare)
  • Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
  • 2020
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723 .- 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
  • Wang, R., et al. (författare)
  • Do cardiovascular risk factors explain the link between white matter hyperintensities and brain volumes in old age? : A population-based study
  • 2014
  • Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 21:8, s. 1076-1082
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: White matter hyperintensities (WMHs) and brain atrophy frequently coexist in older people. However, it is unclear whether the association between these two brain lesions is dependent on the aging process, a vascular mechanism or genetic susceptibility. It was therefore investigated whether the association between load of WMHs and brain atrophy measures is related to age, vascular risk factors (VRFs) or the APOE-epsilon 4 allele. Methods: This population-based study included 492 participants (age >= 60 years, 59.6% women) free of dementia and stroke. Data on demographics, VRFs and APOE genotypes were collected through interviews, clinical examination and laboratory tests. WMHs on magnetic resonance images were assessed using manual visual rating and automatic volumetric segmentation. Hippocampal and ventricular volumes were manually delineated, whereas total gray matter (GM) volume was measured by automatic segmentation. Data were analyzed with multivariate linear regression models. Results: More global WMHs, assessed using either a visual rating scale or a volumetric approach, were significantly associated with lower GM volume and higher ventricular volume; the associations remained significant after adjusting for age, VRFs and the APOE-epsilon 4 allele. In contrast, the association between global WMHs and hippocampal volume was no longer significant after adjusting for age, whereas adjustment for VRFs and APOE-epsilon 4 had no influential effect. Conclusion: The association of global WMHs with lower GM volume and higher ventricular volume is independent of age, VRFs and APOE-epsilon 4 allele, suggesting that the process of cerebral microvascular disease and neurodegeneration are associated independently of the normal aging process, vascular mechanisms or genetic susceptibility.
  • Qiu, C., et al. (författare)
  • Medial temporal lobe is vulnerable to vascular risk factors in men : a population based study
  • 2012
  • Ingår i: European Journal of Neurology. - 1351-5101 .- 1468-1331. ; 19:6, s. 876-883
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Vascular risk factors (VRFs) are known to cause cerebral microvascular disease, but evidence supporting an effect of VRFs on regional brain atrophy is mixed. We investigate whether an aggregation of VRFs is associated with volume of hippocampus and entorhinal cortex in elderly people living in the community. Methods: This cross-sectional study consists of 523 participants (age =60 years, 59.3% women) of the SNAC-K Study in central Stockholm, Sweden, who were free of clinical stroke and cognitive impairment. We collected data on VRFs through interviews, clinical examination and inpatient register system. Hippocampal and entorhinal cortex volume was manually measured on magnetic resonance images. Data were analysed with general linear regression models controlling for demographics and total intracranial volume. Results: In men, high total cholesterol and diabetes were significantly or marginally associated with smaller hippocampus and entorhinal cortex; when current smoking, binge alcohol drinking, high cholesterol and diabetes were aggregated, an increasing number of VRFs were significantly associated with decreasing volume of hippocampus and entorhinal cortex (P for linear trend <0.01). In women, none of individual VRFs or their aggregation was significantly associated with the volume of these brain regions, except former smoking that was significantly associated with a larger volume of these regions. Conclusions: Aggregation of VRFs is associated with reduced hippocampal and entorhinal cortex volume in apparently healthy elderly men, but not in women. This implies that in men, the medial temporal lobe is vulnerable to cardiovascular risk factors.
  • Gerritsen, L., et al. (författare)
  • The influence of negative life events on hippocampal and amygdala volumes in old age : a life-course perspective
  • 2014
  • Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 45:6, s. 1219-1228
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults.METHOD: In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning.RESULTS: Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women.CONCLUSIONS: These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.
  • Hedman, L., et al. (författare)
  • Association of Electronic Cigarette Use With Smoking Habits, Demographic Factors, and Respiratory Symptoms
  • 2018
  • Ingår i: Jama Network Open. - : American Medical Association. - 2574-3805. ; 1:3
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE There is an ongoing debate about whether electronic cigarettes (e-cigarettes) are the solution to the tobacco epidemic or a new public health threat. Large representative studies are needed to study e-cigarette use in the general population, but hardly any have been published. OBJECTIVES To estimate the prevalence of e-cigarette use and to investigate the association of e-cigarette use with smoking habits, demographic factors, and respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional, population-based study of random samples of the population, performed within the Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). The same validated questionnaire including identical questions was used in OLIN and WSAS. In 2016, OLIN and WSAS conducted postal questionnaire surveys in random samples of adults aged 20 to 75 years. In OLIN, 6519 participated (response rate, 56.4%); in WSAS, 23 753 participated (response rate, 50.1%). MAIN OUTCOMES AND MEASURES Electronic cigarette use, smoking habits, and respiratory symptoms. RESULTS Of 30 272 participants (16 325 women [53.9%]). 3897 (12.9%) were aged 20 to 29 years; 4242 (14.0%). 30 to 39 years; 5082 (16.8%). 40 to 49 years; 6052 (20.0%), 50 to 59 years; 6628 (21.9%), 60 to 69 years; and 4371(14.4%), 70 to 75 years. The number of current smokers was 3694 (12.3%), and 7305 (24.4%) were former smokers. The number of e-cigarette users was 529 (2.0%). and e-cigarette use was more common among men (275 of 12 347 [2.2%; 95% CI, 2.0%-2.5%]) than women (254 of 14 022 [1.8%; 95% CI, 1.6%-2.0%]). Among current smokers. 350 of 3566 (9.8%; 95% CI, 8.8%10.8%) used e-cigarettes compared with 79 of 6875 (1.1%; 95% CI, 0.9%-1.3%) in former smokers and 96 of 15 832 (0.6%; 95% CI, 0.5%-0.7%) in nonsmokers (P < .001). Among e-cigarette users who answered the survey question about cigarette-smoking habits (n = 525). 350 (66.7%; 95% CI, 62.7%-70.7%) were current smokers, 79 (15.0%; 95% CI, 11.9%-18.1%) were former smokers, and 96 (18.3%; 95% CI, 15.0%-21.6%) were nonsmokers (P < .001 for trend). In a regression analysis, e-cigarette use was associated with male sex (odds ratio [OR], 1.35; 95% CI. 1.12-1.62); age groups 20 to 29 years (OR. 2.77; 95% CI, 1.90-4.05), 30 to 39 years (OR, 2.27; 95% CI, 1.53-3.36), 40 to 49 years (OR, 1.65; 95% CI, 1.11-2.44). and 50 to 59 years (OR, 1.47; 95% CI, 1.01-2.12); educational level at primary school (OR, 1.99; 95% CI, 1.51-2.64) and upper secondary school (OR, 1.57; 95% CI, 1.25-1.96); former smoking (OR. 2.37; 95% CI, 1.73-3.24); and current smoking (OR. 18.10; 95% CI, 14.19-23.09). All respiratory symptoms were most common among dual users and former smokers and nonsmokers who used e-cigarettes. CONCLUSIONS AND RELEVANCE Use of e-cigarettes was most common among smokers, and dual users had the highest prevalence of respiratory symptoms. On a population level, this study indicates that the present use of e-cigarettes does not adequately serve as a smoking cessation tool.
  • Jakobsson, Martin, 1966-, et al. (författare)
  • An Arctic Ocean ice shelf during MIS 6 constrained by new geophysical and geological data
  • 2010
  • Ingår i: Quaternary Science Reviews. - 0277-3791 .- 1873-457X. ; 29:25-26, s. 3505-3517
  • Tidskriftsartikel (refereegranskat)abstract
    • The hypothesis of floating ice shelves covering the Arctic Ocean during glacial periods was developed in the 1970s. In its most extreme form, this theory involved a 1000 m thick continuous ice shelf covering the Arctic Ocean during Quaternary glacial maxima including the Last Glacial Maximum (LGM). While recent observations clearly demonstrate deep ice grounding events in the central Arctic Ocean, the ice shelf hypothesis has been difficult to evaluate due to a lack of information from key areas with severe sea ice conditions. Here we present new data from previously inaccessible, unmapped areas that constrain the spatial extent and timing of marine ice sheets during past glacials. These data include multibeam swath bathymetry and subbottom profiles portraying glaciogenic features on the Chukchi Borderland, southern Lomonosov Ridge north of Greenland, Morris Jesup Rise, and Yermak Plateau. Sediment cores from the mapped areas provide age constraints on the glaciogenic features. Combining these new geophysical and geological data with earlier results suggests that an especially extensive marine ice sheet complex, including an ice shelf, existed in the Amerasian Arctic Ocean during Marine Isotope Stage (MIS) 6. From a conceptual oceanographic model we speculate that the cold halocline of the Polar Surface Water may have extended to deeper water depths during MIS 6 inhibiting the warm Atlantic water from reaching the Amerasian Arctic Ocean and, thus, creating favorable conditions for ice shelf development. The hypothesis of a continuous 1000 m thick ice shelf is rejected because our mapping results show that several areas in the central Arctic Ocean substantially shallower than 1000 m water depth are free from glacial influence on the seafloor.
  • Vikdahl, M., et al. (författare)
  • Cardiovascular risk factors and the risk of Parkinson's disease
  • 2015
  • Ingår i: European Journal of Clinical Nutrition. - 0954-3007 .- 1476-5640. ; 69:6, s. 729-733
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/OBJECTIVES: The objective of this study was to investigate whether serum triglycerides (S-TG), cholesterol, blood pressure and waist/height ratio are risk factors for Parkinson's disease (PD).SUBJECTS AND METHODS: A population-based sample within the Northern Sweden Health and Disease Study (NSHDS) was used in this study (n = 101 790 subjects). Cases with PD were identified prospectively in a community-based study of idiopathic Parkinsonism in the period 2004-2009 in the county of Vasterbotten in northern Sweden. The case database obtained was crosslinked to the NSHDS. Eighty-four of 147 patients with PD had visited the primary health care 2-8 years before diagnosis for participation in the NSHDS. For each case, four referents from the NSHDS population were selected, matched for sex, age, year of health survey, subcohort and geographic area.RESULTS: Cases had lower mean S-TG levels (P = 0.007). After stratification for sex, the lower S-TG remained significant for men (P = 0.006) but not for women (P = 0.450), and these were confirmed by the conditional logistic regression for all cases, none adjusted (hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.42, 0.99) and after adjusting for age, body mass index (BMI) and physical activity (HR: 0.61; 95% CI: 0.39, 0.96). Systolic blood pressure (SBP) was negatively associated with PD risk after adjustments for age, BMI and physical activity (HR: 0.98; 95% CI: 0.97-0.99). Smoking and former smoking were associated with a reduced risk for PD.CONCLUSIONS: We found lower S-TG and SBP 2-8 years before a diagnosis of PD. Smoking was confirmed to be negatively associated with PD, whereas recreational activity indicates a risk for women.
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