| 1. |
- Andersson, Jessika, et al.
(författare)
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The carotid artery plaque size and echogenicity are related to different cardiovascular risk factors in the elderly : the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study
- 2009
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Ingår i: Lipids. - : Springer. - 0024-4201 .- 1558-9307. ; 44:5, s. 397-403
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Tidskriftsartikel (refereegranskat)abstract
- Carotid plaques can be characterised by ultrasound by size and echogenicity. Both size and echogenicity are predictors of cardiovascular events. The aim of this study was to examine whether traditional risk factors and markers of inflammation and oxidation were associated with plaque size and echogenicity. Computerised analysis of carotid plaque size and echogenicity (grey scale median, GSM) were performed by ultrasound in a population-based health survey in 1,016 subjects aged 70 years (PIVUS study). Information on cardiovascular risk factors was collected, together with markers of inflammation and oxidation. Increased Framingham risk score, systolic blood pressure, higher BMI and decreased HDL, lower glutathione levels were related to echolucent plaques. Previous or present smoking was common with significantly more pack-years related to the echorich plaques. Plaque size was associated with increased Framingham risk score, systolic blood pressure, blood glucose levels, smoking, ApoB/A1 ratio, OxLDL, TNF alpha, HOMA insulin resistance, leucocyte count, decreased BCD-LDL and low levels of l-selectin. Low HDL, increased BMI and decreased glutathione levels were associated with the echolucency of carotid plaques, implying metabolic factors to play a role for plaque composition. Markers of inflammation were related to plaque size alone, implying inflammation to be predominantly associated with the amount of atherosclerosis. These results suggest that plaque size and echogenicity are influenced by different risk factors.
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| 2. |
- Ebeling Barbier, Charlotte, et al.
(författare)
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Clinically unrecognized myocardial infarction detected at MR imaging may not be associated with atherosclerosis
- 2007
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Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 0033-8419 .- 1527-1315. ; 245:1, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To prospectively investigate whether there is support for the hypothesis that clinically unrecognized myocardial infarctions (UMIs) detected at magnetic resonance (MR) imaging have an atherosclerotic pathogenesis similar to that of recognized myocardial infarctions (RMIs). Materials and Methods: After ethics committee approval and informed consent were obtained, gadolinium-enhanced whole-body MR angiography and late-enhancement MR imaging were performed in 248 randomly chosen 70-year-old subjects (123 women, 125 men). Imaging included the aorta and the carotid, renal, and lower limb arteries to the ankle, but not the coronary arteries. Subjects with myocardial infarction (MI) scars at late-enhancement MR imaging were classified as having RMI (n = 11) (those with a diagnosis of MI at the hospital) or UMI (n = 49) (those without a diagnosis of MI at the hospital). The presence of 50% or higher luminal narrowing in any vessel at whole-body MR angiography was considered to represent significant atherosclerosis. Intima-media thickness of the common carotid artery was measured with ultrasonography. C-reactive protein level was measured, and coronary heart disease risk was estimated. Observers were blinded to any previous results. The chi(2) test analysis of variance, and Bonferroni correction were used for statistical analyses. Results: None of the measured parameters differed significantly between the group without MI scars and the UMI group, but parameters were significantly increased in the RMI group (P < .05) compared with those in the group without MI scars. Forty-two of 49 UMIs and nine of 11 RMIs were located within inferolateral segments of the left ventricle. Conclusion: MR imaging-detected UMIs might have a different pathogenesis from that of RMIs or may have the same pathogenesis but may manifest at an earlier stage.
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| 3. |
- Eriksson, Daniel, et al.
(författare)
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Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison’s disease in Sweden
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.
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| 4. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 5. |
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| 6. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 7. |
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| 8. |
- Lind, Lars, et al.
(författare)
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Atherosclerosis measured by whole body magnetic resonance angiography and carotid artery ultrasound is related to arterial compliance, but not to endothelium-dependent vasodilation : the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study
- 2009
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 29:5, s. 321-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Arterial compliance and endothelium-dependent vasodilation are two characteristics of the vessel wall. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, we studied the relationships between arterial compliance and endothelium-dependent vasodilation versus atherosclerosis as measured with two imaging modalities. METHODS: In the population-based PIVUS study (1016 subjects aged 70), arterial compliance was determined by ultrasound in the carotid artery and the stroke volume to pulse pressure ratio by echocardiography, while endothelium-dependent vasodilation was assessed by the invasive forearm technique with acetylcholine and brachial artery ultrasound. Intima-media thickness was evaluated by ultrasound in the carotid artery (n = 954). Stenosis in the carotid, aorta, renal, upper and lower leg arteries were determined by magnetic resonance angiography in a random subsample of 306 subjects. RESULTS: After adjustments for gender, Framingham risk score, obesity, myocardial infarction and stroke, distensibility in the carotid artery and the stroke volume to pulse pressure ratio were both significantly related to a weighted index of stenosis in the five arterial territories evaluated by magnetic resonance angiography (p<0.02 for both). Distensibility in the carotid artery (P = 0.021), but not the stroke volume to pulse pressure ratio (P = 0.08), was also significantly related to intima-media thickness. CONCLUSION: In the elderly population, atherosclerosis is mainly related to arterial compliance, but not to endothelium-dependent vasodilation in peripheral conduit or resistance vessels.
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| 9. |
- Lind, Lars, et al.
(författare)
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Brachial artery intima-media thickness and echogenicity in relation to lipids and markers of oxidative stress in elderly subjects : --the prospective investigation of the vasculature in Uppsala Seniors (PIVUS) Study.
- 2008
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Ingår i: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 43:2, s. 133-41
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to relate brachial artery intima-media thickness (IMT) and the grey scale median of the intima-media complex (IM-GSM) to traditional cardiovascular risk factors and markers of inflammation and oxidative stress. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, a population-based study of 1016 subjects aged 70, brachial artery IMT and IM-GSM, who were evaluated by ultrasound. Lipids, thirteen markers of inflammation and nine markers of oxidative stress were measured. The Framingham risk score was related to IMT (p < 0.0001), but not to the IM-GSM. In univariate analysis, HDL-cholesterol, serum triglycerides, fasting glucose, smoking, HOMA insulin resistance index and oxidized LDL levels were related to IMT. HDL and LDL-cholesterol, triglycerides, VCAM-1, e-selectin, leukocyte count, conjugated diens, baseline conjugated diens (BCD)-LDL, antibodies to oxLDL, the GSSG/GSH glutathione ratio and homocysteine were related to IM-GSM. In multiple regression models, HDL-cholesterol, fasting glucose and oxLDL levels were the independently related to IMT (p = 0.01-0.04), while serum triglycerides, BCD-LDL and the GSSG/GSH ratio were independently related to IM-GSM (p = 0.0001-0.004). In conclusion, in addition to traditional lipid variables, markers of oxidative stress were associated with both thickness and echogenicity of the brachial artery intima-media complex. Thus, both thickness and echogenicity of the brachial artery intima-media complex might be useful biomarkers in the future.
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| 10. |
- Lind, Lars, et al.
(författare)
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Shear stress in the common carotid artery is related to both intima-media thickness and echogenecity : the prospective investigation of the vasculature in Uppsala seniors study
- 2009
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Ingår i: Clinical hemorheology and microcirculation. - 1386-0291 .- 1875-8622. ; 43:4, s. 299-308
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Tidskriftsartikel (refereegranskat)abstract
- It has previously been shown that the degree of shear stress (SS) in the carotid artery is related to both plaque occurrence and intima-media thickness (IMT). Since the echogenecity also is an important feature of plaques, we investigated if a reduced shear stress also is related to the echolucency of plaque and the intima-media complex. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, a population-based study of 1016 subjects aged 70, left common carotid artery diameter, IMT, the grey scale median (GSM) of the intima-media complex (IM-GSM) and the blood flow velocity were measured by ultrasound. Occurrence of plaque was noted, and the echogenecity of the plaques was visually estimated by the Gray-Weale classification. Shear stress was inversely related to both IMT and IM-GSM (p=0.0084 and p=0.003, respectively), independently of gender and coronary risk, estimated by the Framingham risk score. Shear stress was lower in subjects with carotid plaque (44% of the sample) than in those without (p=0.0013), and was inversely related to the echogenecity in the subjects with plaque (p=0.0092), independently of gender and coronary risk. A low shear stress in the common carotid artery was associated with both a thick IMT and an echolucent intima-media complex. A similar picture was seen when overt plaques were evaluated, suggesting that shear stress is of importance for both the extent and composition of atherosclerosis.
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