| 1. |
- Berntsson, John, et al.
(författare)
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Increased vascular endothelial growth factor D is associated with atrial fibrillation and ischaemic stroke
- 2019
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 105:7, s. 553-558
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vascular endothelial growth factor D (VEGF-D) has important functions in lymphangiogenesis and angiogenesis. High plasma levels of VEGF-D have been associated with incidence of heart failure. The association of VEGF-D with atrial fibrillation (AF) and stroke is unclear and we hypothesised that VEGF-D could also be associated with incidence of AF and ischaemic stroke. Methods: VEGF-D was measured in fasting blood samples of 4689 subjects (40% men) without a history of AF from the Malmö Diet and Cancer Study, a prospective, population-based study in Sweden. Median age was 58 years (range 46-68). Cox regression analyses, adjusted for multiple risk factors, was used to assess AF and ischaemic stroke risk in relation to VEGF-D levels. Results: During a median follow-up time of 20.6 years, there were 637 cases of incident AF and 322 cases of first ischaemic stroke. After adjustment, VEGF-D was significantly associated with AF (HR 1.13(95% CI 1.04 to 1.23) per 1 SD increase) and ischaemic stroke (HR 1.14(95% CI 1.02 to 1.28) per 1 SD). The association with ischaemic stroke was explained by an increased incidence of AF-related stroke. HRs per 1 SD were 1.34 (95% CI 1.04 to 1.71) for AF-related ischaemic stroke and 1.04 (95% CI 0.90 to 1.19) for ischaemic stroke without AF. Conclusions: Increased VEGF-D concentrations were associated with AF and ischaemic stroke. The relationship with ischaemic stroke was more pronounced in subjects with a diagnosis of AF.
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| 2. |
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| 3. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 4. |
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| 5. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 6. |
- Sveen, Kari Anne, et al.
(författare)
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High levels of autoantibodies against apoB100 p210 are associated with lower incidence of atrial fibrillation in women
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 291:2, s. 207-217
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives Atrial fibrillation (AF) is associated with inflammation systemically and in the atrial tissue. Oxidized low-density lipoprotein (LDL) is increased in patients with AF and is suggested to be one of the molecules that drives inflammation. Autoantibodies against oxidized LDL and apolipoprotein B100, the protein component of LDL, are linked to atherosclerotic disease. However, whether these autoantibodies are associated with occurrence of AF is not known. We investigated autoantibodies against oxidized apolipoprotein B100 peptides and incidence of AF in a large population-based cohort. Methods IgM and IgG against native and aldehyde-modified apoB100 peptides 210 (p210) and 45 were analyzed by enzyme-linked immunosorbent assay (ELISA) in 5169 individuals from the Malmo Diet and Cancer cohort. Results Seven hundred sixty-nine incident AF cases were recorded during a follow-up of 21.3 years. Individuals with high levels of IgM against native p210 at baseline had a lower risk to develop AF; however, the association did not remain after adjustment for age and sex. Women had higher levels of IgM against native p210 than men (0.70 +/- 0.22 AU vs. 0.63 +/- 0.21 AU, p < 0.001). The association of IgM against native p210 and AF was significantly different between sexes (p for interaction = 0.024), where females with high IgM against p210 had a lower risk for incidence of AF (hazard ratio [95% confidence interval] 4th versus 1st quartile: 0.67 [0.49-0.91]; p = 0.01) after adjusting for risk factors and comorbidities. Conclusion These findings support an association of humoral autoimmunity with AF.
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| 7. |
- Acosta, Stefan, et al.
(författare)
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B-type natriuretic peptide for prediction of incident clinically significant abdominal aortic aneurysm : A population-based prospective study
- 2018
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Ingår i: Vascular Medicine. - 1477-0377. ; 23:1, s. 46-51
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Tidskriftsartikel (refereegranskat)abstract
- Pathogenesis of abdominal aortic aneurysm (AAA) is unclear. The aim of this study was to evaluate inflammatory and hemodynamic plasma biomarkers as predictors for AAA in the prospective longitudinal cohort of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer Study ( n=5551; 1991-94). C-reactive protein, cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional pro-atrial natriuretic peptide (MR-proANP) and conventional risk factors at baseline were measured in patients with incident AAA during follow-up and compared to individuals without a diagnosis of AAA. Subjects were followed until 31 December 2013. Multivariable analyses were expressed in terms of hazard ratios (HR) per 1 standard deviation increment of each respective log-transformed plasma biomarker in the Cox proportional hazard models. Mean follow-up time was 20.7 years. Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%). Mean age of individuals with incident AAA was 59.7 years at study entry and AAA was diagnosed on average 14 years later. Adjusting for age, sex, smoking, body mass index, hypertension and diabetes mellitus, N-BNP (HR 1.29; 95% CI 1.03-1.62), but not MR-proANP (HR 1.20; 95% CI 0.95-1.50), was independently associated with incident AAA. In conclusion, the plasma biomarker N-BNP was associated with future development of AAA, which implies that this marker is a sensitive indicator of early subclinical cardiovascular disease.
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| 8. |
- Acosta, Stefan, et al.
(författare)
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Circulating Midregional Proadrenomedullin and Risk of Incident Abdominal Aortic Aneurysm : A Prospective Longitudinal Cohort Study
- 2018
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Ingår i: Angiology. - : SAGE Publications. - 0003-3197 .- 1940-1574. ; 69:4, s. 333-338
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Tidskriftsartikel (refereegranskat)abstract
- Prospective clinical plasma biomarker studies in abdominal aortic aneurysm (AAA) pathogenesis have been hampered by the need for very large cohorts and long follow-up time. The main aim of the present study was to evaluate the association of adrenomedullin, a cardiovascular (CV) stress marker, and incident AAA risk. Prospective longitudinal cohort of middle-aged individuals from the CV cohort of the Malmö Diet and Cancer Study (n = 5551; 1991-1994) was assessed. Plasma concentrations of midregional proadrenomedullin (MR-proADM), C-reactive protein (CRP), and conventional risk factors were measured at baseline. Incidence of AAA was studied up to December 31, 2013. Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%). Mean age of individuals with incident AAA was 59.7 years at study entry, and AAA was diagnosed on average 14 years later. Adjusting for age, gender, smoking, body mass index, hypertension, diabetes mellitus, and CRP, MR-proADM (hazard ratio: 1.28; 95% confidence interval: 1.01-1.62) was independently associated with incident AAA. The plasma biomarker MR-proADM seems to be a marker of AAA risk, implying that AAA development may be driven by long-standing CV stress on the aortic wall.
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| 9. |
- Acosta, Stefan, et al.
(författare)
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Lp-PLA2 activity and mass for prediction of incident abdominal aortic aneurysms : A prospective longitudinal cohort study
- 2017
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 262, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims The pathogenesis of abdominal aortic aneurysm (AAA) shares several common pathways with atherosclerosis. Prospective clinical plasma biomarker studies in AAA have been hampered by the need for very large cohorts and long follow-up time. Methods We analyzed a prospective longitudinal cohort of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (n = 5551; 1991-94). The plasma biomarkers lipoprotein-associated phospholipase A2 (Lp-PLA2 activity and mass), proneurotensin and C-reactive protein, and conventional risk factors at baseline were measured in patients with incident AAA during follow-up, and compared to individuals without a diagnosis of AAA. Subjects were followed until December 31st, 2013. Multivariable analyses were expressed in terms of hazard ratios (HR) per 1 standard deviation increment of each respective log-transformed plasma biomarker in the Cox proportional hazard models. Results Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%) during a median follow-up period of 20.7 years. Overall, 84 individuals had an incident AAA, of whom 22 (26.2%) were operated on and 16 (19.0%) had ruptured. Mean age of individuals with incident AAA was 59.7 years at study entry and AAA was diagnosed on average 14 years later. When adjusting for age, gender, smoking, body mass index, hypertension, and diabetes mellitus, Lp-PLA2 activity (HR 1.40; 95% CI 1.15–1.72) and Lp-PLA2 mass (HR 1.23; 95% CI 1.00–1.51) were independently associated with incident AAA. Conclusions The plasma biomarkers Lp-PLA2 activity and mass were markers of AAA risk and this implies that AAA is an athero-thrombotic related disease.
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| 10. |
- Adamsson Eryd, Samuel, et al.
(författare)
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Carotid intima-media thickness is associated with incidence of hospitalized atrial fibrillation.
- 2014
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 233:2, s. 673-678
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Tidskriftsartikel (refereegranskat)abstract
- Carotid intima-media thickness (IMT) is a measure of arterial thickening and a risk predictor for myocardial infarction and stroke. It is unclear whether IMT also predicts atrial fibrillation (AF). We explored the association between IMT and incidence of first AF hospitalization in a population-based cohort.
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