| 1. |
|
|
| 2. |
- Chen, Hao Yu, et al.
(författare)
-
Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis
- 2020
-
Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:6, s. 694-702
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.Objective: To identify novel genetic loci and pathways associated with AS.Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.Exposures: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.Results: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.
|
|
| 3. |
- Chen, H.Y., et al.
(författare)
-
Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
- 2023
-
Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
|
|
| 4. |
- Engström, Gunnar, et al.
(författare)
-
The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
|
|
| 5. |
- Hellström, Gustav, et al.
(författare)
-
Spawning migration behavior of salmon and sea trout in the Tornionjoki river system: Interim report 2018‒2019
- 2020
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Tornionjoki salmon and sea trout are closely monitored annually with multiple methods. Despite extensive data collection, some fundamental knowledge of the Tornionjoki salmon and sea trout relevant for modern adaptive salmon management is still lacking. Specifically, the in-river migratory behavior and survival of both pre- and post-spawning salmon and sea trout, as well as the distribution of spawning sites, are not well known. In addition, recent observations of sick and dying salmon in the Tornionjoki system, and declining returns reported from many rivers in connection with these observations, are concerning. More knowledge about how the disease symptoms affect behavior and survival of the Tornionjoki salmon is therefore needed. In-river migrations of Tonionjoki salmon and sea trout have been studied in cooperation between Luke and Swedish University of Agricultural Science (SLU) by means of radio telemetry in 2018‒2019. Radiotagging of salmon was carried out at the estuary from June to July (n = 227) and in the river in spring (May-June, n = 10) and autumn (August-October, n = 38). Sea trout were tagged in the river in spring (May-June, n = 33) and autumn (August-October, n = 59). Samples for age and genetic analysis were taken from all tagged individual, and the visual condition of the fish was classified in conjunction with the tagging. In both study years, a majority (61% in 2018; 83% in 2019) of the salmon tagged at the estuary returned to the sea by the end of July, i.e before spawning. Of the salmon that entered and stayed in the river until spawning, most of them were located below the Kattilakoski echo sounding place (c. 100 km from the sea) during spawning time. The salmon caught and tagged in the river showed a highly varying post-release behavior. In both study years, all salmon tagged in the spring moved downstream and descended to the sea or died during downstream movement. In contrast, all salmon tagged in autumn stayed in the river over the spawning time. Most of them stayed near the tagging site during the autumn, but some of them moved a long distance upstream after release. The tagged sea trout can be divided into two groups based on their migration pattern: (1) immature trout which moved into the lowermost river for overwintering and returned back to the sea in next spring, and (2) mature trout which ascended the river for spawning. The second group can be further divided into trout which entered the lowermost river in autumn and overwinter there before continuing to the spawning areas next spring, and trout which entered the river in springtime and continued to the spawning areas within the same season. In spawning time, autumn 2019, tagged trout were located in the main stem Tornionjoki and Muonionjoki, as well as in the tributaries Naamijoki, Äkäsjoki, Parkajoki and Merasjoki.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Neumann, Johannes Tobias, et al.
(författare)
-
Prognostic value of cardiovascular biomarkers in the population
- 2024
-
Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 331:22, s. 1898-1909
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years.Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein.Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses.Results: The analyses included 164054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people.Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality..
|
|
| 9. |
- Suneson, Klara, et al.
(författare)
-
Efficacy of eicosapentaenoic acid in inflammatory depression : study protocol for a match-mismatch trial
- 2022
-
Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Most antidepressant treatment studies have included patients strictly based on the Diagnostic and Statistical Manual of Mental Disorders definition of Major Depressive Disorder (MDD). Given the heterogeneity of MDD, this approach may have obscured inter-patient differences and hampered the development of novel and targeted treatment strategies. An alternative strategy is to use biomarkers to delineate endophenotypes of depression and test if these can be targeted via mechanism-based interventions. Several lines of evidence suggest that “inflammatory depression” is a clinically meaningful subtype of depression. Preliminary data indicate that omega-3 fatty acids, with their anti-inflammatory and neuroprotective properties, may be efficacious in this subtype of depression, and this study aims to test this hypothesis. Method: We conduct a match-mismatch-trial to test if add-on omega-3 fatty acid eicosapentaenoic acid (EPA) reduces depressive symptoms in patients with MDD and systemic low-grade inflammation. MDD patients on a stable antidepressant treatment are stratified at baseline on high sensitivity-C-reactive protein (hs-CRP) levels to a high-inflammation group (hs-CRP ≥ 3 mg/L) or a low-inflammation group (hs-CRP < 3 mg/L). Both groups receive add-on EPA (2 g per day) for 8 weeks with three study visits, all including blood draws. Patients and raters are blind to inflammation status. Primary outcome measure is change in Hamilton Depression Rating Scale score between baseline and week 8. We hypothesize that the inflammation group has a superior antidepressant response to EPA compared to the non-inflammation group. Secondary outcomes include a composite score of “inflammatory depressive symptoms”, quality of life, anxiety, anhedonia, sleep disturbances, fatigue, cognitive performance and change in biomarkers relating to inflammation, oxidative stress, metabolomics and cellular aging. Discussion: In this study we will, for the first time using a match-mismatch trial design, test if omega-3 is an efficacious treatment for inflammatory depression. If our study is successful, it could add to the field of precision psychiatry. Trial registration: This trial was registered May 8, 2017 on clinicaltrials.gov under the reference number NCT03143075.
|
|
| 10. |
- Suneson, Klara, et al.
(författare)
-
Inflammatory depression—mechanisms and non-pharmacological interventions
- 2021
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:4
-
Forskningsöversikt (refereegranskat)abstract
- Treatment of depression is hampered by the failure to identify distinct symptom profiles with distinct pathophysiologies that differentially respond to distinct treatments. We posit that inflammatory depression is a meaningful depression subtype associated with specific symptoms and biological abnormalities. We review several upstream, potentially causative, mechanisms driving low-grade inflammation in this subtype of depression. We also discuss downstream mechanisms mediating the link between inflammation and symptoms of depression, including alterations in dopaminergic neurotransmission and tryptophan metabolism. Finally, we review evidence for several non-pharmacological interventions for inflammatory depression, including probiotics, omega-3 fatty acids, and physical exercise interventions. While some evidence suggests that these interventions may be efficacious in inflammatory depression, future clinical trials should consider enriching patient populations for inflammatory markers, or stratify patients by inflammatory status, to confirm or refute this hypothesis.
|
|
