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Sökning: WFRF:(Greve Anders M.)

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1.
  • Hibar, Derrek P., et al. (författare)
  • Common genetic variants influence human subcortical brain structures
  • 2015
  • Ingår i: Nature. - 0028-0836. ; 520:7546, s. 224-U216
  • Tidskriftsartikel (refereegranskat)abstract
    • The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume(5) and intracranial volume(6). These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 X 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
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2.
  • Bjorkman, Anne D., et al. (författare)
  • Tundra Trait Team : : A database of plant traits spanning the tundra biome
  • 2018
  • Ingår i: Global Ecology and Biogeography. - Wiley-Blackwell. - 1466-822X. ; 27:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Motivation: The Tundra Trait Team (TTT) database includes field-based measurements of key traits related to plant form and function at multiple sites across the tundra biome. This dataset can be used to address theoretical questions about plant strategy and trade-offs, trait–environment relationships and environmental filtering, and trait variation across spatial scales, to validate satellite data, and to inform Earth system model parameters. Main types of variable contained: The database contains 91,970 measurements of 18 plant traits. The most frequently measured traits (> 1,000 observations each) include plant height, leaf area, specific leaf area, leaf fresh and dry mass, leaf dry matter content, leaf nitrogen, carbon and phosphorus content, leaf C:N and N:P, seed mass, and stem specific density. Spatial location and grain: Measurements were collected in tundra habitats in both the Northern and Southern Hemispheres, including Arctic sites in Alaska, Canada, Greenland, Fennoscandia and Siberia, alpine sites in the European Alps, Colorado Rockies, Caucasus, Ural Mountains, Pyrenees, Australian Alps, and Central Otago Mountains (New Zealand), and sub-Antarctic Marion Island. More than 99% of observations are georeferenced. Time period and grain: All data were collected between 1964 and 2018. A small number of sites have repeated trait measurements at two or more time periods. Major taxa and level of measurement: Trait measurements were made on 978 terrestrial vascular plant species growing in tundra habitats. Most observations are on individuals (86%), while the remainder represent plot or site means or maximums per species. Software format: csv file and GitHub repository with data cleaning scripts in R; contribution to TRY plant trait database (www.try-db.org) to be included in the next version release.
3.
  • Greve, Anders M., et al. (författare)
  • Resting heart rate and risk of adverse cardiovascular outcomes in asymptomatic aortic stenosis : The SEAS study
  • 2015
  • Ingår i: International Journal of Cardiology. - 0167-5273. ; 180, s. 122-128
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An elevated resting heart rate (RHR) may be an early sign of cardiac failure, but its prognostic value during watchful waiting in asymptomatic aortic stenosis (AS) is largely unknown. Methods: RHR was determined by annual ECGs in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study of asymptomatic mild-to-moderate AS patients. Primary endpoint in this substudy was major cardiovascular events (MCEs) and secondary outcomes its individual components. Multivariable Cox-models using serially-measured RHR were used to examine the prognostic impact of RHR per se. Results: 1563 patients were followed for a mean of 4.3 years (6751 patient-years of follow-up), 553 (35%) MCEs occurred, 10% (n = 151) died, including 75 cardiovascular deaths. In multivariable analysis, baseline RHR was independently associated with MCEs (HR 1.1 per 10 min(-1) faster, 95% CI: 1.0-1.3) and cardiovascular mortality (HR 1.3 per 10 min(-1) faster, 95% CI: 1.0-1.7, both p <= 0.03). Updating RHR with annual in-study reexaminations, time-varying RHR was highly associated with excess MCEs (HR 1.1 per 10 min(-1) faster, 95% CI: 1.1-1.3) and cardiovascular mortality (HR 1.4 per 10 min(-1) faster, 95% CI: 1.2-1.7, both p <= 0.006). The association of RHR with MCEs and cardiovascular mortality was not dependent on atrial fibrillation status (both p >= 0.06 for interaction). Conclusions: RHR is independently associated with MCEs and cardiovascular death in asymptomatic AS (Clinicaltrials.gov; unique identifier NCT00092677).
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4.
  • Bang, Casper N., et al. (författare)
  • Antihypertensive treatment with β-blockade in patients with asymptomatic aortic stenosis and association with cardiovascular events
  • 2017
  • Ingår i: Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease. - Wiley-Blackwell Publishing Inc.. - 2047-9980. ; 6:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with aortic stenosis (AS) often have concomitant hypertension. Antihypertensive treatment with a beta-blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS.Methods and results: We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity-matched Cox regression and competing risk analyses were used to assess risk ratios for all-cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow-up of 4.3 +/- 0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all-cause mortality (hazard ratio 0.5, 95% confidence interval 0.3-0.7, P<0.001), cardiovascular death (hazard ratio 0.4, 95% confidence interval 0.2-0.7, P<0.001), and sudden cardiac death (hazard ratio 0.2, 95% confidence interval 0.1-0.6, P=0.004). This was confirmed in competing risk analyses (all P<0.004). No interaction was detected with AS severity (all P>0.1).Conclusions: In post hoc analyses Bbl therapy did not increase the risk of all-cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS. A prospective study may be warranted to determine if Bbl therapy is in fact beneficial.
5.
  • Bang, Casper N, et al. (författare)
  • Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study)
  • 2015
  • Ingår i: American Journal of Cardiology. - Elsevier. - 0002-9149. ; 116:12, s. 1840-1844
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment.
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6.
  • Greve, Anders M., et al. (författare)
  • Contrasting Hemodynamic Mechanisms of Losartan- vs. Atenolol-Based Antihypertensive Treatment : A LIFE Study
  • 2012
  • Ingår i: American Journal of Hypertension. - 0895-7061. ; 25:9, s. 1017-1023
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Pharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP). METHODS Data from all patients with at least two echocardiographic examinations in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) echocardiographic substudy (n = 801); high-risk patients on losartan- vs. atenolol-based antihypertensive therapy. Echocardiography was performed annually for 4 years to measure stroke index (SI), heart rate, cardiac index (CI), conduit artery stiffness assessed as pulse pressure/stroke index (PP/SI) and total peripheral resistance index (TPRI). RESULTS Atenolol- and losartan-based therapy reduced BP similarly (cumulative difference in mean brachial blood pressure 0.3 mm Hg, P = 0.65). After 4 years the cumulative means of SI and heart rate were 1.8 ml/m(2) higher and 5.7 beats/min lower on atenolol-based treatment, respectively (both P < 0.001). This kept CI below baseline in atenolol-treated patients, whereas in the losartan group CI was unchanged from baseline throughout the study. TPRI was decreased more and remained lower in the losartan group (cumulative difference in mean TPRI 287 dynes/sec(-5)/cm/m(2), P < 0.001). These findings partly explained univariate differences in systolic- and diastolic function indices between the two treatments; fully adjusted losartan was only associated with a smaller left atrial diameter (cumulative mean difference 0.07 cm; 95% confidence intervals, -0.13 to -0.01, P = 0.03). CONCLUSIONS Contrasting hemodynamics impacted cardiac response to similar reductions in brachial BP on losartan- vs. atenolol-based therapy. The similar reduction of PP/SI suggests that the antihypertensive regimens used in the LIFE study had comparable effects on arterial stiffness (LIFE study; NCT00338260)
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7.
  • Greve, Anders M., et al. (författare)
  • Effect Modifications of Lipid-Lowering Therapy on Progression of Aortic Stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis [SEAS] Study)
  • 2018
  • Ingår i: American Journal of Cardiology. - Elsevier. - 0002-9149. ; 121:6, s. 739-745
  • Tidskriftsartikel (refereegranskat)abstract
    • Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (p >= 0.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all p In conclusion, in a non prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677). 
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8.
  • Greve, Anders M., et al. (författare)
  • Usefulness of the electrocardiogram in predicting cardiovascular mortality in asymptomatic adults with aortic stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis study)
  • 2014
  • Ingår i: American Journal of Cardiology. - Elsevier. - 0002-9149. ; 114:5, s. 751-756
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypertension and coronary heart disease are common in aortic stenosis (AS) and may impair prognosis for similar AS severity. Different changes in the electrocardiogram may be reflective of the separate impacts of AS, hypertension, and coronary heart disease, which could lead to enhanced risk stratification in AS. The aim of this study was therefore to examine if combining prognostically relevant electrocardiographic (ECG) findings improves prediction of cardiovascular mortality in asymptomatic AS. All patients with baseline electrocardiograms in the SEAS study were included. The primary end point was cardiovascular death. Backward elimination (p > 0.01) identified heart rate, Q waves, and Cornell voltage-duration product as independently associated with cardiovascular death. Multivariate logistic and Cox regression models were used to evaluate if these 3 ECG variables improved prediction of cardiovascular death. In 1,473 patients followed for a mean of 4.3 years (6,362 patient-years of follow-up), 70 cardiovascular deaths (5%) occurred. In multivariate analysis, heart rate (hazard ratio [FIR] 1.5 per 11.2 minute(-1) [1 SD], 95% confidence interval [CI] 1.2 to 1.8), sum of Q-wave amplitude (HR 1.3 per 2.0 nun [1 SD], 95% CI 1.1 to 1.6), and Cornell voltage-duration product (FIR 1.4 per 763 mm x ms [1 SD], 95% CI 1.2 to 1.7) remained independently associated with cardiovascular death. Combining the prognostic information contained in each of the 3 ECG variables improved integrated discrimination for prediction of cardiovascular death by 2.5%, net reclassification by 14.3%, and area under the curve by 0.06 (all p <= 0.04) beyond other important risk factors. ECG findings add incremental predictive information for cardiovascular mortality in asymptomatic patients with AS.
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9.
  • Bang, Casper N., et al. (författare)
  • Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis : The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study
  • 2012
  • Ingår i: American Heart Journal. - Elsevier. - 0002-8703. ; 163:4, s. 690-696
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS). Methods Asymptomatic patients with mild-to-moderate AS (n = 1,421) were randomized (1: 1) to double-blind simvastatin 40 mg and ezetimibe 10 mg combination or placebo and followed up for a mean of 4.3 years. The primary end point was the time to new-onset AF adjudicated by 12-lead electrocardiogram at a core laboratory reading center. Secondary outcomes were the correlates of new-onset AF with nonfatal nonhemorrhagic stroke and a combined end point of AS-related events. Results During the course of the study, new-onset AF was detected in 85 (6%) patients (14.2/1,000 person-years of follow-up). At baseline, patients who developed AF were, compared with those remaining in sinus rhythm, older and had a higher left ventricular mass index a smaller aortic valve area index. Treatment with simvastatin and ezetimibe was not associated with less new-onset AF (odds ratio 0.89 [95% CI 0.57-1.97], P = .717). In contrast, age (hazard ratio [HR] 1.07 [95% CI 1.05-1.10], P < .001) and left ventricular mass index (HR 1.01 [95% CI 1.01-1.02], P < .001) were independent predictors of new-onset AF. The occurrence of new-onset AF was independently associated with 2-fold higher risk of AS-related outcomes (HR 1.65 [95% CI 1.02-2.66], P = .04) and 4-fold higher risk of nonfatal nonhemorrhagic stroke (HR 4.04 [95% CI 1.18-13.82], P = .03). Conclusions Simvastatin and ezetimibe were not associated with less new-onset AF. Older age and greater left ventricular mass index were independent predictors of AF development. New-onset AF was associated with a worsening of prognosis. (Am Heart J 2012;163:690-6.)
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10.
  • Bang, Casper N., et al. (författare)
  • Renin-angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis
  • 2014
  • Ingår i: International Journal of Cardiology. - 0167-5273. ; 175:3, s. 492-498
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Renin-angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild to moderate AS. Methods: All patients (n = 1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included. Risks of sudden cardiac death (SCD), cardiovascular death and all-cause mortality according to RASI treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses. Results: 769 (41%) patients received RASI. During a median follow-up of 4.3 +/- 0.9 years, 678 patients were categorized as having severe AS, 545 underwent aortic valve replacement, 40 SCDs, 103 cardiovascular and 205 all-cause deaths occurred. RASI was not associated with SCD (HR: 1.19 [95% CI: 0.50-2.83], p = 0.694), cardiovascular (HR: 1.05 [95% CI: 0.62-1.77], p = 0.854) or all-cause mortality (HR: 0.81 [95% CI: 0.55-1.20], p = 0.281). This was confirmed in propensity matched analysis (all p > 0.05). In separate analyses, RASI was associated with larger reduction in systolic blood pressure (p = 0.001) and less progression of LV mass (p = 0.040). Conclusions: RASI was not associated with SCD, cardiovascular or all-cause mortality in asymptomatic AS patients. However, RASI was associated with a potentially beneficial decrease in blood pressure and reduced LV mass progression. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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