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Sökning: WFRF:(Kober Lars)

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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: ; 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.
  • McMurray, John J V, et al. (författare)
  • Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.
  • 2019
  • Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 381, s. 1995-2008
  • Tidskriftsartikel (refereegranskat)abstract
    • In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death.Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups.Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.).
  • Solomon, Scott D, et al. (författare)
  • Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure.
  • 2020
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 141:5, s. 352-361
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: While disease modifying therapies exist for heart failure (HF) with reduced left ventricular ejection fraction (LVEF), few options are available for patients in the higher range of LVEF (>40%). Sacubitril/valsartan has been compared with a renin-angiotensin- system (RAS) inhibitor alone in two similarly designed clinical trials of patients with reduced and preserved LVEF, permitting examination of its effects across the full spectrum of LVEF. Methods: We combined data from PARADIGM-HF (LVEF eligibility≤40%; n=8,399) and PARAGON-HF (LVEF eligibility≥45%; n=4,796) in a prespecified pooled analysis. We divided randomized patients into LVEF categories:≤22.5% (n=1269), >22.5% to 32.5% (n=3987), >32.5% to 42.5% (n=3143), > 42.5% to 52.5% (n=1427), > 52.5% to 62.5% (n=2166), >62.5% (n=1202). We assessed time to first cardiovascular death and HF hospitalization, its components, and total heart failure hospitlizations, all-cause mortality and non-cardiovascular mortality. Incidence rates and treatment effects were examined across categories of LVEF. Results: Among 13,195 randomized patients, we observed lower rates of cardiovascular death and HF hospitalization, but similar rates of non-cardiovascular death, among patients in the highest vs. lowest groups. Overall sacubitril/valsartan was superior to RAS inhibition for first cardiovascular death or heart failure hospitalization (HR 0.84, 95% CI 0.78, 0.90), cardiovascular death (HR 0.84, 95% CI 0.76, 0.92), heart failure hospitalization (HR 0.84, 95% CI 0.77, 0.91), and all-cause mortality (HR 0.88, 95% CI 0.81, 0.96). The effect of sacubitril/valsartan was modified by LVEF (treatment-by-continuous LVEF interaction p=0.02), and benefit appeared to be present for individuals with EF primarily below the normal range, although the treatment benefit for cardiovascular death diminished at a lower ejection fraction. We observed effect modification by LVEF on the efficacy of sacubitril/valsartan in both men and women with respect to composite total HF hospitalizations and cardiovascular death, although women derived benefit to higher ejection fractions. Conclusions:The therapeutic effects of sacubitril/valsartan, compared with a RAS inhibitor alone, vary by LVEF, with treatment benefits, particularly for heart failure hospitalization, that appear to extend to patients with heart failure and mildly reduced ejection fraction. These therapeutic benefits appeared to extend to a higher LVEF range in women compared with men. Clinical Trial Registration: URL: https://clinicaltrials.gov PARAGON-HF Unique Identifier: NCT01920711. PARADIGM-HF Unique Identifier: NCT01035255.
  • Waziri, Homa, et al. (författare)
  • Short and long-term survival after primary percutaneous coronary intervention in young patients with ST-elevation myocardial infarction
  • 2016
  • Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 203, s. 697-701
  • Tidskriftsartikel (refereegranskat)abstract
    • The long-term prognosis of patients with ST-elevation myocardial infarction (STEMI) aged 45 years or younger and differences according to gender have not been well characterized. Methods: We included 16,685 consecutive STEMI patients from 2003 to 2012 (67,992 patient-years follow-up) from the Eastern Danish Heart Registry and the Swedish Coronary Angiography and Angioplasty Registry who were treated with primary percutaneous coronary intervention (PCI). Results: We identified 1026 (6.2%) patients up to 45 years of age (mean age: 40.7 vs. 66.3 years, P < 0.001). Patients in the young group were predominantly men (79.7% vs. 71.9%) and smokers (71.2% vs. 44.2%, P < 0.001) but with a lower prevalence of hypertension (17.3% vs. 39.3%), hyperlipidemia (18.0% vs. 23.8%), diabetes (9.0% vs. 12.4%) and previous myocardial infarction (6.9% vs. 12.2%, all P < 0.001) compared with older patients. Young patients had a 0.8% annualmortality. During the follow-up period 6.3% of young patients died vs. 28.5% of older patients (P < 0.001). Both 30-day-mortality (adjusted hazard ratio [HR] = 0.26, 95% confidence interval [CI]: 0.12-0.54, P < 0.001) and mortality after 30 days and onwards (HR = 0.25, CI: 0.17-0.37, P < 0.001) were significantly lower in the young group. There was no difference in short-term (HR = 0.78, CI: 0.32-1.90, P = 0.59) or long-term (HR = 0.62, CI: 0.33-1.91, P = 0.59) mortality between women and men in the young group (HR = 0.79, CI: 0.21-1.80, P = 0.39). Conclusions: STEMI patients, aged 45 years or younger, have an excellent prognosis after treatment with primary PCI. Long-termannual survival is more than 99% in these patients. Young women with STEMI do not have a worse long-term prognosis than young men with STEMI.
  • Andersson, Charlotte, et al. (författare)
  • A risk score for predicting 30-day mortality in heart failure patients undergoing non-cardiac surgery
  • 2014
  • Ingår i: European Journal of Heart Failure. - : Elsevier. - 1879-0844. ; 16:12, s. 1310-1316
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundHeart failure is an established risk factor for poor outcomes in patients undergoing non-cardiac surgery, yet risk stratification remains a clinical challenge. We developed an index for 30-day mortality risk prediction in this particular group. Methods and resultsAll individuals with heart failure undergoing non-cardiac surgery between October 23 2004 and October 31 2011 were included from Danish administrative registers (n=16827). In total, 1787 (10.6%) died within 30days. In a simple risk score based on the variables from the revised cardiac risk index, plus age, gender, acute surgery, and body mass index category the following variables predicted mortality (points): male gender (1), age 56-65years (2), age 66-75years (4), age 76-85years (5), or age >85years (7), being underweight (4), normal weight (3), or overweight (1), undergoing acute surgery (5), undergoing high-risk procedures (intra-thoracic, intra-abdominal, or suprainguinal aortic) (3), having renal disease (1), cerebrovascular disease (1), and use of insulin (1). The c-statistic was 0.79 and calibration was good. Mortality risk ranged from <2% for a score <5 to >50% for a score 20. Internal validation by bootstrapping (1000 re-samples) provided c-statistic of 0.79. A more complex risk score based on stepwise logistic regression including 24 variables at P<0.05 performed only slightly better, c-statistic=0.81, but was limited in use by its complexity. ConclusionsFor patients with heart failure, this simple index can accurately identify those at low risk for perioperative mortality.
  • Andersson, Charlotte, et al. (författare)
  • Noncardiac Surgery in Patients With Aortic Stenosis: A Contemporary Study on Outcomes in a Matched Sample From the Danish Health Care System
  • 2014
  • Ingår i: Clinical Cardiology. - : Wiley-Blackwell. - 1932-8737. ; 37:11, s. 680-686
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPast research has identified aortic stenosis (AS) as a major risk factor for adverse outcomes in noncardiac surgery; however, more contemporary studies have questioned the grave prognosis. To further our understanding of this, the risks of a 30-day major adverse cardiovascular event (MACE) and all-cause mortality were investigated in a contemporary Danish cohort. HypothesisAS is not an independent risk factor for adverse outcomes in noncardiac surgery. MethodsAll patients with and without diagnosed AS who underwent noncardiac surgery in 2005 to 2011 were identified through nationwide administrative registers. AS patients (n=2823; mean age, 75.5years, 53% female) were matched with patients without AS (n=2823) on propensity score for AS and surgery type. ResultsIn elective surgery, MACE (ie, nonfatal myocardial infarction, ischemic stroke, or cardiovascular death) occurred in 66/1772 (3.7%) of patients with AS and 52/1772 (2.9%) of controls (P=0.19), whereas mortality occurred in 67/1772 (3.8%) AS patients and 51/1772 (2.9%) controls (P=0.13). In emergency surgery, 163/1051 (15.5%) AS patients and 120/1051 (11.4%) controls had a MACE (P=0.006), whereas 225/1051 (21.4%) vs 179/1051 (17.0%) AS patients and controls died, respectively (P=0.01). Event rates were higher for those with symptoms (defined as use of nitrates, congestive heart failure, or use of loop diuretics), compared with those without symptoms (P<0.0001). ConclusionsAS is associated with high perioperative rates of MACE and mortality, but perhaps prognosis is, in practice, not much worse for patients with AS than for matched controls. Symptomatic patients and patients undergoing emergency surgery are at considerable risks of a MACE and mortality.
  • 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 .- 1097-6744. ; 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.)
  • Bang, Casper N., et al. (författare)
  • Four-Group Classification of Left Ventricular Hypertrophy Based on Ventricular Concentricity and Dilatation Identifies a Low-Risk Subset of Eccentric Hypertrophy in Hypertensive Patients
  • 2014
  • Ingår i: Circulation Cardiovascular Imaging. - 1941-9651 .- 1942-0080. ; 7:3, s. 422-429
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Left ventricular hypertrophy (LVH; high LV mass [LVM]) is traditionally classified as concentric or eccentric based on LV relative wall thickness. We evaluated the prediction of subsequent adverse events in a new 4-group LVH classification based on LV dilatation (high LV end-diastolic volume [EDV] index) and concentricity (mass/end-diastolic volume [M/EDV](2/3)) in hypertensive patients. Methods and Results-In the Losartan Intervention for Endpoint Reduction (LIFE) echocardiography substudy, 939 hypertensive patients with measurable LVM at baseline were randomized to a mean of 4.8 years of losartan- or atenolol-based treatment. Patients with LVH (LVM/body surface area >= 116 and >= 96 g/m(2) in men and woman, respectively) were divided into 4 groups-concentric nondilated (increased M/EDV, normal EDV), eccentric dilated (increased EDV, normal M/EDV), concentric dilated (increased M/EDV and EDV), and eccentric nondilated (normal M/EDV and EDV)-and compared with patients with normal LVM. Time-varying LVH classes were tested for association with all-cause and cardiovascular mortality and a composite end point of myocardial infarction, stroke, heart failure, and cardiovascular death in multivariable Cox analyses. At baseline, the LVs were categorized as eccentric nondilated in 12%, eccentric dilated in 20%, concentric nondilated in 29%, concentric dilated in 14%, and normal LVM in 25%. Treatment changed the prevalence of 4 LVH groups to 23%, 4%, 5%, and 7%; 62% had normal LVM after 4 years. In time-varying Cox analyses, compared with normal LVM, those with eccentric dilated and both concentric nondilated and dilated LVH had increased risks of all-cause or cardiovascular mortality or the composite end point, whereas the eccentric nondilated group did not. Conclusions-Hypertensive patients with relatively mild LVH without either increased LV volume or concentricity have similar risk of all-cause mortality or cardiovascular events because hypertensive patients with normal LVM seem to be a low-risk group.
  • Bang, Casper N. (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 .- 1874-1754. ; 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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