| 1. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 2. |
- Cleland, J. G. F., et al.
(författare)
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Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:1, s. 26-35
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Tidskriftsartikel (refereegranskat)abstract
- Aims Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF >= 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 >= 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF >= 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF >= 50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conculations Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.
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| 3. |
- Gero, D., et al.
(författare)
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Defining Global Benchmarks in Bariatric Surgery A Retrospective Multicenter Analysis of Minimally Invasive Roux-en-Y Gastric Bypass and Sleeve Gastrectomy
- 2019
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Ingår i: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 270:5, s. 859-867
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To define "best possible'' outcomes for bariatric surgery (BS)(Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]). Background: Reference values for optimal surgical outcomes in welldefined low-risk bariatric patients have not been established so far. Consequently, outcome comparison across centers and over time is impeded by heterogeneity in case-mix. Methods: Out of 39,424 elective BS performed in 19 high-volume academic centers from 3 continents between June 2012 and May 2017, we identified 4120 RYGB and 1457 SG low-risk cases defined by absence of previous abdominal surgery, concomitant procedures, diabetes mellitus, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, anticoagulation, BMI>50 kg/m(2) and age>65 years. We chose clinically relevant endpoints covering the intra- and postoperative course. Complications were graded by severity using the comprehensive complication index. Benchmark values were defined as the 75th percentile of the participating centers' median values for respective quality indicators. Results: Patients were mainly females (78%), aged 38+/-11 years, with a baseline BMI 40.8 +/- 5.8 kg/m(2). Over 90 days, 7.2% of RYGB and 6.2% of SG patients presented at least 1 complication and no patients died (mortality in nonbenchmark cases: 0.06%). The most frequent reasons for readmission after 90-days following both procedures were symptomatic cholelithiasis and abdominal pain of unknown origin. Benchmark values for both RYGB and SG at 90-days postoperatively were 5.5% Clavien-Dindo grade >= IIIa complication rate, 5.5% readmission rate, and comprehensive complication index <= 33.73 in the subgroup of patients presenting at least 1 grade >= II complication. Conclusion: Benchmark cutoffs targeting perioperative outcomes in BS offer a new tool in surgical quality-metrics and may be implemented in qualityimprovement cycle. ClinicalTrials.gov Identifier NCT03440138
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| 4. |
- Kotecha, D., et al.
(författare)
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Effect of age and sex on efficacy and tolerability of beta blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis
- 2016
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 353
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To determine the efficacy and tolerability of beta blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction < 0.45. The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model. Compared with placebo, beta blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by beta blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give beta blockers, 15.6% in those receiving placebo). Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive beta blockers to reduce the risk of death and admission to hospital.
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| 5. |
- Kotecha, D., et al.
(författare)
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Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 69:24, s. 2885-2896
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF). OBJECTIVES This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo. METHODS The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization. RESULTS A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval [CI]: 1.07 to 1.15; p < 0.0001) but not in AF (n = 3,034; HR: 1.03 per 10 beats/min; 95% CI: 0.97 to 1.08; p = 0.38). Beta-blockers reduced ventricular rate by 12 beats/min in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (HR: 0.73 vs. placebo; 95% CI: 0.67 to 0.79; p < 0.001), regardless of baseline heart rate (interaction p = 0.35). Beta-blockers had no effect on mortality in patients with AF (HR: 0.96, 95% CI: 0.81 to 1.12; p = 0.58) at any heart rate (interaction p = 0.48). A lower achieved resting heart rate, irrespective of treatment, was associated with better prognosis only for patients in sinus rhythm (HR: 1.16 per 10 beats/min increase, 95% CI: 1.11 to 1.22; p < 0.0001). CONCLUSIONS Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm. (C) 2017 by the American College of Cardiology Foundation.
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| 6. |
- Cannon, J. A., et al.
(författare)
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Clinical outcomes according to QRS duration and morphology in the Eplerenone in Mild Patients: Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF)
- 2015
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:7, s. 707-716
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Tidskriftsartikel (refereegranskat)abstract
- AimsWe examined the relationship between different degrees of QRS prolongation and different QRS morphologies and clinical outcomes in patients with heart failure, reduced ejection fraction (HF-REF), and mild symptoms in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF). We also evaluated the effect of eplerenone in these patients according to QRS duration/morphology. Methods and resultsPatients were categorized as: QRS duration (ms) (i) <120 (n = 1375); (ii) 120-149 (n = 517); and (iii) 150 (n = 383), and QRS morphology (i) normal (n = 1252); (ii) left bundle branch block (BBB) (n = 608); and (iii) right BBB/intraventricular conduction defect (IVCD) (n = 415). The outcomes examined were the composite of cardiovascular death or heart failure hospitalization and all-cause mortality. Both abnormal QRS duration and QRS morphology were associated with higher risk, e.g. the rates of the composite outcome were: 10.2, 17.6, and 15.5 per 100 patient-years in the <120, 120-149, and 150ms groups, respectively. Eplerenone reduced the risk of the primary outcome and mortality, compared with placebo, consistently across the QRS duration/morphology subgroups. ConclusionWe found that even moderate prolongation of QRS duration and right BBB/IVCD were associated with a high risk of adverse outcomes in HF-REF. Eplerenone was similarly effective, irrespective of QRS duration/morphology.
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| 7. |
- Haver, V. G., et al.
(författare)
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Telomere length and outcomes in ischaemic heart failure: data from the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA)
- 2015
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:3, s. 313-319
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Tidskriftsartikel (refereegranskat)abstract
- AimsLeucocyte telomere length is considered a marker of biological ageing and has been suggested to be shorter in patients with CAD and heart failure compared with healthy controls. The aim of this study was to determine whether telomere length is associated with clinical outcomes in patients with ischaemic heart failure and whether this association is superior to chronological age as defined by date of birth. Methods and resultsWe measured leucocyte telomere length in 3275 patients with chronic ischaemic systolic heart failure participating in the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA) study. The primary composite endpoint was cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, which occurred in 575 patients during follow-up. We observed a significant association of leucocyte telomere lengths with the primary endpoint (hazard ratio 1.10; 95% confidence interval 1.01-1.20; P=0.03). However, this observation was not superior to age as defined by date of birth. The neutral effect of rosuvastatin treatment on clinical outcomes was not modified by baseline telomere length. ConclusionBiological age as defined by leucocyte telomere length was associated with clinical outcomes in patients with ischaemic heart failure, but this association did not add prognostic information above age as defined by date of birth.
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| 8. |
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| 9. |
- van der Meer, P., et al.
(författare)
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Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure) Clinical and Prognostic Associations
- 2018
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Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear. METHODS AND RESULTS: We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0-12.0 g/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was -0.25 g/dL and + 1.00 g/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02-1.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04-1.63) than responders. CONCLUSIONS: A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers.
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| 10. |
- Chin, K. L., et al.
(författare)
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Aspirin does not reduce the clinical benefits of the mineralocorticoid receptor antagonist eplerenone in patients with systolic heart failure and mild symptoms: an analysis of the EMPHASIS-HF study
- 2016
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 18:9, s. 1175-1181
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: It is not known whether concomitant use of aspirin might attenuate the beneficial effects of mineralocorticoid receptor antagonists (MRAs). The purpose of this subgroup analysis was to explore the interaction between baseline aspirin treatment and the effect of eplerenone on the primary efficacy outcomes (composite of hospitalization for heart failure or cardiovascular mortality), its components, and safety markers [estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), and serum potassium >5.5 mmol/L] in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF). METHODS AND RESULTS: Patients with chronic heart failure, reduced ejection fraction (HFREF), and mild symptoms were enrolled in EMPHASIS-HF. We evaluated baseline characteristics according to aspirin use. We explored the interaction between aspirin and eplerenone, using Cox proportional hazards models providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) and P-values for interaction. Of the 2737 patients randomized, 1605 patients (58.6%) were taking aspirin. The beneficial effects of eplerenone on the primary endpoint were similar in patients not treated (adjusted HR 0.59, 95% CI 0.46-0.75) or treated (adjusted HR 0.71, 95% CI 0.59-0.87) with aspirin at baseline (interaction P-value = 0.19). We did not observe any significant modification of the safety markers by aspirin that was clinically meaningful. CONCLUSION: Aspirin use in patients with chronic systolic heart failure and mild symptoms did not substantially reduce the overall beneficial effects of the MRA eplerenone contrary to what has been described in some studies with ACE inhibitors.
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