1. |
- Alehagen, Urban, et al.
(author)
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Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of greater than= 50%
- 2015
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In: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS and WILKINS. - 1941-3289 .- 1941-3297. ; 8:5, s. 862-870
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Journal article (peer-reviewed)abstract
- Background The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as 50%. Methods and Results Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction 50% (age 7711 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72-0.89; Pless than0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82-0.96; P=0.003). Conclusions In heart failure with ejection fraction 50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.
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2. |
- Alehagen, Urban, et al.
(author)
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Association Between Use of Statins and Outcomes in Heart Failure With Reduced Ejection Fraction Prospective Propensity Score Matched Cohort Study of 21 864 Patients in the Swedish Heart Failure Registry
- 2015
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In: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 8:2, s. 252-260
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Journal article (peer-reviewed)abstract
- Background-In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). Methods and Results-In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age +/- SD, 72+/-12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1: 1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76-0.86; Pless than0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80-0.89; Pless than0.001). No examined baseline variables interacted with statin use except for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70-0.82, Pless than0.001) with IHD and 0.95 (95% confidence interval, 0.85-1.07; P=0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. Conclusions-In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.
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3. |
- Bank, Ingrid E. M., et al.
(author)
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Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients With Heart Failure
- 2017
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In: JACC. Heart failure. - : ELSEVIER SCI LTD. - 2213-1779 .- 2213-1787. ; 5:1, s. 14-24
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Journal article (peer-reviewed)abstract
- OBJECTIVES The study sought to compare the prevalence, clinical correlates and prognostic impact of diabetes in Southeast Asian versus white patients with heart failure (HF) with preserved or reduced ejection fraction. BACKGROUND Diabetes mellitus is common in HF and is associated with impaired prognosis. Asia is home to the majority of the worlds diabetic population, yet data on the prevalence and clinical significance of diabetes in Asian patients with HF are sparse, and no studies have directly compared Asian and white patients. METHODS Two contemporary population-based HF cohorts were combined: from Singapore (n 1,002, median [25th to 75th percentile] age 62 [54 to 70] years, 76% men, 19.5% obesity) and Sweden (n =19,537, 77 [68 to 84] years, 60% men, 24.8% obesity). The modifying effect of ethnicity on the relationship between diabetes and clinical correlates or prognosis (HF hospitalization and all-cause mortality) was examined using interaction terms. RESULTS Diabetes was present in 569 (57%) Asian patients versus 4,680 (24%) white patients (p amp;lt; 0.001). Adjusting for clinical covariates, obesity was more strongly associated with diabetes in white patients (odds ratio [OR]: 3.45;. 95% confidence interval [CI]: 2.86 to 4.17) than in Asian patients (OR: 1.82; 95% CI: 1.13 to 2.96; P-interaction = 0.026). Diabetes was more strongly associated with increased HF hospitalization and all-cause mortality in Asian patients (hazard ratio: 1.50; 95% CI: 1.21 to 1.87) than in white patients (hazard ratio: 1.29; 95% CI: 1.22 to 1.36; P-interaction = 0.045). CONCLUSIONS Diabetes was 3-fold more common in Southeast Asian compared to white patients with HF, despite younger age and less obesity, and more strongly associated with poor outcomes in Asian patients than white patients. These results underscore the importance of ethnicity-tailored aggressive strategies to prevent diabetes and its complications. (C) 2017 by the American College of Cardiology Foundation.
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4. |
- Batra, Gorav, et al.
(author)
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Association between heart failure quality of care and mortality : a population-based cohort study using nationwide registries
- 2022
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In: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 24:11, s. 2066-2077
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Journal article (peer-reviewed)abstract
- AIMS: To evaluate the quality of heart failure (HF) care using the European Society of Cardiology (ESC) quality indicators (QIs) for HF and to assess whether better quality of care is associated with improved outcomes.METHODS AND RESULTS: We performed a nationwide cohort study using the Swedish HF registry, consisting of patients with any type of HF at their first outpatient visit or hospitalization. Independent participant data for quality of HF care was evaluated against the ESC QIs for HF, and association with mortality estimated using multivariable Cox regression. In total, 43 704 patients from 80 hospitals across Sweden enrolled between 2013-2019 were included, with median follow-up 23.6 months. Of the 16 QIs for HF, 13 could be measured and 5 were inversely associated with all-cause mortality during follow-up. Higher attainment (≥50% vs. <50% attainment) of the composite opportunity-based score (combination of QIs into a single score) for patients with reduced ejection fraction was associated with lower all-cause mortality (adjusted hazard ratio 0.81; 95% confidence interval 0.72-0.91). Attainment of the composite score was less in the outpatient than inpatient setting (adjusted odds ratio 0.85; 95% confidence interval 0.72-0.99). Quality of care varied across hospitals, with assessment of health-related quality of life being the indicator with the widest variation in attainment (interquartile range 61.7%).CONCLUSION: Quality of HF care may be measured using the ESC HF QIs. In Sweden, attainment of HF care evaluated using the QIs demonstrated between and within hospital variation, and many QIs were inversely associated with mortality.
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5. |
- Becher, Peter Moritz, et al.
(author)
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Eligibility for sotagliflozin in a real-world heart failure population based on the SOLOIST-WHF trial enrolment criteria: data from the Swedish heart failure registry
- 2023
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In: European Heart Journal - Cardiovascular Pharmacotherapy. - : OXFORD UNIV PRESS. - 2055-6837 .- 2055-6845. ; 9:4, s. 343-352
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Journal article (peer-reviewed)abstract
- Aims The SOLOIST-WHF trial demonstrated efficacy of sotagliflozin in patients with type 2 diabetes mellitus (T2DM) and recent worsening heart failure (HF) regardless of ejection fraction (EF). Selection criteria in trials may limit their generalizability. Therefore, we aimed to investigate eligibility for sotagliflozin based on the SOLOIST-WHF criteria in a real-world HF population. Methods and results SOLOIST-WHF criteria were applied to patients stabilized after HF hospitalization in the Swedish HF Registry according to (i) literal scenario (all inclusion/exclusion criteria) or (ii) pragmatic scenario (only criteria likely to influence treatment decisions). Of 5453 inpatients with T2DM and recent worsening HF, 51.4% had reduced EF (HFrEF), 19.1% mildly reduced (HFmrEF), and 29.5% preserved EF (HFpEF). Eligibility (literal) was: 27.2% (32.4% in HFrEF, 24.7% in HFmrEF, 19.7% in HFpEF) and eligibility (pragmatic) was 62.8% (69.1%, 60.3%, 53.4%, respectively). In the literal scenario, criteria limiting eligibility were HF duration <3 months, eGFR <30 ml/min/1.73 m(2), age >85 years, acute coronary syndrome <3 months, and insufficiently high N-terminal pro-B-type natriuretic peptide levels. Eligible vs. non-eligible patients had more severe HF, higher cardiovascular (CV) comorbidity burden, higher use of HF treatments, and higher event rates (all-cause death 30.8 vs. 27.2 per 100 patient-years, CV death 19.1 vs. 16.6, and HF hospitalization 36.7 vs. 24.0). Conclusion In this large, real-world HF cohort with T2DM, similar to 1/3 of patients were eligible for sotagliflozin in the literal and similar to 2/3 of patients in the pragmatic scenario. Eligible patients had more severe HF and higher event rates, in particular CV and HF events.
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6. |
- Becher, Peter Moritz, et al.
(author)
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Phenotyping heart failure patients for iron deficiency and use of intravenous iron therapy : data from the Swedish Heart Failure Registry
- 2021
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 23:11, s. 1844-1854
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Journal article (peer-reviewed)abstract
- Aims Iron deficiency (ID) is associated with poor prognosis regardless of anaemia. Intravenous iron improves quality of life and outcomes in patients with ID and heart failure (HF) with reduced ejection fraction (HFrEF). In the Swedish HF registry, we assessed (i) frequency and predictors of ID testing; (ii) prevalence and outcomes of ID with/without anaemia; (iii) use of ferric carboxymaltose (FCM) and its predictors in patients with ID. Methods and results We used multivariable logistic regressions to assess patient characteristics independently associated with ID testing/FCM use, and Cox regressions to assess risk of outcomes associated with ID. Of 21 496 patients with HF and any ejection fraction enrolled in 2017-2018, ID testing was performed in 27%. Of these, 49% had ID and more specifically 36% had ID-/anaemia-, 15% ID-/anaemia+, 29% ID+/anaemia-, and 20% ID+/anaemia+ (48%, 39%, 13%, 30% and 18% in HFrEF, respectively). Risk of recurrent all-cause hospitalizations was higher in patients with ID regardless of anaemia. Of 1959 patients with ID, 19% received FCM (24% in HFrEF). Important independent predictors of ID testing and FCM use were anaemia, higher New York Heart Association class, having HFrEF, and referral to HF specialty care. Conclusion In this nationwide HF registry, ID testing occurred in only about a quarter of the patients. Among tested patients, ID was present in one half, but only one in five patients received FCM indicating low adherence to current guidelines on screening and treatment.
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7. |
- Becher, Peter M., et al.
(author)
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Use of sodium-glucose co-transporter 2 inhibitors in patients with heart failure and type 2 diabetes mellitus : data from the Swedish Heart Failure Registry
- 2021
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 23:6, s. 1012-1022
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Journal article (peer-reviewed)abstract
- Aims Use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in real-world heart failure (HF) is poorly characterised. In contemporary patients with HF and type 2 diabetes mellitus (T2DM) we assessed over time SGLT2i use, clinical characteristics and outcomes associated with SGLT2i use. Methods and results Type 2 diabetes patients enrolled in the Swedish HF Registry between 2016-2018 were considered. We performed multivariable logistic regression models to assess the independent predictors of SGLT2i use and Cox regression models in a 1:3 propensity score-matched cohort and relevant subgroups to investigate the association between SGLT2i use and outcomes. Of 6805 eligible HF patients with T2DM, 376 (5.5%) received SGLT2i, whose use increased over time with 12% of patients on treatment at the end of 2018. Independent predictors of SGLT2i use were younger age, HF specialty care, ischaemic heart disease, preserved kidney function, and absence of anaemia. Over a median follow-up of 256 days, SGLT2i use was associated with a 30% lower risk of cardiovascular (CV) death/first HF hospitalisation (hazard ratio 0.70, 95% confidence interval 0.52-0.95), which was consistent regardless of ejection fraction, background metformin treatment and kidney function. SGLT2i use was also associated with a lower risk of all-cause and CV death, HF and CV hospitalisation, and CV death/myocardial infarction/stroke. Conclusion In a contemporary HF cohort with T2DM, SGLT2i use increased over time, was more common with specialist care, younger age, ischaemic heart disease, and preserved renal function, and was associated with lower mortality and morbidity.
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8. |
- Braunschweig, Frieder, et al.
(author)
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New York Heart Association functional class, QRS duration, and survival in heart failure with reduced ejection fraction : implications for cardiac resychronization therapy.
- 2017
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In: European Journal of Heart Failure. - : Wiley-Blackwell. - 1388-9842 .- 1879-0844. ; 19:3, s. 366-376
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Journal article (peer-reviewed)abstract
- AIMS: Symptom severity assessed by NYHA functional class and QRS duration are essential criteria for selection of heart failure (HF) patients for CRT. This study assessed the relationship between NYHA class, QRS duration, and survival in a nationwide HF registry.METHODS AND RESULTS: We studied 13 423 patients with HF in NYHA class II-IV and LVEF <40% in the Swedish Heart Failure Registry. Survival was followed via the Swedish Population Registry. Of 12 534 patients without CRT (age 71 ± 12 years, 29% women), 51% and 49% were in NYHA class II and III-IV, respectively. Patients in NYHA class II compared with class III-IV were younger (69 vs. 73 years), and had a better systolic function (49% vs. 58% with LVEF <30%), P <0.001 for all, and a favourable co-morbidity profile. QRS duration was 116 ± 29 ms in NYHA class II and 119 ± 29 ms in NYHA class III-IV with QRS ≥120 ms found in 37% vs. 44%, and an LBBB in 23% vs. 28% (P < 0.001 for all). Upon multivariable Cox regression adjusting for 40 clinically relevant variables, mortality risk was higher in NYHA class III-IV vs. class II, with a hazard ratio (HR) of 1.31, 95% confidence interval (CI) 1.23-1.40. Mortality was also higher with QRS prolongation ≥120 ms vs. narrow QRS. The HR in NYHA class II patients with non-LBBB was 1.19 (95% CI 1.05 - 1.36) and in those with LBBB it was 1.16 (95% CI 1.03-1.41). The corresponding HRs in NYHA class III-IV were 1.33 (95% CI 1.21-1.47) and 1.12 (95% CI 1.02-1.22). There was no significant interaction between the effects of NYHA class and QRS duration or morphology on mortality. Applying different scenarios to estimate guideline adherence, fewer patients with NYHA class II (range 14.4-42.6%) compared with NYHA class III-IV (18.0-45.4%) had received a CRT device when indicated.CONCLUSIONS: In HF with reduced LVEF, QRS prolongation is common and independently linked to worse survival. The increase in mortality risk associated with QRS prolongation of both LBBB and non-LBBB morphology is similar in NYHA class II and III-IV.
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9. |
- Cappelletto, Chiara, et al.
(author)
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Use of and association between heart failure pharmacological treatments and outcomes in obese versus non-obese patients with heart failure with reduced ejection fraction: data from the Swedish Heart Failure Registry
- 2023
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In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 25:5, s. 698-710
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Journal article (peer-reviewed)abstract
- Aims To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index >= 30 kg/m(2)) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. Conclusion Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk.
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10. |
- Cooper, Lauren B., et al.
(author)
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Association between potassium level and outcomes in heart failure with reduced ejection fraction: a cohort study from the Swedish Heart Failure Registry
- 2020
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In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:8, s. 1390-1398
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Journal article (peer-reviewed)abstract
- Aims Hyperkalaemia and hypokalaemia are common in heart failure and associated with worse outcomes. However, the optimal potassium range is unknown. We sought to determine the optimal range of potassium in patients with heart failure and reduced ejection fraction (amp;lt; 40%) by exploring the relationship between baseline potassium level and short- and long-term outcomes using the Swedish Heart Failure Registry from 1 January 2006 to 31 December 2012. Methods and results We assessed the association between baseline potassium level and all-cause mortality at 30 days, 12 months, and maximal follow-up, in uni- and multivariable stratified and restricted cubic spline Cox regressions. Of 13 015 patients, 93.3% had potassium 3.5-5.0 mmol/L, 3.7% had potassium amp;lt;3.5 mmol/L, and 3.0% had potassium amp;gt;5.0 mmol/L. Potassium 5.0 mmol/L were more common with lower estimated glomerular filtration rate and heart failure of longer duration and greater severity. The potassium level associated with the lowest hazard risk for mortality at 30 days, 12 months, and maximal follow-up was 4.2 mmol/L, and there was a steep increase in risk with both higher and lower potassium levels. In adjusted strata analyses, lower potassium was independently associated with all-cause mortality at 12 months and maximal follow-up, while higher potassium levels only increased risk at 30 days. Conclusion In this nationwide registry, the relationship between potassium and mortality was U-shaped, with an optimal potassium value of 4.2 mmol/L. After multivariable adjustment, hypokalaemia was associated with increased long-term mortality but hyperkalaemia was associated with increased short-term mortality.
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14. |
- Edner, Magnus, et al.
(author)
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Association between renin-angiotensin system antagonist use and mortality in heart failure with severe renal insufficiency: a prospective propensity score-matched cohort study
- 2015
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In: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 36:34, s. 2318-2326
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Journal article (peer-reviewed)abstract
- Aims In heart failure (HF) with reduced ejection fraction (EF), renin-angiotensin receptor (RAS) antagonists reduce mortality. However, severe renal insufficiency was an exclusion criterion in trials. We tested the hypothesis that RAS antagonists are associated with reduced mortality also in HF with severe renal insufficiency. Methods and results We studied patients with EF less than= 39% registered in the prospective Swedish Heart Failure Registry. In patients with creatinine greater than221 mu mol/L or creatinine clearance less than30 mL/min, propensity scores for RAS-antagonist use were derived from 36 variables. The association between RAS antagonist use and all-cause mortality was assessed with Cox regression in a cohort matched 1:1 based on age and propensity score. To assess consistency, we performed the same analysis as a positive control in patients without severe renal insufficiency. Between 2000 and 2013, there were 24 283 patients of which 2410 [age, mean (SD), 82 (9), 45% women] had creatinine greater than221 mu mol/L or creatinine clearance less than30 mL/min and were treated (n = 1602) or not treated (n = 808) with RAS antagonists. In the matched cohort of 602 vs. 602 patients [age 83 (8), 42% women], RAS antagonist use was associated with 55% [95% confidence interval (CI) 51-59] vs. 45% (41-49) 1-year survival, P less than 0.001, with a hazard ratio (HR) for mortality of 0.76 (95% CI 0.67-0.86, P less than 0.001). In positive control patients without severe renal insufficiency [n = 21 873; age 71 (12), 27% women], the matched HR was 0.79 (95% CI 0.72-0.86, P less than 0.001). Conclusion In HF with severe renal insufficiency, the use of RAS antagonists was associated with lower all-cause mortality. Prospective randomized trials are needed before these findings can be applied to clinical practice.
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15. |
- Eklind-Cervenka, Maria, et al.
(author)
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Association of Candesartan vs Losartan With All-Cause Mortality in Patients With Heart Failure
- 2011
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In: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. - : Ama American Medical Association. - 0098-7484 .- 1538-3598. ; 305:2, s. 175-182
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Journal article (peer-reviewed)abstract
- Context Angiotensin II receptor blockers (ARBs) reduce combined mortality and hospitalization in patients with heart failure (HF) with reduced left ventricular ejection fraction. Different agents have different affinity for the AT(1) receptor and may have different clinical effects, but have not been tested against each other in HF. Objective To assess the association of candesartan vs losartan with all-cause mortality in patients with HF. Design, Setting, and Patients An HF registry (the Swedish Heart Failure Registry) of 30 254 unique patients registered from 62 hospitals and 60 outpatient clinics between 2000 and 2009. A total of 5139 patients (mean [SD] age, 74 [11] years; 39% women) were treated with candesartan (n=2639) or losartan (n=2500). Survival as of December 14, 2009, by ARB agent was analyzed by Kaplan-Meier method and predictors of survival determined by univariate and multivariate proportional hazard regression models, with and without adjustment for propensity scores and interactions. Stratified analyses and quantification of residual confounding were also performed. Main Outcome Measures All-cause mortality at 1 and 5 years. Results One-year survival was 90% (95% confidence interval [CI], 89%-91%) for patients receiving candesartan and 83% (95% CI, 81%-84%) for patients receiving losartan, and 5-year survival was 61% (95% CI, 54%-68%) and 44% (95% CI, 41%-48%), respectively (log-rank Pandlt;.001). In multivariate analysis with adjustment for propensity scores, the hazard ratio for mortality for losartan compared with candesartan was 1.43 (95% CI, 1.23-1.65; Pandlt;.001). The results persisted in stratified analyses. Conclusion In this registry of patients with HF, the use of candesartan compared with losartan was associated with a lower mortality risk.
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16. |
- Faxen, Jonas, et al.
(author)
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Associations between rheumatoid arthritis, incident heart failure, and left ventricular ejection fraction
- 2023
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In: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 259, s. 42-51
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Journal article (peer-reviewed)abstract
- Background Rheumatoid arthritis (RA) is an independent risk factor for heart failure (HF). Yet, the association between RA and left ventricular ejection fraction (LVEF) in incident HF is not well studied, nor are outcomes of HF in RA by LVEF.Methods We identified incident HF patients between 2003 and 2018 through the Swedish Heart Failure Registry, enriched with data from national health registers. Using logistic regression, associations between a prior diagnosis of RA and LVEF among HF patients and vs age, sex, and geographical area matched general population controls without HF were assessed. Additionally, associations between HF with vs without a prior diagnosis of RA, by LVEF, and outcomes up to 5 years after HF diagnosis were investigated using Cox regression. LVEF was primarily dichotomized at 40% and secondarily categorized as <40%, 40% to 49%, and >50%. Covariates included demographics and cardiovascular comorbidities. Results Among 20,916 incident HF patients, 331 (1.6%) had RA vs 1,047/103,501 (1.0%) of HF-free controls. The odds ratio (OR) for RA was 1.4 (95% CI: 1.1-1.8) in LVEF<40% vs HF-free controls and 1.6 (95% CI: 1.3-2.0) in LVEF>40% vs HF-free controls. Among HF patients, RA was more common in HF with LVEF >40% (1.9%) vs LVEF<40% (1.3%), corresponding to OR 1.4 (95% CI: 1.1-1.7). No associations between RA and cardiovascular outcomes were observed across LVEF. An association between RA and all-cause mortality was observed only for patients with LVEF<40% (hazard ratio: 1.4; 95% CI: 1.1-1.8).Conclusions RA was independently associated with incident HF, particularly HF with LVEF>40%. RA did not associate with cardiovascular outcomes following HF diagnosis but was associated with increased risk of all-cause mortality in HF with LVEF<40%. (Am Heart J 2023;259:42-51.)
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17. |
- Ferrannini, Giulia, et al.
(author)
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N-terminal pro-B-type natriuretic peptide concentrations, testing and associations with worsening heart failure events
- 2023
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In: ESC Heart Failure. - : WILEY PERIODICALS, INC. - 2055-5822.
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Journal article (peer-reviewed)abstract
- Aims: In patients with heart failure (HF), we aimed to assess (i) the time trends in N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing; (ii) patient characteristics associated with NT-proBNP testing; (iii) distribution of NT-proBNP levels, focusing on the subgroups with (WHFE) vs. without (NWHFE) a worsening HF event, defined as an HF hospitalization; and (iv) changes of NT-proBNP levels over time.Methods and results: NT-proBNP testing and levels were investigated in HF patients enrolled in the Swedish Heart Failure Registry (SwedeHF) linked with the Stockholm CREAtinine Measurements project from January 2011 to December 2018. Index date was the first registration in SwedeHF. Patterns of change in NT-proBNP levels before (in the previous 6 +/- 3 months) and after (in the following 6 +/- 3 months) the index date were categorized as follows: (i) <3000 ng/L at both measurements = stable low; (ii) <3000 ng/L at the first measurement and >= 3000 ng/L at the second measurement = increased; (iii) >= 3000 ng/L at the first measurement and <3000 ng/L at the second measurement = decreased; and (iv) >= 3000 ng/L at both measurements = stable high. Univariable and multivariable logistic regression models, expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs), were performed to assess the associations between (i) clinical characteristics and NT-proBNP testing and (ii) changes in NT-proBNP from 6 months prior to the index date and the index date and a WHFE. Consistency analyses were performed in HF with reduced ejection fraction (HFrEF) alone. A total of 4424 HF patients were included (median age 74 years, women 34%, HFrEF 53%), 33% with a WHFE. NT-proBNP testing increased over time, up to 55% in 2018, and was almost two-fold as frequent, and time to testing was less than half, in patients with WHFE vs. NWHFE. Independent predictors of testing were WHFE, higher heart rate, diuretic use, and preserved ejection fraction. Median NT-proBNP was 3070 ng/L (Q1-Q3: 1220-7395), approximately three-fold higher in WHFE vs. NWHFE. Compared with stable low NT-proBNP levels, increased (OR 4.27, 95% CI 2.47-7.37) and stable high levels (OR 2.48, 95% CI 1.58-3.88) were independently associated with a higher risk of WHFE. Results were consistent in the HFrEF population.Conclusions: NT-proBNP testing increased over time but still was only performed in half of the patients. Testing was associated with a WHFE, with features of more severe HF and for differential diagnosis purposes. Increased and stable high levels were associated with a WHFE. Overall, our data highlight the potential benefits of carrying further implementation of NT-proBNP testing in clinical practice.
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18. |
- Ferrari, Amerigo, et al.
(author)
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Sex differences in the prognostic role of achieving target doses of heart failure medications: Data from the Swedish Heart Failure Registry
- 2024
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In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844.
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Research review (peer-reviewed)abstract
- Aims Guidelines recommend target doses (TD) of heart failure (HF) with reduced ejection fraction (HFrEF) medications regardless of sex. Differences in pharmacokinetics and pharmacodynamics may explain heterogeneity in treatment response, adverse reactions, and tolerability issues across sexes. The aim of this study was to explore sex-based differences in the association between TD achievement and mortality/morbidity in HFrEF. Methods and results Patients with HFrEF and HF duration >= 6 months registered in the Swedish HF Registry between May 2000 and December 2020 (follow-up until December 2021) were analysed. Treatments of interest were renin-angiotensin system inhibitors (RASI) or angiotensin receptor-neprilysin inhibitors (ARNI), and beta-blockers. Multivariable Cox regression models were performed to explore the risk of cardiovascular mortality or hospitalization for HF across dose categories in females versus males. A total of 17 912 patients were analysed (median age 77.0 years, interquartile range [IQR] 70.0-83.0), 29% were female. Over a median follow-up of 1.33 years (IQR 0.29-3.22), for RASI/ARNI there was no significant difference in outcome for females achieving 50-99% versus 100% of TD (hazard ratio 0.92, 95% confidence interval 0.83-1.03), whereas males showed a gradual lowering in risk together with the achievement of higher % of TD (p-interaction = 0.030). For beta-blockers the achievement of TD was associated with the lowest risk of outcome regardless of sex. Conclusions Our findings suggest that females and males might differently benefit from the same dose of RASI/ARNI, and do represent a general call for randomized controlled trials to consider sex-specific up-titration schemes when testing HFrEF treatments in need of up-titration.
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19. |
- Gatti, Paolo, et al.
(author)
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What determines who gets cardiac resynchronization therapy in Europe? A comparison between ESC-HF-LT registry, SwedeHF registry, and ESC-CRT Survey II
- 2023
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In: European Heart Journal - Quality of Care and Clinical Outcomes. - : OXFORD UNIV PRESS. - 2058-5225 .- 2058-1742. ; 9:8, s. 741-748
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Journal article (peer-reviewed)abstract
- Aims Cardiac resynchronization therapy (CRT) is effective in heart failure with reduced ejection fraction (HFrEF) and dyssynchrony but is underutilized. In a cohort study, we identified clinical, organizational, and level of care factors linked to CRT implantation. Methods and results We included HFrEF patients fulfilling study criteria in the ESC-HF-Long Term Registry (ESC-HF-LT, n = 1031), the Swedish Heart Failure Registry (SwedeHF) (n = 5008), and the ESC-CRT Survey II (n = 11 088). In ESC-HF-LT, 36% had a CRT indication of which 47% had CRT, 53% had indication but no CRT, and the remaining 54% had no indication and no CRT. In SwedeHF, these percentages were 30, 25, 75, and 70%. Median age of patients with CRT indication and CRT present vs. absent was 68 vs. 65 years with 24% vs. 22% women in ESC-HF-LT, 76 vs. 74 years with 26% vs. 26% women in SwedeHF, and 70 years with 24% women in CRT Survey II (all had CRT). For ESC-HF-LT, independent predictors of having CRT were guideline-directed medical therapy (GDMT), atrial fibrillation (AF), prior HF hospitalization, and NYHA class. For SwedeHF, they were GDMT, age, AF, previous myocardial infarction, lower NYHA class, enrolment at university hospital, and follow-up at HF centre/Hospital. In SwedeHF, above median income and higher education level were also independently associated with having CRT. In the ESC-CRT Survey II (n = 11 088), all patients received CRT but with differences in the clinical characteristics between countries. Conclusion CRT was used in a minority of eligible patients and more used in ESC-HF-LT than in SwedeHF.
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20. |
- Gijsberts, Crystel M., et al.
(author)
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Ethnic differences in the association of QRS duration with ejection fraction and outcome in heart failure
- 2016
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In: Heart. - : BMJ PUBLISHING GROUP. - 1355-6037 .- 1468-201X. ; 102:18, s. 1464-1471
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Journal article (peer-reviewed)abstract
- Background QRS duration (QRSd) criteria for device therapy in heart failure (HF) were derived from predominantly white populations and ethnic differences are poorly understood. Methods We compared the association of QRSd with ejection fraction (EF) and outcomes between 839 Singaporean Asian and 11221 Swedish white patients with HF having preserved EF (HFPEF)and HF having reduced EF (HFREF) were followed in prospective population-based HF studies. Results Compared with whites, Asian patients with HF were younger (62 vs 74years, pamp;lt;0.001), had smaller body size (height 163 vs 171cm, weight 70 vs 80kg, both pamp;lt;0.001) and had more severely impaired EF (EF was amp;lt;30% in 47% of Asians vs 28% of whites). Overall, unadjusted QRSd was shorter in Asians than whites (101 vs 104ms, pamp;lt;0.001). Lower EF was associated with longer QRSd (pamp;lt;0.001), with a steeper association among Asians than whites (p(interaction)amp;lt;0.001), independent of age, sex and clinical covariates (including body size). Excluding patients with left bundle branch block (LBBB) and adjusting for clinical covariates, QRSd was similar in Asians and whites with HFPEF, but longer in Asians compared with whites with HFREF (p=0.001). Longer QRSd was associated with increased risk of HF hospitalisation or death (absolute 2-year event rate for 120ms was 40% and for amp;gt;120ms it was 52%; HR for 10ms increase of QRSd was 1.04 (1.03 to 1.06), pamp;lt;0.001), with no interaction by ethnicity. Conclusion We found ethnic differences in the association between EF and QRSd among patients with HF. QRS prolongation was similarly associated with increased risk, but the implications for ethnicity-specific QRSd cut-offs in clinical decision-making require further study.
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21. |
- Girerd, Nicolas, et al.
(author)
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Hypotension in heart failure is less harmful if associated with high or increasing doses of heart failure medication: Insights from the Swedish Heart Failure Registry
- 2023
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In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844.
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Journal article (peer-reviewed)abstract
- Aims Heart failure (HF) medication may reduce blood pressure (BP). Low BP is associated with worse outcomes but how this association is modified by HF medication has not been studied. We evaluated the association between BP and outcomes according to HF medication dose in HF with reduced ejection fraction (HFrEF). Methods and results We studied HFrEF patients from the Swedish HF registry (2000-2018). Associations between systolic BP (SBP) and cardiovascular death (CVD) and/or HF hospitalization (HFH) were analysed according to doses of renin-angiotensin system (RAS) inhibitors, beta-blockers and mineralocorticoid receptor antagonists (MRA). Among 42 040 patients (median age 74.0), lower baseline SBP was associated with higher risk of CVD/HFH (adjusted hazard ratio [HR] per 10 mmHg higher SBP: 0.92, 95% confidence interval [CI] 0.92-0.93), which was less high risk under optimized RAS inhibitor and beta-blocker doses (10% decrease in event rates per 10 mmHg SBP increase in untreated patients vs. 7% decrease in patients at maximum dose, both adjusted p < 0.02). Among the 13 761 patients with repeated measurements, 9.9% reported a SBP decrease >10 mmHg when HF medication doses were increased, whereas 24.6% reported a SBP decrease >10 mmHg with stable/decreasing doses. Decreasing SBP was associated with higher risk of CVD/HFH in patients with stable (HR 1.10, 95% CI 1.04-1.17) or decreasing (HR 1.29, 95% CI 1.18-1.42) HF medication dose but not in patients with an increase in doses (HR 0.94, 95% CI 0.86-1.02). Conclusions The association of lower SBP with higher risk of CVD/HFH is attenuated in patients with optimized HF medication. These results suggest that low or declining SBP should not limit HF medication optimization.
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22. |
- Guidetti, Federica, et al.
(author)
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Safety of continuing mineralocorticoid receptor antagonist treatment in patients with heart failure with reduced ejection fraction and severe kidney disease : data from Swedish Heart Failure Registry
- 2023
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In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 25:12, s. 2164-2173
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Journal article (peer-reviewed)abstract
- Aims: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD. Methods and results: We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30–44, 45–59 or ≥60 ml/min/1.73 m2, respectively. An eGFR ≥60 ml/min/1.73 m2 and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98–1.10), all-cause death (HR 1.02, 95% CI 0.97–1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95–1.02) across the eGFR spectrum including also severe CKD. Conclusions: The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum.
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23. |
- Gustafsson, Mika, et al.
(author)
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A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases
- 2015
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In: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 7:313
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Journal article (peer-reviewed)abstract
- Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.
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24. |
- Hållstam, Andrea, et al.
(author)
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Assessment and treatment at a pain clinic : a one-year follow-up of patients with chronic pain
- 2017
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In: Scandinavian Journal of Pain. - Amsterdam : Elsevier. - 1877-8860 .- 1877-8879. ; 17:1, s. 233-242
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Journal article (peer-reviewed)abstract
- Background and aims: Pain is one of the most common reasons for patients to seek primary health care. Pain relief is likely to be achieved for patients suffering from acute pain, but for individuals with chronic pain it is more likely that the condition will persist. These patients have the option of being referred to specialised pain clinics. However, the complexity surrounding chronic pain patients is not well studied in these settings. This study aimed to describe patients with chronic pain referred to a pain clinic by using the information submitted during their first visit and one year later and also to identify associations between baseline characteristics and improvements in health-related quality of life in the follow-up.Methods: This was a longitudinal observational study of a sample consisting of 318 patients referred to a pain clinic. One group of patients containing 271 individuals (median age 48, 64% females) was assessed and received conventional pain treatment (CPT group) and a second group of 47 patients (median age 53, 64% females) was assessed by a pain specialist and referred back to their physician with a treatment recommendation (assessment only, AO group). Patient-reported outcome measures in health-related quality of life (EQ-5D), pain intensity (VAS), mental health (HADS), insomnia (ISI), pain-related disability (PDI), kinesiophobia (TSK) and sense of coherence (SOC) were collected at the first visit and one year later.Results: At baseline, the CPT group reported a low EQ-5D Index (median (md) 0.157) and EQVAS (md 40) as well as considerable high, current pain intensity VAS (md 58), HADS anxiety (md 8), ISI (md 17), PDI (md 36) and TSK (md 39). The AO group showed similar problems (no significant differences compared to the CPT group), except for ISI, where the AO group reported less severe problems. At the one-year follow-up, the CPT group had a statistically significant improvement in EQ-5D, VAS, ISI, PDI and TSK. In the AO group no significant changes were observed. In the CPT group there was an association between a high ISI level at baseline and an improved EQ-5D Index in the follow-up.Conclusions: The study describes rarely explored groups of patients with chronic pain at a pain clinic. Severe pain problems were present in both groups at their first visit. A statistically significant improvement could be seen in the group that was conventionally treated while this was not the case among those subjects who were assessed and referred. The results imply, that relatively limited treatment strategies were helpful for the patients' health-related quality of life. Despite these improvements, the patients were not fully recovered, pointing to the chronicity of pain conditions and the need of support for many patients.Implications: Increased knowledge about assessment, selection and treatment at pain clinics is important to improve the quality of the work performed at these clinics. Despite limited resources, further efforts should be made to collect comparable, valid data on a regular base from pain clinics in order to develop recommendation models.
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25. |
- Jackson, Alice M., et al.
(author)
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Apparent Treatment-Resistant Hypertension Across the Spectrum of Heart Failure Phenotypes in the Swedish HF Registry
- 2022
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In: JACC. Heart failure. - : ELSEVIER SCI LTD. - 2213-1779 .- 2213-1787. ; 10:6, s. 380-392
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Journal article (peer-reviewed)abstract
- BACKGROUND Hypertension is common in patients with heart failure (HF), but less is known about resistant hypertension.OBJECTIVES This study sought to investigate apparent treatment-resistant hypertension (aTRH) in patients with HF in the SwedeHF (Swedish Heart Failure Registry), across the spectrum of HF phenotypes (heart failure with reduced ejection fraction [HFrEF], heart failure with mildly reduced ejection fraction [HFmrEF], and heart failure with preserved ejection fraction [HFpEF]).METHODS aTRH was defined as systolic blood pressure $140 mm Hg ($135 mm Hg in diabetes) despite treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or sacubitril-valsartan, as well as a calcium-channel blocker and a diuretic; non-treatment-resistant hypertension (TRH) was defined as systolic blood pressure above these thresholds but not on the 3-drug combination; and normal blood pressure was defined as under these thresholds. In each left ventricular ejection fraction (LVEF) category, patient factors associated with aTRH and non-TRH and out-comes (HF hospitalization and cardiovascular death composite, its components, and all-cause death) according to hy-pertension category were examined.RESULTS Among 46,597 patients, aTRH was present in 2,693 (10%), 1,514 (14%), and 1,450 (17%) patients with HFrEF, HFmrEF, and HFpEF, respectively. Older age, obesity, diabetes, and kidney disease were associated with a greater like-lihood of aTRH and non-TRH (vs normal blood pressure). Associations were generally similar irrespective of LVEF category. Compared with normal blood pressure, aTRH was associated with a lower adjusted risk of the composite outcome in HFrEF and HFmrEF (HR: 0.79 [95% CI: 0.74-0.85] and HR: 0.86 [95% CI: 0.77-0.96]) but not in HFpEF (HR: 0.93 [95% CI: 0.84-1.04]).CONCLUSIONS aTRH was most common in HFpEF and least common in HFrEF. Associated patient characteristics were similar irrespective of LVEF category. aTRH (vs normal blood pressure) was associated with a lower risk of first HF hospitalization or cardiovascular death in HFrEF and HFmrEF but not in HFpEF. (J Am Coll Cardiol HF 2022;10:380-392) (c) 2022 by the American College of Cardiology Foundation.
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