| 1. |
- Wuopio, Jonas, et al.
(författare)
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Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years : a CLARICOR trial sub-study.
- 2018
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 278, s. 97-102
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The lysosomal cysteine proteases cathepsin B and S have been implicated in the atherosclerotic process. The present paper investigates the association between serum levels of cathepsin B and S and cardiovascular events and mortality in patients with stable coronary heart disease.METHODS: The CLARICOR trial is a randomised, placebo-controlled trial investigating the effect of clarithromycin versus placebo in patients with stable coronary heart disease. The outcome was time to either a cardiovascular event or all-cause mortality. The placebo group was used as discovery sample and the clarithromycin group as replication sample: n = 1998, n = 1979; mean age (years) 65, 65; 31%, 30% women; follow-up for 10 years; number of composite outcomes n = 1204, n = 1220; respectively. We used a pre-defined multivariable Cox regression model adjusting for inflammation, established cardiovascular risk factors, kidney function, and use of cardiovascular drugs.RESULTS: Cathepsin B was associated with an increased risk of the composite outcome in both samples after multivariable adjustment (discovery: multivariable ratio (HR) per standard deviation increase 1.12, 95% confidence interval (CI) 1.05-1.19, p < 0.001, replication; HR 1.14, 95% CI 1.07-1.21, p < 0.001). There was no significant association between cathepsin S and the composite outcome in either the discovery or replication sample after multivariable adjustment (p>0.45). Secondary analyses suggest that cathepsin B was predominantly associated with mortality rather than specific cardiovascular events.CONCLUSIONS: Cathepsin B, but not serum cathepsin S, was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease. The clinical implications of our findings remain to be established.
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| 2. |
- Højskov, Ida E, et al.
(författare)
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Early physical training and psycho-educational intervention for patients undergoing coronary artery bypass grafting. The SheppHeart randomized 2 × 2 factorial clinical pilot trial.
- 2015
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Ingår i: European journal of cardiovascular nursing : journal of the Working Group on Cardiovascular Nursing of the European Society of Cardiology. - : Oxford University Press (OUP). - 1873-1953. ; 15:6, s. 425-37
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Tidskriftsartikel (refereegranskat)abstract
- Patients undergoing coronary artery bypass graft surgery often experience a range of problems and symptoms such as immobility, pain and insufficient sleep. Results from trials investigating testing in-hospital physical exercise or psychological intervention have been promising. However, no randomized clinical trials have tested a comprehensive rehabilitation programme consisting of both physical exercise and psycho-education in the early rehabilitation phase.
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| 3. |
- Nielsen, Niklas, et al.
(författare)
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Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial
- 2013
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management (TTM) strategy is not known. To prevent outcome reporting bias, selective reporting and data-driven results, we present the a priori defined detailed statistical analysis plan as an update to the previously published outline of the design and rationale for the TTM trial. Methods: The TTM trial is an investigator-initiated, multicenter, international, randomized, parallel-group, and assessor-blinded clinical trial of temperature management in 950 adult unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients are randomized to a TTM of either 33 degrees C or 36 degrees C after return of spontaneous circulation. The primary outcome is all-cause mortality at maximal follow-up (until end of the trial and a minimum of 180 days). The main secondary outcomes are the composite outcome of all-cause mortality and poor neurological function (Cerebral Performance Category (CPC) 3 and 4, and modified Rankin Scale (mRS) 4 and 5) at hospital discharge and at 180 days; and assessment of safety and harm: bleeding, infections, electrolyte and metabolic disorders, seizures, cardiac arrhythmia, and renal replacement therapy. Conclusion: The TTM trial investigates potential benefit and harm of two target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.
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| 4. |
- Nielsen, Niklas, et al.
(författare)
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Targeted Temperature Management at 33 degrees C versus 36 degrees C after Cardiac Arrest
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 369:23, s. 2197-2206
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundUnconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. MethodsIn an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33 degrees C or 36 degrees C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. ResultsIn total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33 degrees C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36 degrees C group (225 of 466 patients) (hazard ratio with a temperature of 33 degrees C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33 degrees C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36 degrees C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. ConclusionsIn unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.)
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| 5. |
- Carlsson, Axel C, et al.
(författare)
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10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease : A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980 .- 2047-9980. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.
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| 6. |
- Højskov, Ida Elisabeth, et al.
(författare)
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Early physical and psycho-educational rehabilitation in patients with coronary artery bypass grafting: A randomized controlled trial.
- 2019
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977. ; 51:2, s. 136-143
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Tidskriftsartikel (refereegranskat)abstract
- Rehabilitation of patients following coronary artery bypass grafting (CABG) has been widely studied; however, research into early rehabilitation after CABG is sparse. The aim of this trial was to assess the impact of early rehabilitation, compared with usual care in patients following CABG.Randomized controlled trial.A total of 326 patients treated with CABG.Patients treated with CABG were randomized 1:1 to 4 weeks of comprehensive early rehabilitation or usual care. The primary outcome was the Six Minute Walk Test (6MWT). Secondary outcomes were mental health and physical activity (Medical Outcome Study Short Form; SF-12); anxiety and depression (Hospital Anxiety and Depression Scale; HADS); physical and emotional scores; sleep (Pittsburgh Sleep Quality Index; PSQI); pain (Örebro Musculoskeletal Screening Questionnaire; ÖMSQ) and muscle endurance (Sit-To-Stand test).Sixteen patients dropped out. No significant differences between groups in the primary outcome (6MWT) were found after 4 weeks (p = 0.27). For secondary outcomes the odds ratio of HADS-D ≥ 8 decreased in favour of the experimental intervention (p = 0.04). There was non-adherence to parts of the intervention. Per-protocol analysis showed differences between groups for the 6MWT (p = 0.02) and the Sit-To-Stand test (p = 0.046).In general, the intervention had no effect on the 6MWT, or secondary outcomes, except for depressive symptoms. However, in adherent participants, the intervention had a positive effect for the primary and several secondary outcomes.
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| 7. |
- Højskov, Ida Elisabeth, et al.
(författare)
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SheppHeartCABG trial-comprehensive early rehabilitation after coronary artery bypass grafting: a protocol for a randomised clinical trial.
- 2017
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Patients undergoing coronary artery bypass graft surgery often experience a range of symptoms. Studies indicate that non-pharmacological interventions such as exercise training and psychoeducation have a positive physiological and psychological effect in early outpatient rehabilitation. The SheppHeartCABG trial will investigate the effect of early comprehensive rehabilitation in early phase rehabilitation versus usual care. The aim of this paper is to present the protocol for the SheppHeartCABG trial.SheppHeartCABG is an investigator-initiated randomised clinical superiority trial with blinded outcome assessment, employing 1:1 central randomisation to rehabilitation plus usual care versus usual care alone. On the basis of a sample size calculation, 326 patients undergoing coronary artery bypass grafting will be included from two clinical sites. All patients receive usual care and patients allocated to the experimental intervention follow 4 weeks rehabilitation consisting of an exercise programme, psycho-educative consultations and a compact mindfulness programme. The primary outcome is physical function measured by the 6-min walk test. The secondary outcomes are mental health and physical activity measured by the Medical Outcome Study Short Form (SF-12), anxiety and depression measured by the Hospital Anxiety and Depression Scale questionnaire, physical, emotional and global scores by the HeartQoL questionnaire, sleep measured by the Pittsburgh Sleep Quality Index, pain measured by the Örebro Musculoskeletal Screening Questionnaire and muscle endurance measured by the sit-to-stand test. A number of explorative analyses will also be conducted.SheppHeartCABG is approved by the regional ethics committee (no. H-4-2014-109) and the Danish Data Protection Agency (no. 30-1309) and is performed in accordance with good clinical practice and the Declaration of Helsinki in its latest form. Positive, neutral and negative results of the trial will be submitted to international peer-reviewed journals. Furthermore, results will be presented at national and international conferences relevant to the subject fields.NCT02290262; pre-results.
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| 8. |
- Nilsson, Erik, 1975-, et al.
(författare)
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Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up-A CLARICOR Trial Sub-Study
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Elevated pregnancy-associated plasma protein A (PAPP-A) is associated with mortality in acute coronary syndromes. Few studies have assessed PAPP-A in stable coronary artery disease (CAD) and results are conflicting. We assessed the 10-year prognostic relevance of PAPP-A levels in stable CAD. The CLARICOR trial was a randomized controlled clinical trial including outpatients with stable CAD, randomized to clarithromycin versus placebo. The placebo group constituted our discovery cohort (n = 1.996) and the clarithromycin group the replication cohort (n = 1.975). The composite primary outcome was first occurrence of cardiovascular event or death. In the discovery cohort, incidence rates (IR) for the composite outcome were higher in those with elevated PAPP-A (IR 12.72, 95% Confidence Interval (CI) 11.0-14.7 events/100 years) compared to lower PAPP-A (IR 8.78, 8.25-9.34), with comparable results in the replication cohort. Elevated PAPP-A was associated with increased risk of the composite outcome in both cohorts (discovery Hazard Ratio (HR) 1.45, 95% CI 1.24-1.70; replication HR 1.29, 95% CI 1.10-1.52). In models adjusted for established risk factors, these trends were attenuated. Elevated PAPP-A was associated with higher all-cause mortality in both cohorts. We conclude that elevated PAPP-A levels are associated with increased long-term mortality in stable CAD, but do not improve long-term prediction of death or cardiovascular events when added to established predictors.
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| 9. |
- Ruge, Toralph, et al.
(författare)
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Circulating endostatin as a risk factor for cardiovascular events in patients with stable coronary heart disease : A CLARICOR trial sub-study
- 2019
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 284, s. 202-208
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Raised levels of serum endostatin, a biologically active fragment of collagen XVIII, have been observed in patients with ischemic heart disease but association with incident cardiovascular events in patients with stable coronary heart disease is uncertain.METHODS: The CLARICOR-trial is a randomized, placebo-controlled trial of stable coronary heart disease patients evaluating 14-day treatment with clarithromycin. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease or all-cause mortality. In the present sub-study using 10-year follow-up data, we investigated associations between serum endostatin at entry (randomization) and the composite outcome and its components during follow-up. The placebo group was used as discovery sample (1204 events, n = 1998) and the clarithromycin-treated group as replication sample (1220 events, n = 1979).RESULTS: In Cox regression models adjusting for cardiovascular risk factors, glomerular filtration rate, and current pharmacological treatment, higher serum endostatin was associated with an increased risk of the composite outcome in the discovery sample (hazard ratio per standard deviation increase 1.11, 95% CI 1.03-1.19, p = 0.004), but slightly weaker and not statistically significant in the replication sample (hazard ratio 1.06, 95% CI 1.00-1.14, p = 0.06). In contrast, strong and consistent associations were found between endostatin and cardiovascular and all-cause mortality in all multivariable models and sub-samples. Addition of endostatin to a model with established cardiovascular risk factors provided no substantial improvement of risk prediction (<1%).CONCLUSIONS: Raised levels of serum endostatin might be associated with cardiovascular events in patients with stable coronary heart disease. The clinical utility of endostatin measurements remains to be established.
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| 10. |
- Winkel, Per, et al.
(författare)
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Prognostic value of routinely available data in patients with stable coronary heart disease. A 10-year follow-up of patients sampled at random times during their disease course
- 2018
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Ingår i: Open heart. - : BMJ. - 2053-3624. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective To characterise the long-term prognosis of patients with stable coronary artery heart disease by means of ‘standard predictors’ defined as demographic, clinical and biochemical quantities routinely available in general practices and ascertained at an interview not prompted by renewed cardiac complaints.Methods This is an observational study based on data from 2199 Copenhagen placebo patients from the ‘clarithromycin for patients with stable coronary heart disease’ trial of patients with stable coronary heart disease. In the trial, we compared the effects of 14 days of clarithromycin treatment versus placebo. The predictors were based on the interview forms and blood samples collected at entry, along with demographic information from hospital files.We studied ‘standard predictors’ of a composite outcome (myocardial infarction, unstable angina, cerebrovascular disease or all-cause death) and of all-cause death. Using Cox regression, we compared predictions of status at 3, 6 and 9 years without and with the use of ‘standard predictors’ and used receiver operating characteristic statistic.Results Few ‘standard predictors’ were associated (p<0.01) with the composite outcome or with all-cause death. When no ‘standard predictors’ were included, 63.2% of the model-based predictions of the composite outcome and 79.9% of death predictions were correct. Including all ‘standard predictors’ in the model increased the figures to 68.4% and 83.4%, respectively. C indices were low, except when all-cause death was assessed as a single outcome where C was 0.79.Conclusion ‘Standard predictors’ routinely available in general practices contribute only modestly to risk assessment in consecutively sampled patients with stable coronary heart disease as ascertained at a contact not prompted by renewed cardiac complaints. Novel biomarkers may improve the assessment.Trial registration number NCT00121550.
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