| 41. |
- Hagström, Emil, et al.
(författare)
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Plasma parathyroid hormone and the risk of cardiovascular mortality in the community
- 2009
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Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 119:21, s. 2765-2771
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking. METHODS AND RESULTS: The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL . min(-1) . 1.73 m(-2) and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality. CONCLUSIONS: Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.
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| 42. |
- Hagström, Emil, et al.
(författare)
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Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease
- 2018
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 283:1, s. 83-92
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Assess the risk of ischaemic events associated with psychosocial stress in patients with stable coronary heart disease (CHD).METHODS: Psychosocial stress was assessed by a questionnaire in 14 577 patients (median age 65.0, IQR 59, 71; 81.6% males) with stable CHD on optimal secondary preventive therapy in the prospective randomized STABILITY clinical trial. Adjusted Cox regression models were used to assess associations between individual stressors, baseline cardiovascular risk factors and outcomes.RESULTS: After 3.7 years of follow-up, depressive symptoms, loss of interest and financial stress were associated with increased risk (hazard ratio, 95% confidence interval) of CV death (1.21, 1.09-1.34; 1.15, 1.05-1.27; and 1.19, 1.08-1.30, respectively) and the primary composite end-point of CV death, nonfatal MI or nonfatal stroke (1.21, 1.13-1.30; 1.19, 1.11-1.27; and 1.17, 1.10-1.24, respectively). Living alone was related to higher risk of CV death (1.68, 1.38-2.05) and the primary composite end-point (1.28, 1.11-1.48), whereas being married as compared with being widowed, was associated with lower risk of CV death (0.64, 0.49-0.82) and the primary composite end-point (0.81, 0.67-0.97).CONCLUSIONS: Psychosocial stress, such as depressive symptoms, loss of interest, living alone and financial stress, were associated with increased CV mortality in patients with stable CHD despite optimal medical secondary prevention treatment. Secondary prevention of CHD should therefore focus also on psychosocial issues both in clinical management and in future clinical trials.
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| 43. |
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| 44. |
- Harnek, Jan, et al.
(författare)
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The 2011 outcome from the Swedish Health Care Registry on Heart Disease (SWEDEHEART)
- 2013
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 47, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) collects data to support the improvement of care for heart disease. Design. SWEDEHEART collects on-line data from consecutive patients treated at any coronary care unit n = (74), followed for secondary prevention, undergoing any coronary angiography, percutaneous coronary intervention, percutaneous valve or cardiac surgery. The registry is governed by an independent steering committee, the software is developed by Uppsala Clinical Research Center and it is funded by The Swedish national health care provider independent of industry support. Approximately 80,000 patients per year enter the database which consists of more than 3 million patients. Results. Base-line, procedural, complications and discharge data consists of several hundred variables. The data quality is secured by monitoring. Outcomes are validated by linkage to other registries such as the National Cause of Death Register, the National Patient Registry, and the National Registry of Drug prescriptions. Thanks to the unique social security number provided to all citizens follow-up is complete. The 2011 outcomes with special emphasis on patients more than 80 years of age are presented. Conclusion. SWEDEHEART is a unique complete national registry for heart disease.
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| 45. |
- Harrington, Robert A., et al.
(författare)
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The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial : study design and rationale
- 2009
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 158:3, s. 327-334
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Tidskriftsartikel (refereegranskat)abstract
- Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.
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| 46. |
- Harskamp, Ralf E., et al.
(författare)
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Use of thienopyridine prior to presentation with non-ST-segment elevation acute coronary syndrome and association with safety and efficacy of vorapaxar : insights from the TRACER trial
- 2017
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Ingår i: European Heart Journal. - : SAGE PUBLICATIONS LTD. - 2048-8726 .- 2048-8734. ; 6:2, s. 155-163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vorapaxar is effective in the prevention of secondary atherothrombotic events, although the efficacy/safety balance appears less favorable in the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). We hypothesized that patients with NSTE ACS already receiving thienopyridine prior to the ACS event may show differential efficacy/safety effects with vorapaxar vs. placebo added to their standard care. Methods: We studied 12,944 patients from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial with respect to thienopyridine use before admission for the index NSTE ACS event. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, rehospitalization for ischemia, and urgent revascularization. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Safety endpoints were bleeding complications. Results: Only 1513 patients (11.7%) were receiving thienopyridine before admission for the index NSTE ACS event. In these patients, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate/severe bleeding occurred in 5.7% treated with vorapaxar and 5.3% treated with a placebo (hazards ratio (HR) 1.10, 95% confidence interval (CI) 0.70-1.71); in thienopyridine-naive patients, the rates were 5.7% and 4.1%, respectively (HR 1.32, 95% CI 1.11-1.57; P-int=0.45). GUSTO severe bleeding in the prior thienopyridine group occurred in 0.5% of patients treated with vorapaxar and 1.3% of patients treated with placebo (HR 0.34, 95% CI 0.09-1.30); in thienopyridine-naive patients, the rates were 2.0% and 1.0%, respectively (HR 1.89, 95% CI 1.36-2.62; P-int=0.01). No interaction was observed between vorapaxar efficacy and prior thienopyridine use on the primary (adjusted P-int=0.53) or key secondary endpoints (P-int=0.61). Conclusions: TRACER was largely conducted in thienopyridine-naive patients with unknown tolerance to multiple antiplatelet treatments. Patients receiving thienopyridine before the index event may have had an attenuated increase in bleeding when adding vorapaxar, whereas concomitantly adding vorapaxar and thienopyridine in naive patients may have uncovered a latent susceptibility to bleeding.
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| 47. |
- Heerspink, Hiddo J L, et al.
(författare)
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A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function.
- 2022
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Ingår i: Kidney international. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 101:1, s. 174-184
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Tidskriftsartikel (refereegranskat)abstract
- This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function.
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| 48. |
- Heerspink, Hiddo J L, et al.
(författare)
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Effects of dapagliflozin on mortality in patients with chronic kidney disease : a pre-specified analysis from the DAPA-CKD randomized controlled trial.
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:13, s. 1216-1227
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death.METHODS AND RESULTS: DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo.CONCLUSION: In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.
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| 49. |
- Held, Claes, 1956-, et al.
(författare)
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Body Mass Index and Association With Cardiovascular Outcomes in Patients With Stable Coronary Heart Disease - A STABILITY Substudy
- 2022
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980 .- 2047-9980. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The obesity paradox states that patients with higher body mass index (BMI) and cardiovascular disease may experience better prognosis. However, this is less clear in patients with coronary heart disease. METHODS AND RESULTS: The prospective STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial included 15 828 patients with stable coronary heart disease with 3 to 5 years' follow-up on optimal secondary preventive treatment. BMI was measured at baseline (n=15 785). Associations between BMI and cardiovascular outcomes were evaluated by Cox regression analyses with multivariable adjustments. Mean age was 64 +/- 9 years and 19% women. Most risk markers (diabetes, hypertension, inflammatory biomarkers, triglycerides) showed a graded association with higher BMI. The frequency of smoking, levels of high-density lipoprotein, growth differentiation factor 15, and NT-proBNP (N-terminal pro-Btype natriuretic peptide) were higher at lower BMI. Low BMI (<20 kg/m(2); n=244 [1.5%]) was associated with doubled risk of total death (hazard ratio [HR], 2.27; 95% CI, 1.60-3.22), cardiovascular death (HR, 2.26; 95% CI, 1.46-3.49), and heart failure (HR, 2.51; 95% CI, 1.35-4.68) compared with BMI of 25 to <30 kg/m(2) (n=6752 [42.8%]) as reference. Similarly, high BMI of >= 35 kg/m(2) (n=1768 [11.2%]) was associated with increased risk of the same outcomes. A BMI between 20 and <25 kg/m(2) was associated with increased risk of cardiovascular death (HR, 1.26; 95% CI, 1.03-1.54) and total death (HR, 1.21; 95% CI, 1.03-1.42). CONCLUSIONS: Patients with stable coronary heart disease showed a graded increase in cardiometabolic and inflammatory risk factors with increasing BMI category >25 kg/m(2). All-cause and cardiovascular mortality were lowest at BMI of 25 to 35 kg/m(2). Underweight with BMI of <20 kg/m(2) and very high BMI of >= 35 kg/m(2) were strong risk markers for poor prognosis.
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| 50. |
- Held, Claes, 1956-, et al.
(författare)
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Characterization of cardiovascular clinical events and impact of event adjudication on the treatment effect of darapladib versus placebo in patients with stable coronary heart disease : Insights from the STABILITY trial
- 2019
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 208, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease.METHODS: Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results.RESULTS: In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03]).CONCLUSIONS: The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication.
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