| 1. |
- Patel, Riyaz S., et al.
(author)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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In: Circulation. - 2574-8300. ; 12:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 2. |
- Patel, Riyaz S., et al.
(author)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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In: Circulation. - 2574-8300. ; 12:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 3. |
- Borg, Sabina, et al.
(author)
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Factors associated with non-attendance at exercise-based cardiac rehabilitation
- 2019
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In: BMC Sports Science, Medicine and Rehabilitation. - : BMC. - 2052-1847. ; 11
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Journal article (peer-reviewed)abstract
- BackgroundDespite its well-established positive effects, exercise-based cardiac rehabilitation (exCR) is underused in patients following an acute myocardial infarction (AMI). The aim of the study was to identify factors associated with non-attendance at exCR in patients post-AMI in a large Swedish cohort.MethodsA total of 31,297 patients who have suffered an AMI, mean age 62.4 ± 4 years, were included from the SWEDEHEART registry during the years 2010–2016. Comparisons between attenders and non-attenders at exCR were done at baseline for the following variables: age, sex, body mass index, occupational status, smoking, previous diseases, type of index cardiac event and intervention, and left ventricular function. Distance of residence from the hospital and type of hospital were added as structural variables in logistic regression analyses, with non-attendance at exCR at one-year follow-up as dependent, and with individual and structural variables as independent variables.ResultsIn total, 16,214 (52%) of the patients did not attend exCR. The strongest predictor for non-attendance was distance to the exCR centre (OR 1.75 [95% CI: 1.64–1.86]). Other predictors for non-attendance included smoking, history of stroke, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), AMI or diabetes, male sex, being retired vs. being employed, and being followed-up at a county hospital. Patients with ST-elevation myocardial infarction (STEMI) and those intervened with PCI or CABG were more likely to attend exCR.ConclusionsA distance greater than 16 km was associated with increased probability of non-attendance at exCR, as were smoking, a higher burden of comorbidities, and male sex. A better understanding of individual and structural factors can support the development of future rehabilitation services.
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| 4. |
- Buccheri, Sergio, et al.
(author)
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Assessing the Nationwide Impact of a Registry-Based Randomized Clinical Trial on Cardiovascular Practice The TASTE Trial in Perspective
- 2019
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In: Circulation. Cardiovascular Interventions. - : Lippincott Williams & Wilkins. - 1941-7640 .- 1941-7632. ; 12:3
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Journal article (peer-reviewed)abstract
- BACKGROUND: Registry-based randomized clinical trials have emerged as useful tools to provide evidence on the comparative efficacy and safety of different therapeutic strategies. However, it remains unknown whether the results of registry-based randomized clinical trials have a sizable impact on daily clinical practice. We sought, therefore, to describe the temporal trends in thrombus aspiration (TA) use in Sweden before, during, and after dissemination of the TASTE trial (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) results.METHODS AND RESULTS: From January 1, 2006, to December 31, 2017, we included all consecutive patients with ST-segment-elevation myocardial infarction undergoing percutaneous revascularization in Sweden. All patients were registered in the Swedish Coronary Angiography and Angioplasty Registry. A total of 55 809 ST-segment-elevation myocardial infarction patients were included. TA use in Sweden substantially decreased after dissemination of TASTE results (from 39.8% to 11.8% during and after TASTE, respectively). Substantial variability in TA use across treating centers was observed before TASTE (TA use ranging from 0% to 70%), but after TASTE both the interhospital variability and the frequency of TA use were markedly reduced. A constant shift in medical practice was seen about 4 months after dissemination of the TASTE trial results. Time trends for all-cause mortality and definite stent thrombosis at 30 days were not associated with variations in TA use (P values >0.05 using the Granger test).CONCLUSIONS: In Sweden, the results of the TASTE trial were impactful in daily clinical practice and led to a relevant decrease in TA use in ST-segment-elevation myocardial infarction patients undergoing percutaneous revascularization.
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| 5. |
- Buccheri, Sergio, et al.
(author)
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Bioabsorbable polymer everolimus-eluting stents in patients with acute myocardial infarction : A report from the Swedish Coronary Angiography and Angioplasty Registry
- 2018
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In: EuroIntervention. - 1774-024X .- 1969-6213. ; 14:5, s. 562-569
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Journal article (peer-reviewed)abstract
- Aims: The clinical performance of the SYNERGY drug-eluting stent (DES) in patients with acute myocardial infarction (MI) has not been investigated in detail. We sought to report on the outcomes after SYNERGY DES (Boston Scientific, Marlborough, MA, USA) implantation in patients with MI undergoing percutaneous revascularisation (PCI). Methods and results: We included all consecutive patients with MI undergoing PCI with the SYNERGY DES and newer-generation DES (n-DES group) in Sweden. From March 2013 to September 2016, a total of 36,292 patients, of whom 39.7% presented with ST-elevation MI, were included. As compared to patients in the n-DES group (n=31,403), patients in the SYNERGY group (n=4,889) were older and presented more often with left main or three-vessel disease involvement, as well as with restenotic lesions (p<0.001 for all parameters). The Kaplan-Meier estimates of ST at two years in the SYNERGY and n-DES groups were 0.69% and 0.81%, respectively (adjusted HR 1.00, 95% CI: 0.69-1.46; p=0.99). Clinically relevant restenosis was encountered in 1.48% and 1.25% of patients in the SYNERGY and n-DES groups, respectively (adjusted HR 1.05, 95% CI: 0.81-1.37; p=0.72). No differences in the risk of all-cause death and recurrent MI were found between the two groups after adjustment (adjusted HR 1.12, 95% CI: 0.98-1.28; p=0.10, and adjusted HR 0.95, 95% CI: 0.82-1.10; p=0.49, respectively). Conclusions: In a large and unselected cohort of patients with MI undergoing percutaneous revascularisation with the SYNERGY DES, stent performance and clinical outcomes did not differ compared with other n-DES up to two years.
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| 6. |
- Buccheri, Sergio, et al.
(author)
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Clinical and angiographic outcomes of bioabsorbable vs. permanent polymer drug-eluting stents in Sweden : a report from the Swedish Coronary and Angioplasty Registry (SCAAR)
- 2019
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 40:31, s. 2607-2615
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Journal article (peer-reviewed)abstract
- AIMS: Randomized clinical trials have consistently demonstrated the non-inferiority of bioabsorbable polymer drug-eluting stents (BP-DES) with respect to DES having permanent polymers (PP-DES). To date, the comparative performance of BP- and PP-DES in the real world has not been extensively investigated.METHODS AND RESULTS: From October 2011 to June 2016, we analysed the outcomes associated with newer generation DES use in Sweden. After stratification according to the type of DES received at the index procedure, a total of 16 504 and 79 106 stents were included in the BP- and PP-DES groups, respectively. The Kaplan-Meier estimates for restenosis at 2 years were 1.2% and 1.4% in BP- and PP-DES groups, respectively. Definite stent thrombosis (ST) was low in both groups (0.5% and 0.7% in BP- and PP-DES groups, respectively). The adjusted hazard ratio (HR) for either restenosis or definite ST did not differ between BP- and PP-DES [adjusted HR 0.95, 95% confidence interval (CI) 0.74-1.21; P = 0.670 and adjusted HR 0.79, 95% CI 0.57-1.09; P = 0.151, respectively]. Similarly, there were no differences in the adjusted risk of all-cause death and myocardial infarction (MI) between the two groups (adjusted HR for all-cause death 1.01, 95% CI 0.82-1.25; P = 0.918 and adjusted HR for MI 1.05, 95% CI 0.93-1.19; P = 0.404).CONCLUSION: In a large, nationwide, and unselected cohort of patients, percutaneous coronary intervention with BP-DES implantation was not associated with an incremental clinical benefit over PP-DES use at 2 years follow-up.
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| 7. |
- Fukaya, Eri, et al.
(author)
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Clinical and Genetic Determinants of Varicose Veins Prospective, Community-Based Study of approximate to 500 000 Individuals
- 2018
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In: Circulation. - 0009-7322 .- 1524-4539. ; 138:25, s. 2869-2880
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Journal article (peer-reviewed)abstract
- BACKGROUND: Varicose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease. METHODS: We applied machine learning to agnostically search for risk factors of varicose veins in 493 519 individuals in the UK Biobank. Predictors were further studied with univariable and multivariable Cox regression analyses (2441 incident events). A genome-wide association study of varicose veins was also performed among 337 536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development. RESULTS: Machine learning confirmed several known (age, sex, obesity, pregnancy, history of deep vein thrombosis) and identified several new risk factors for varicose vein disease, including height. After adjustment for traditional risk factors in Cox regression, greater height remained independently associated with varicose veins (hazard ratio for upper versus lower quartile, 1.74; 95% Cl, 1.51-2.01; P<0.0001). A genomewide association study identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/ limb biology. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins (inverse -variance weighted: odds ratio, 1.26; P=2.07x10(-16)). CONCLUSIONS: Using data from nearly a half -million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.
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| 8. |
- Hansen, Tomas, et al.
(author)
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Normal radiological lymph node appearance in the thorax
- 2019
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In: Diseases of the esophagus. - : OXFORD UNIV PRESS INC. - 1120-8694 .- 1442-2050. ; 32:10, s. 1-6
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Journal article (peer-reviewed)abstract
- Modern treatment of esophageal cancer is multimodal and highly dependent on a detailed diagnostic assessment of clinical stage, which includes nodal stage. Clinical appraisal of nodal stage is highly dependent on knowledge of normal radiological appearance, information of which is scarce. We aimed to describe lymph node appearance on computed tomography (CT) investigations in a randomly selected cohort of healthy subjects. In a sample of the Swedish Cardiopulmonary bioimage study, which investigates a sample of the Swedish population aged 50-64 years, the CT scans of 426 subjects were studied in detail concerning intrathoracic node stations relevant in clinical staging of esophageal cancer. With stratification for sex, the short axis of visible lymph nodes was measured and the distribution of lymph node sizes was calculated as well as proportion of patients with visible nodes above 5 and 10 millimeters for each station. Probability of having any lymph node station above 5 and 10 millimeters was calculated with a logistic regression model adjusted for age and sex. In the 214 men (aged: 57.3 +/- 4.1 years) and 212 women (aged: 57.8 +/- 4.4 years) included in this study, a total of 309 (72.5%) had a lymph node with a short axis of 5 mm or above was seen in at least one of the node stations investigated. When using 10 mm as a cutoff, nodes were visible in 29 (6.81%) of the subjects. Men had higher odds of having any lymph node with short axis 5 mm or above (OR 3.03 95% CI 1.89-4.85, P < 0.001) as well as 10 mm or above (OR 2.31 95% CI 1.02-5.23, P = 0.044) compared to women. Higher age was not associated with propensity for lymph nodes above 5 or 10 millimeters in this sample. We conclude that, in a randomly selected cohort of patients between 50 and 64 years, almost 10% of the men and 4% of the women had lymph nodes above 10 millimeters, most frequently in the subcarinal station (station 107). More than half of the patients had nodes above 5 millimeters on CT and men were much more prone to have this finding. The probability of finding lymph nodes in specific stations relevant of esophageal cancer is now described.
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| 9. |
- Jernberg, Tomas, et al.
(author)
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Impact of ischaemic heart disease severity and age on risk of cardiovascular outcome in diabetes patients in Sweden : A nationwide observational study
- 2019
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In: BMJ Open. - : BMJ. - 2044-6055. ; 9:4
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Journal article (peer-reviewed)abstract
- Objectives To compare short-term cardiovascular (CV) outcome in type 2 diabetes (T2D) patients without ischaemic heart disease (IHD), with IHD but no prior myocardial infarction (MI), and those with prior MI; and assess the impact on risk of age when initiating first-time glucose-lowering drug (GLD). Design Cohort study linking morbidity, mortality and medication data from Swedish national registries. Participants First-time users of GLD during 2007-2016. Outcomes Predicted cumulative incidence for the CV outcome (MI, stroke and CV mortality) was estimated. A Cox model was developed where age at GLD start and CV risk was modelled. Results 260 070 first-time GLD users were included, 221 226 (85%) had no IHD, 16 294 (6%) had stable IHD-prior MI and 22 550 (9%) had IHD+MI. T2D patients without IHD had a lower risk of CV outcome compared with the IHD populations (±prior MI), (3-year incidence 4.78% vs 5.85% and 8.04%). The difference in CV outcome was primarily driven by a relative greater MI risk among the IHD patients. For T2D patients without IHD, an almost linear association between age at start of GLD and relative risk was observed, whereas in IHD patients, the younger (<60 years) patients had a relative greater risk compared with older patients. Conclusions T2D patients without IHD had a lower risk of the CV outcome compared with the T2D populations with IHD, primarily driven by a greater risk of MI. For T2D patients without IHD, an almost linear association between age at start of GLD and relative risk was observed, whereas in IHD patients, the younger patients had a relative greater risk compared with older patients. Our findings suggest that intense risk prevention should be the key strategy in the management of T2D patients, especially for younger patients.
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| 10. |
- Katus, Hugo, et al.
(author)
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Early diagnosis of acute coronary syndrome
- 2017
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:41, s. 3049-3055
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Research review (peer-reviewed)abstract
- The diagnostic evaluation of acute chest pain has been augmented in recent years by advances in the sensitivity and precision of cardiac troponin assays, new biomarkers, improvements in imaging modalities, and release of new clinical decision algorithms. This progress has enabled physicians to diagnose or rule-out acute myocardial infarction earlier after the initial patient presentation, usually in emergency department settings, which may facilitate prompt initiation of evidence-based treatments, investigation of alternative diagnoses for chest pain, or discharge, and permit better utilization of healthcare resources. A non-trivial proportion of patients fall in an indeterminate category according to rule-out algorithms, and minimal evidence-based guidance exists for the optimal evaluation, monitoring, and treatment of these patients. The Cardiovascular Round Table of the ESC proposes approaches for the optimal application of early strategies in clinical practice to improve patient care following the review of recent advances in the early diagnosis of acute coronary syndrome. The following specific 'indeterminate' patient categories were considered: (i) patients with symptoms and high-sensitivity cardiac troponin <99th percentile; (ii) patients with symptoms and high-sensitivity troponin <99th percentile but above the limit of detection; (iii) patients with symptoms and high-sensitivity troponin >99th percentile but without dynamic change; and (iv) patients with symptoms and high-sensitivity troponin >99th percentile and dynamic change but without coronary plaque rupture/erosion/dissection. Definitive evidence is currently lacking to manage these patients whose early diagnosis is 'indeterminate' and these areas of uncertainty should be assigned a high priority for research.
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| 11. |
- Lindholm, Carl-Johan, et al.
(author)
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Experimental analysis of stresses in curved sandwich structures
- 2015
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In: 20th International Conference on Composite Materials.
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Conference paper (other academic/artistic)abstract
- Some studies indicate that the cross-section of large wind turbine blades subjected to wind and gravity loads will ovalise due to the Brazier effects [1,2]. This feature could however not be verified by numerical experiments of a FE model of a fictive 61.5 m blade, based on the NREL 5MW reference turbine [3], subjected to simplified load cases. Accurate prediction of failure modes of sandwich structures based on finite element calculations are highly important if accurate predictions of such features in large wind turbine blades are to be investigated.In this study, an experimental setup designed to cause deflection and stress patterns in the core similar to what might be achieved by the Brazier effect in a wind turbine blade subjected to severe wind loads has been carried out. The test set up will highlight stress in the through-thickness direction, causing classical shell theory to be circumspect as a modelling tool. By designing specimens with different foam core material properties, stiffness and strength, different failure modes were observed in the test. Through the use of combinations of solid and shell elements and geometrically nonlinear analyses, the experimental effects were shown to be predictable by an otherwise linear FE model.
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| 12. |
- Lindholm, Carl-Johan, et al.
(author)
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Experimental analysis of stresses in sandwich structures due to the brazier effect
- 2015
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In: ICCM International Conferences on Composite Materials. ; 2015-July
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Conference paper (peer-reviewed)abstract
- © 2015 International Committee on Composite Materials. All rights reserved. Some studies indicate that the cross-section of large wind turbine blades subjected to wind and gravity loads will ovalise due to the Brazier effects [1,2]. This feature could however not be verified by numerical experiments of a FE model of a fictive 61.5 m blade, based on the NREL 5MW reference turbine [3], subjected to simplified load cases. Accurate prediction of failure modes of sandwich structures based on finite element calculations are highly important if accurate predictions of such features in large wind turbine blades are to be investigated. In this study, an experimental setup designed to cause deflection and stress patterns in the core similar to what might be achieved by the Brazier effect in a wind turbine blade subjected to severe wind loads has been carried out. The test set up will highlight stress in the through-thickness direction, causing classical shell theory to be circumspect as a modelling tool. By designing specimens with different foam core material properties, stiffness and strength, different failure modes were observed in the test. Through the use of combinations of solid and shell elements and geometrically nonlinear analyses, the experimental effects were shown to be predictable by an otherwise linear FE model.
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| 13. |
- Lindholm, Daniel, 1982-, et al.
(author)
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Bioimpedance and New-Onset Heart Failure : A Longitudinal Study of >500 000 Individuals From the General Population.
- 2018
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In: Journal of the American Heart Association. - 2047-9980. ; 7:13
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Journal article (peer-reviewed)abstract
- BACKGROUND: Heart failure constitutes a high burden on patients and society, but although lifetime risk is high, it is difficult to predict without costly or invasive testing. We aimed to establish new risk factors of heart failure, which potentially could enable early diagnosis and preemptive treatment.METHODS AND RESULTS: We applied machine learning in the UK Biobank in an agnostic search of risk factors for heart failure in 500 451 individuals, excluding individuals with prior heart failure. Novel factors were then subjected to several in-depth analyses, including multivariable Cox models of incident heart failure, and assessment of discrimination and calibration. Machine learning confirmed many known and putative risk factors for heart failure and identified several novel candidates. Mean reticulocyte volume appeared as one novel factor and leg bioimpedance another, the latter appearing as the most important new marker. Leg bioimpedance was lower in those who developed heart failure during an up to 9.8-year follow-up. When adjusting for known heart failure risk factors, leg bioimpedance was inversely related to heart failure (hazard ratio [95% confidence interval], 0.60 [0.48-0.73] and 0.75 [0.59-0.94], in age- and sex-adjusted and fully adjusted models, respectively, comparing the upper versus lower quartile). A model including leg bioimpedance, age, sex, and self-reported history of myocardial infarction showed good discrimination for future heart failure hospitalization (Concordance index [C-index]=0.82) and good calibration.CONCLUSIONS: Leg bioimpedance is inversely associated with heart failure incidence in the general population. A simple model of exclusively noninvasive measures, combining leg bioimpedance with history of myocardial infarction, age, and sex provides accurate predictive capacity.
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| 14. |
- Lindholm, Daniel, 1982-, et al.
(author)
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Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease
- 2017
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In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 70:7, s. 813-826
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Journal article (peer-reviewed)abstract
- Background Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD).Objectives This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD.Methods In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study.Results During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This “ABC-CHD” model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts.Conclusions This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903)
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| 15. |
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| 16. |
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| 17. |
- Lindholm, Daniel P, 1982-, et al.
(author)
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Association of Multiple Biomarkers With Risk of All-Cause and Cause-Specific Mortality After Acute Coronary Syndromes : A Secondary Analysis of the PLATO Biomarker Study
- 2018
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In: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 3:12, s. 1160-1166
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Journal article (peer-reviewed)abstract
- Importance: Mortality remains at about 5% within a year after an acute coronary syndrome event. Prior studies have assessed biomarkers in relation to all-cause or cardiovascular deaths but not across multiple causes.Objective: To assess if different biomarkers provide information about the risk for all-cause and cause-specific mortality.Design, Setting, and Participants: The Platelet Inhibition and Patient Outcomes (PLATO) trial randomized 18 624 patients with acute coronary syndrome to ticagrelor or clopidogrel from October 2006 through July 2008. In this secondary analysis biomarker substudy, 17 095 patients participated.Main Outcomes and Measures: Death due to myocardial infarction, heart failure, sudden cardiac death/arrhythmia, bleeding, procedures, other vascular causes, and nonvascular causes, as well as all-cause death.Exposures: At baseline, levels of cystatin-C, growth differentiation factor-15 (GDF-15), high-sensitivity C-reactive protein, high-sensitivity troponin I and T, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were determined.Results: The median (interquartile range) age of patients was 62.0 (54.0-71.0) years. Of 17 095 patients, 782 (4.6%) died during follow-up. The continuous associations between biomarkers and all-cause and cause-specific mortality were modeled using Cox models and presented as hazard ratio (HR) comparing the upper vs lower quartile. For all-cause mortality, NT-proBNP and GDF-15 were the strongest markers with adjusted HRs of 2.96 (95% CI, 2.33-3.76) and 2.65 (95% CI, 2.17-3.24), respectively. Concerning death due to heart failure, NT-proBNP was associated with an 8-fold and C-reactive protein, GDF-15, and cystatin-C, with a 3-fold increase in risk. Regarding sudden cardiac death/arrhythmia, NT-proBNP was associated with a 4-fold increased risk and GDF-15 with a doubling in risk. Growth differentiation factor-15 had the strongest associations with other vascular and nonvascular deaths and was possibly associated with death due to major bleeding (HR, 4.91; 95% CI, 1.39-17.43).Conclusions and Relevance: In patients with acute coronary syndrome, baseline levels of NT-proBNP and GDF-15 were strong markers associated with all-cause death based on their associations with death due to heart failure as well as due to arrhythmia and sudden cardiac death. Growth differentiation factor-15 had the strongest associations with death due to other vascular or nonvascular causes and possibly with death due to bleeding.Trial Registration: ClinicalTrials.gov Identifier: NCT00391872.
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| 18. |
- Lindholm, Daniel P, 1982-, et al.
(author)
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Growth Differentiation Factor 15 at 1 Month After an Acute Coronary Syndrome Is Associated With Increased Risk of Major Bleeding.
- 2017
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In: Journal of the American Heart Association. - 2047-9980. ; 6:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Growth differentiation factor-15 (GDF-15) is related to major bleeding when measured at initial presentation in patients with acute coronary syndromes (ACSs) treated with dual antiplatelet therapy. It is unknown whether follow-up measurements provide additional information. The objective of this study was to investigate whether GDF-15 measured 1 month after an ACS provides additional information beyond the baseline levels with regard to the risk of major bleeding.METHODS AND RESULTS: GDF-15 was measured at baseline and at 1 month after an ACS in 4049 patients included in the PLATelet inhibition and patient Outcomes (PLATO) trial. The association between 1-month GDF-15 level and non-coronary artery bypass grafting surgery-related major bleeding was assessed by a multivariable Cox model, adjusting for baseline GDF-15, age, anemia, impaired renal function, history of gastrointestinal bleeding, and sex. Elevated GDF-15 (>1800 ng/L) at 1 month was associated with an increased risk of non-coronary artery bypass grafting-related major bleeding (3.9% versus 1.2%; hazard ratio, 3.38; 95% CI, 1.89-6.06), independent of baseline GDF-15. Patients who had elevated GDF-15 levels at baseline and subsequent nonelevated GDF-15 at 1 month had a similar risk as patients who had nonelevated levels at both measurements.CONCLUSIONS: GDF-15 at 1 month after an ACS is related to the risk of bleeding during DAPT and provides additional information on the bleeding risk beyond baseline GDF-15 levels. GDF-15 levels may therefore be useful as part of decision support concerning long-term antithrombotic treatment in patients post-ACS.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
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| 19. |
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| 20. |
- Lindholm, Daniel, 1982-
(author)
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Platelet Inhibition, Revascularization, and Risk Prediction in Non-ST-elevation Acute Coronary Syndromes
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Cardiovascular disease is the leading cause of death worldwide and ischemic heart disease is the most common manifestation. Despite improved outcomes during the last decades, patients with acute coronary syndromes (ACS) are still at substantial risk of recurrent ischemic events and mortality.The aims of this thesis were to investigate the effect of the novel antiplatelet agent ticagrelor versus clopidogrel in patients with non-ST-elevation ACS (NSTE-ACS), overall and in relation to initial revascularization, and to explore this effect in relation to cardiac biomarkers. The impact of timing of revascularization in non-ST-elevation myocardial infarction (NSTEMI) was also studied, by assessing risk of mortality and recurrent myocardial infarction in relation to delay of percutaneous coronary intervention (PCI) in a nation-wide cohort. Finally, a novel clinical prediction model based on angiographic findings, biomarkers, and clinical characteristics was developed to estimate risk of ischemic events after performed revascularization.Ticagrelor treatment compared with clopidogrel was associated with a reduction in the composite endpoint of cardiovascular death/myocardial infarction/stroke and mortality alone, without any increase in overall major bleeding, but increased non-CABG-related major bleeding. The effect of ticagrelor over clopidogrel was consistent independent of initial revascularization. Elevated high-sensitivity cardiac troponin-T predicted benefit of ticagrelor over clopidogrel, while no difference between treatments was detected at normal levels. In patients with NSTEMI, PCI treatment within two days after hospital admission was associated with lower risk of all-cause death and recurrent myocardial infarction compared with delayed PCI. The new clinical prediction model included the following variables: prior vascular disease, extent of coronary artery disease, level of N-terminal pro-B-type natriuretic peptide and estimated glomerular filtration rate; and showed good discriminatory ability for the risk prediction of cardiovascular death/myocardial infarction/stroke and cardiovascular death alone.In conclusion, these results show that ticagrelor reduces the risk of recurrent ischemic events and mortality in patients with NSTE-ACS when compared with clopidogrel, and this effect seems independent of performed revascularization. The results also indicate that biomarkers could be used to select patients who would benefit most from more intense platelet inhibition. Furthermore, early PCI in NSTEMI seems to be associated with improved outcome. Finally, the novel clinical prediction model based only on four variables showed good discriminatory ability, which makes it a potentially effective and simple tool for tailored treatment based on individual risk of recurrent events.
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| 21. |
- Rao, Abhiram S, et al.
(author)
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Large-Scale Phenome-Wide Association Study of PCSK9 Variants Demonstrates Protection Against Ischemic Stroke.
- 2018
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In: Circulation. - 2574-8300. ; 11:7
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Journal article (peer-reviewed)abstract
- BACKGROUND: PCSK9 inhibition is a potent new therapy for hypercholesterolemia and cardiovascular disease. Although short-term clinical trial results have not demonstrated major adverse effects, long-term data will not be available for some time. Genetic studies in large biobanks offer a unique opportunity to predict drug effects and provide context for the evaluation of future clinical trial outcomes.METHODS: We tested the association of the PCSK9 missense variant rs11591147 with predefined phenotypes and phenome-wide, in 337 536 individuals of British ancestry in the UK Biobank, with independent discovery and replication. Using a Bayesian statistical method, we leveraged phenotype correlations to evaluate the phenome-wide impact of PCSK9 inhibition with higher power at a finer resolution.RESULTS: The T allele of rs11591147 showed a protective effect on hyperlipidemia (odds ratio, 0.63±0.04; P=2.32×10-38), coronary heart disease (odds ratio, 0.73±0.09; P=1.05×10-6), and ischemic stroke (odds ratio, 0.61±0.18; P=2.40×10-3) and was associated with increased type 2 diabetes mellitus risk adjusted for lipid-lowering medication status (odds ratio, 1.24±0.10; P=1.98×10-7). We did not observe associations with cataracts, heart failure, atrial fibrillation, and cognitive dysfunction. Leveraging phenotype correlations, we observed evidence of a protective association with cerebral infarction and vascular occlusion. These results explore the effects of direct PCSK9 inhibition; off-target effects cannot be predicted using this approach.CONCLUSIONS: This result represents the first genetic evidence in a large cohort for the protective effect of PCSK9 inhibition on ischemic stroke and corroborates exploratory evidence from clinical trials. PCSK9 inhibition was not associated with variables other than those related to LDL (low-density lipoprotein) cholesterol, atherosclerosis, and type 2 diabetes mellitus, suggesting that other effects are either small or absent.
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| 22. |
- Sarno, Giovanna, et al.
(author)
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Real-life clinical outcomes with everolimus eluting platinum chromium stent with an abluminal biodegradable polymer in patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
- 2017
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In: Catheterization and cardiovascular interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 90:6, s. 881-887
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Journal article (peer-reviewed)abstract
- BACKGROUND: No previous studies have evaluated the performance of the Synergy stent in a large real-life population.OBJECTIVES: To describe the initial real-life experience with a novel everolimus eluting platinum chromium stent with abluminal biodegradable polymer (SYNERGY) in unselected patients from a nationwide registry.METHODS: All implanted Synergy stents were compared with other new generation drug eluting stents (n-DES) with >1,000 implantations in Sweden between March 2013 and October 2015. Restenosis, definite stent thrombosis (ST), myocardial infarction (MI) and death rates were assessed using propensity score and Cox regression analyses.RESULTS: A total of 7,886 of Synergy stents and 64,429 other n-DES (BioMatrix, N = 1,953; Orsiro, N = 4,946; Promus Element Plus, N= 2,543; Promus Premier, N= 20,414; Xience Xpedition, N= 7,971, Resolute/Resolute Integrity, N = 19,021; Ultimaster, N = 1,156; Resolute Onyx, N = 6,425) were implanted in 42,357 procedures. Restenosis and stent thrombosis occurred in 642 and 314 cases, respectively, in the overall population at 1 year. The cumulative rate of restenosis (1.1% vs. 1.0%, adjusted HR: 1.24 95% CI: 0.88-1.75; P = 0.21) and ST (0.4% vs. 0.5%, adjusted HR: 0.97; 95% CI: 0.63-1.50; P = 0.17) up to 1 year was low in both the Synergy group and the other n-DES group. Death occurred in 5.2% versus 4.5% (adjusted HR: 1.14; 95% CI: 0.96-1.36; P = 0.11) and MI in 3.2% versus 3.5%, (adjusted HR: 1.11; 95% CI: 0.93-1.33; P = 0.24) up to 1 year.CONCLUSIONS: In a large real-life population the Synergy stent appears to be safe and effective with a low rate of restenosis and ST comparable with other n-DES.
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