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Buccheri, S., Sarno, G., Frobert, O., Gudnason, T., Lagerqvist, B., Lindholm, D. P., . . . James, S. (2019). Assessing the Nationwide Impact of a Registry-Based Randomized Clinical Trial on Cardiovascular Practice The TASTE Trial in Perspective. Circulation. Cardiovascular Interventions, 12(3), Article ID e007381.
Open this publication in new window or tab >>Assessing the Nationwide Impact of a Registry-Based Randomized Clinical Trial on Cardiovascular Practice The TASTE Trial in Perspective
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2019 (English)In: Circulation. Cardiovascular Interventions, ISSN 1941-7640, E-ISSN 1941-7632, Vol. 12, no 3, article id e007381Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
clinical trial, mortality, myocardial infarction, registry, thrombosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-387229 (URN)10.1161/CIRCINTERVENTIONS.118.007381 (DOI)000469353600004 ()30841711 (PubMedID)
Funder
Swedish Association of Local Authorities and Regions
Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-06-20Bibliographically approved
Patel, R. S., Schmidt, A. F., Tragante, V., McCubrey, R. O., Holmes, M. V., Howe, L. J., . . . Asselbergs, F. W. (2019). Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events: A GENIUS-CHD Study of Individual Participant Data. Circulation: Genomic and Precision Medicine, 12(4), Article ID e002471.
Open this publication in new window or tab >>Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events: A GENIUS-CHD Study of Individual Participant Data
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2019 (English)In: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, no 4, article id e002471Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
chromosome, genetic, variation, myocardial infarction, risk factor, secondary prevention
National Category
Cardiac and Cardiovascular Systems Medical Genetics
Identifiers
urn:nbn:se:uu:diva-383874 (URN)10.1161/CIRCGEN.119.002471 (DOI)000466741600005 ()30897348 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 201668EU, European Research Council, 294609EU, Horizon 2020, 01KL1802NIH (National Institute of Health)EU, Horizon 2020, 692145Wellcome trustEU, FP7, Seventh Framework Programme, 223004Forte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2019-06-14 Created: 2019-06-14 Last updated: 2019-06-14Bibliographically approved
Patel, R. S., Tragante, V., Schmidt, A. F., McCubrey, R. O., Holmes, M. V., Howe, L. J., . . . Asselbergs, F. W. (2019). Subsequent Event Risk in Individuals With Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium. Circulation: Genomic and Precision Medicine, 12(4), Article ID e002470.
Open this publication in new window or tab >>Subsequent Event Risk in Individuals With Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium
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2019 (English)In: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, no 4, article id e002470Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
coronary artery disease, genetics, myocardial infarction, prognosis, secondary prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-383875 (URN)10.1161/CIRCGEN.119.002470 (DOI)000466741600004 ()30896328 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 201668EU, FP7, Seventh Framework Programme, 305739EU, European Research Council, 294609Swedish Research CouncilSwedish Foundation for Strategic Research EU, European Research Council, 294609EU, Horizon 2020, 01KL1802NIH (National Institute of Health), R0133169NIH (National Institute of Health), R01ES021801NIH (National Institute of Health), R01MD010358NIH (National Institute of Health), R01ES025786NIH (National Institute of Health), R01HL103866NIH (National Institute of Health), R01DK106000NIH (National Institute of Health), R01HL126827NIH (National Institute of Health), P20HL113452NIH (National Institute of Health), P01HL098055NIH (National Institute of Health), P01HL076491NIH (National Institute of Health), R01HL103931NIH (National Institute of Health), AG051633NIH (National Institute of Health), 5P01HL101398-02NIH (National Institute of Health), 1P20HL113451-01NIH (National Institute of Health), 1R56HL126558-01NIH (National Institute of Health), 1RF-1AG051633-01NIH (National Institute of Health), R01 NS064162-01NIH (National Institute of Health), R01 HL89650-01NIH (National Institute of Health), HL095479-01NIH (National Institute of Health), 1U10HL110302-01NIH (National Institute of Health), 1DP3DK094346-01NIH (National Institute of Health), 2P01HL086773-06A1EU, Horizon 2020, 692145Wellcome trust, 072960/Z/03/ZWellcome trust, 084726/Z/08/ZWellcome trust, 084727/Z/08/ZWellcome trust, 085475/Z/08/ZWellcome trust, 085475/B/08/ZSwedish Heart Lung FoundationThe Crafoord FoundationKnut and Alice Wallenberg FoundationEU, FP7, Seventh Framework Programme, 223004Forte, Swedish Research Council for Health, Working Life and WelfareNIH (National Institute of Health), R01 NR013396
Available from: 2019-06-12 Created: 2019-06-12 Last updated: 2019-06-12Bibliographically approved
Lindholm, D. P., James, S. K., Gabrysch, K., Storey, R. F., Himmelmann, A., Cannon, C. P., . . . Wallentin, L. (2018). 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. JAMA cardiology, 3(12), 1160-1166
Open this publication in new window or tab >>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
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2018 (English)In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 3, no 12, p. 1160-1166Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-366806 (URN)10.1001/jamacardio.2018.3811 (DOI)000454036700007 ()30427997 (PubMedID)
Funder
AstraZeneca
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2019-01-25Bibliographically approved
Buccheri, S., Sarno, G., Lagerqvist, B., Olivecrona, G., Hambraeus, K., Witt, N., . . . James, S. K. (2018). Bioabsorbable polymer everolimus-eluting stents in patients with acute myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry.. EuroIntervention, 14(5), e562-e569
Open this publication in new window or tab >>Bioabsorbable polymer everolimus-eluting stents in patients with acute myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry.
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2018 (English)In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 14, no 5, p. e562-e569Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:uu:diva-355163 (URN)10.4244/EIJ-D-18-00392 (DOI)000440694800015 ()29792402 (PubMedID)
Funder
Swedish Association of Local Authorities and Regions
Available from: 2018-06-26 Created: 2018-06-26 Last updated: 2018-11-08Bibliographically approved
Lindholm, D., Fukaya, E., Leeper, N. J. & Ingelsson, E. (2018). Bioimpedance and New-Onset Heart Failure: A Longitudinal Study of >500 000 Individuals From the General Population.. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 7(13), Article ID e008970.
Open this publication in new window or tab >>Bioimpedance and New-Onset Heart Failure: A Longitudinal Study of >500 000 Individuals From the General Population.
2018 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 13, article id e008970Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
heart failure, machine learning, risk factors
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-355904 (URN)10.1161/JAHA.118.008970 (DOI)000452700100033 ()29959136 (PubMedID)
Available from: 2018-07-07 Created: 2018-07-07 Last updated: 2019-01-16Bibliographically approved
Lindholm, D., James, S. K., Andersson, J., Braun, O. Ö., Heller, S., Henriksson, P., . . . Varenhorst, C. (2018). Caffeine and incidence of dyspnea in patients treated with ticagrelor. American Heart Journal, 200, 141-143
Open this publication in new window or tab >>Caffeine and incidence of dyspnea in patients treated with ticagrelor
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2018 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 200, p. 141-143Article in journal (Refereed) Published
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:uu:diva-355162 (URN)10.1016/j.ahj.2018.02.011 (DOI)000434948300021 ()29898843 (PubMedID)
Available from: 2018-06-26 Created: 2018-06-26 Last updated: 2018-11-12Bibliographically approved
Fukaya, E., Flores, A. M., Lindholm, D. P., Gustafsson, S., Zanetti, D., Ingelsson, E. & Leeper, N. J. (2018). Clinical and Genetic Determinants of Varicose Veins Prospective, Community-Based Study of approximate to 500 000 Individuals. Circulation, 138(25), 2869-2880
Open this publication in new window or tab >>Clinical and Genetic Determinants of Varicose Veins Prospective, Community-Based Study of approximate to 500 000 Individuals
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2018 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, no 25, p. 2869-2880Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
epidemiology, genetics, genome-wide association study, varicose veins
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-374122 (URN)10.1161/CIRCULATIONAHA.118.035584 (DOI)000453713500067 ()30566020 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2013.0126
Available from: 2019-01-23 Created: 2019-01-23 Last updated: 2019-01-23Bibliographically approved
Rao, A. S., Lindholm, D., Rivas, M. A., Knowles, J. W., Montgomery, S. B. & Ingelsson, E. (2018). Large-Scale Phenome-Wide Association Study of PCSK9 Variants Demonstrates Protection Against Ischemic Stroke.. Circulation-genomic and precision medicine, 11(7), Article ID e002162.
Open this publication in new window or tab >>Large-Scale Phenome-Wide Association Study of PCSK9 Variants Demonstrates Protection Against Ischemic Stroke.
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2018 (English)In: Circulation-genomic and precision medicine, ISSN 2574-8300, Vol. 11, no 7, article id e002162Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
atrial fibrillation, diabetes mellitus, type 2, heart failure, humans, stroke
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-356106 (URN)10.1161/CIRCGEN.118.002162 (DOI)000447462400006 ()29997226 (PubMedID)
Available from: 2018-07-13 Created: 2018-07-13 Last updated: 2018-12-10Bibliographically approved
Lindholm, D. & Holzmann, M. (2018). Machine Learning For Improved Detection Of Myocardial Infarction In Patients Presenting With Chest Pain In The Emergency Department. Paper presented at 67th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), MAR 10-12, 2018, Orlando, FL, USA. Journal of the American College of Cardiology, 71(11), 225-225
Open this publication in new window or tab >>Machine Learning For Improved Detection Of Myocardial Infarction In Patients Presenting With Chest Pain In The Emergency Department
2018 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 71, no 11, p. 225-225Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-357328 (URN)10.1016/S0735-1097(18)30766-6 (DOI)000429659701075 ()
Conference
67th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), MAR 10-12, 2018, Orlando, FL, USA
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3526-0614

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