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| 2. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
- Brilakis, Emmanouil S., et al.
(författare)
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Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery : Insights from the PLATelet inhibition and patient outcomes (PLATO) trial
- 2013
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 166:3, s. 474-480
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG. Methods Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression. Results Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P-interaction = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P-interaction =.46) prior CABG. Conclusions Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.
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| 5. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 6. |
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| 7. |
- Franchi, Francesco, et al.
(författare)
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Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y12 Receptor Antagonist Effects in Patients With Acute Coronary Syndromes : Insights From the PLATO Trial
- 2019
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P<0.001). Patients with DM+/CKD- and DM-/CKD+ had an intermediate risk profile. The same trend was shown for the individual components of the primary end point and for major bleeding. Compared with clopidogrel, ticagrelor reduced the incidence of the primary end point consistently across subgroups (P-interaction=0.264), but with an increased absolute risk reduction in DM+/CKD+. The effects on major bleeding were also consistent across subgroups (P-interaction=0.288). Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.
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| 8. |
- Haiman, Christopher A., et al.
(författare)
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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:12, s. 61-1210
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
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| 9. |
- Held, Claes, 1956-, et al.
(författare)
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Inflammatory Biomarkers Interleukin-6 and C-Reactive Protein and Outcomes in Stable Coronary Heart Disease : Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial
- 2017
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEvaluation of cardiovascular prognosis in patients with stable coronary heart disease is based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfunction, and possibly cardiac dysfunction. Inflammation plays a key role in atherosclerosis, but the association between inflammatory biomarkers and clinical outcomes is less studied in this population.Methods and ResultsOverall, 15 828 patients with coronary heart disease in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial werer and randomized to treatment with darapladib or placebo and observed for a median of 3.7 years. In 14 611 patients, levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein were measured in plasma samples: median levels were2.1 (interquartile range, 1.4-3.2) ng/Land1.3 (interquartile range, 0.6-3.1) mg/L, respectively. Associations between continuous levels or quartile groups and adjudicated outcomes were evaluated by spline graphs and Cox regression adjusted for clinical factors and cardiovascular biomarkers. IL-6 was associated with increased risk of major adverse cardiovascular events (quartile 4 versus quartile 1 hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.30-1.97; P< 0.0001); cardiovascular death (HR, 2.15; 95% CI, 1.53-3.04; P< 0.0001); myocardial infarction (HR, 1.53; 95% CI, 1.14-2.04; P< 0.05); all-cause mortality (HR, 2.11; 95% CI, 1.62-2.76; P< 0.0001); and risk of hospitalization for heart failure (HR, 2.28; 95% CI, 1.34-3.89; P< 0.001). Cancer death was doubled in the highest IL-6 quartile group (HR, 2.34; 95% CI, 1.20-4.53; P< 0.05). High-sensitivity C-reactive protein was associated with both cardiovascular and non-cardiovascular events in the unadjusted model, but these did not remain after multivariable adjustments.ConclusionsIL-6, an upstream inflammatory marker, was independently associated with the risk of major adverse cardiovascular events, cardiovascular and all-cause mortality, myocardial infarction, heart failure, and cancer mortality in patients with stable coronary heart disease. IL-6 might reflect a pathophysiological process involved in the development of these events.
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| 10. |
- Kotsia, Anna, et al.
(författare)
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Extent of coronary artery disease and outcomes after ticagrelor administration in patients with an acute coronary syndrome : Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
- 2014
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 168:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Background Extensive coronary artery disease (CAD) is associated with higher risk. In this substudy of the PLATO trial, we examined the effects of randomized treatment on outcome events and safety in relation to the extent of CAD. Methods Patients were classified according to presence of extensive CAD (defined as 3-vessel disease, left main disease, or prior coronary artery bypass graft surgery). The trial's primary and secondary end points were compared using Cox proportional hazards regression. Results Among 15,388 study patients for whom the extent of CAD was known, 4,646 (30%) had extensive CAD. Patients with extensive CAD had more high-risk characteristics and experienced more clinical events during follow-up. They were less likely to undergo percutaneous coronary intervention (58% vs 79%, P < .001) but more likely to undergo coronary artery bypass graft surgery (16% vs 2%, P < .001). Ticagrelor, compared with clopidogrel, reduced the composite of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD (14.9% vs 17.6%, hazard ratio [HR] 0.85 [0.73-0.98]) similar to its reduction in those without extensive CAD (6.8% vs 8.0%, HR 0.85 [0.74-0.98], P-interaction = .99). Major bleeding was similar with ticagrelor vs clopidogrel among patients with (25.7% vs 25.5%, HR 1.02 [0.90-1.15]) and without (7.3% vs 6.4%, HR 1.14 [0.98-1.33], P-interaction = .24) extensive CAD. Conclusions Patients with extensive CAD have higher rates of recurrent cardiovascular events and bleeding. Ticagrelor reduced ischemic events to a similar extent both in patients with and without extensive CAD, with bleeding rates similar to clopidogrel.
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| 11. |
- Lindholm, Daniel P, et al.
(författare)
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Biomarkers and Coronary Lesions Predict Outcomes after Revascularization in Non-ST-Elevation Acute Coronary Syndrome
- 2017
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 63:2, s. 573-584
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Risk stratification in non-ST-elevation acute coronary syndrome (NSTE-ACS) is currently mainly based on clinical characteristics. With routine invasive management, angiography findings and biomarkers are available and may improve prognostication. We aimed to assess if adding biomarkers [high-sensitivity cardiac troponin T (cTnT-hs), N-terminal probrain-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15)] and extent of coronary artery disease (CAD) might improve prognostication in revascularized patients with NSTE-ACS.METHODS: In the PLATO (Platelet Inhibition and Patient Outcomes) trial, 5174 NSTE-ACS patients underwent initial angiography and revascularization and had cTnT-hs, NT-proBNP, and GDF-15 measured. Cox models were developed adding extent of CAD and biomarker levels to established clinical risk variables for the composite of cardiovascular death (CVD)/spontaneous myocardial infarction (MI), and CVD alone. Models were compared using c-statistic and net reclassification improvement (NRI).RESULTS: For the composite end point and CVD, prognostication improved when adding extent of CAD, NT-proBNP, and GDF-15 to clinical variables (c-statistic 0.685 and 0.805, respectively, for full model vs 0.649 and 0.760 for clinical model). cTnT-hs did not contribute to prognostication. In the full model (clinical variables, extent of CAD, all biomarkers), hazard ratios (95% CI) per standard deviation increase were for cTnT-hs 0.93(0.81-1.05), NT-proBNP 1.32(1.13-1.53), GDF-15 1.20(1.07-1.36) for the composite end point, driven by prediction of CVD by NT-proBNP and GDF-15. For spontaneous MI, there was an association with NT-proBNP or GDF-15, but not with cTnT-hs.CONCLUSIONS: In revascularized patients with NSTE-ACS, the extent of CAD and concentrations of NT-proBNP and GDF-15 independently improve prognostication of CVD/spontaneous MI and CVD alone. This information may be useful for selection of patients who might benefit from more intense and/or prolonged antithrombotic treatment.
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| 12. |
- Purrington, Kristen S., et al.
(författare)
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Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer
- 2014
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:5, s. 1012-1019
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Tidskriftsartikel (refereegranskat)abstract
- In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
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| 13. |
- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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| 14. |
- Steg, Philippe Gabriel, et al.
(författare)
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Ticagrelor Versus Clopidogrel in Patients With ST-Elevation Acute Coronary Syndromes Intended for Reperfusion With Primary Percutaneous Coronary Intervention A Platelet Inhibition and Patient Outcomes (PLATO) Trial Subgroup Analysis
- 2010
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 122:21, s. 2131-2141
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Tidskriftsartikel (refereegranskat)abstract
- Background-Aspirin and clopidogrel are recommended for patients with acute coronary syndromes (ACS) or undergoing coronary stenting. Ticagrelor, a reversible oral P2Y12-receptor antagonist, provides faster, greater, and more consistent platelet inhibition than clopidogrel and may be useful for patients with acute ST-segment elevation (STE) ACS and planned primary percutaneous coronary intervention. Methods and Result-Platelet Inhibition and Patient Outcomes (PLATO), a randomized, double-blind trial, compared ticagrelor with clopidogrel for the prevention of vascular events in 18 624 ACS patients. This report concerns the 7544 ACS patients with STE or left bundle-branch block allocated to either ticagrelor 180-mg loading dose followed by 90 mg twice daily or clopidogrel 300-mg loading dose (with provision for 300 mg clopidogrel at percutaneous coronary intervention) followed by 75 mg daily for 6 to 12 months. The reduction of the primary end point (myocardial infarction, stroke, or cardiovascular death) with ticagrelor versus clopidogrel (10.8% versus 9.4%; hazard ratio [HR], 0.87; 95% confidence interval, 0.75 to 1.01; P=0.07) was consistent with the overall PLATO results. There was no interaction between presentation with STE/left bundle-branch block and randomized treatment (interaction P=0.29). Ticagrelor reduced several secondary end points, including myocardial infarction alone (HR, 0.80; P=0.03), total mortality (HR, 0.82; P=0.05), and definite stent thrombosis (HR, 0.66; P=0.03). The risk of stroke, low in both groups, was higher with ticagrelor (1.7% versus 1.0%; HR, 1.63; 95% confidence interval, 1.07 to 2.48; P=0.02). Ticagrelor did not affect major bleeding (HR, 0.98; P=0.76). Conclusion-In patients with STE-ACS and planned primary percutaneous coronary intervention, the effects of ticagrelor were consistent with those observed in the overall PLATO trial.
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| 15. |
- Stevens, Kristen N, et al.
(författare)
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19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
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Tidskriftsartikel (refereegranskat)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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| 16. |
- Stevens, Kristen N., et al.
(författare)
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Common Breast Cancer Susceptibility Loci Are Associated with Triple-Negative Breast Cancer
- 2011
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Ingår i: Cancer Research. - 1538-7445. ; 71:19, s. 6240-6249
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Tidskriftsartikel (refereegranskat)abstract
- Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240-9. (C)2011 AACR.
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| 17. |
- Tangelder, Marco J. D., et al.
(författare)
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Effect of ximelagatran on ischemic events and death in patients with atrial fibrillation after acute myocardial infarction in the efficacy and safety of the oral direct thrombin inhibitor ximelagatran in patients with recent myocardial damage (ESTEEM) trial
- 2008
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 155:2, s. 382-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: New-onset trial fibrillation (AF) occurs commonly after acute myocardial infarction (MI) and is associated with a poor prognosis due to stroke or death. The optimal antithrombotic therapy is unknown. The aim of this study was to investigate whether an oral direct thrombin inhibitor, ximelagatran, added to aspirin, reduced the risk of death, myocardial infarction (MI), and stroke in patients who developed AF after their qualifying MI in the efficacy and safety of the oral direct thrombin inhibitor ximelagatran in patients with recent myocardial damage (ESTEEM) trial. METHODS: The ESTEEM trial evaluated 6 months treatment with ximelagatran together with aspirin, compared to aspirin alone, for prevention of ischemic events in 1883 patients randomized within 14 days after an MI. After their qualifying MI, 174 (9%) patients developed AF in hospital. Multivariate hazard ratios for ximelagatran compared with placebo were calculated by presence AF. RESULTS: Of 101 patients with AF treated with ximelagatran 7 (6.9%) had either death, MI, or stroke, compared with 15 (20.6%) in 73 patients allocated to placebo. Ximelagatran reduced the risk of death, MI, or stroke by 70% (hazard ratio 0.30, 95% CI 0.12-0.74). For the separate outcome events, we found similar, nonsignificant trends. One major bleeding event occurred in each treatment group. CONCLUSIONS: For patients with MI complicated by AF, the combination of aspirin and an oral direct thrombin inhibitor seems beneficial. The high risk for death, MI, and stroke in this population and the increasing use of percutaneous interventions in MI patients may suggest a combination of long-term antiplatelet and anticoagulant therapy. Randomized clinical trials are warranted.
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| 22. |
- White, Harvey D, et al.
(författare)
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Darapladib for preventing ischemic events in stable coronary heart disease
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 370:18, s. 1702-1711
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2.METHODS:In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization).RESULTS:During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02).CONCLUSIONS:In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).
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| 23. |
- White, Harvey D., et al.
(författare)
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Survival with Cardiac-Resynchronization Therapy in Mild Heart Failure
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 370:18, s. 1702-1711
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated lipoprotein-associated phospholipase A(2) activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A(2). Methods: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). Results: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). ConclusionsIn patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.)
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| 24. |
- Åkerblom, Axel, et al.
(författare)
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Interleukin-18 in patients with acute coronary syndromes.
- 2019
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:12, s. 1202-1209
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to assess associations between circulating IL-18 concentrations and cardiovascular outcomes in patients with acute coronary syndromes (ACS).HYPOTHESIS AND METHODS: Plasma IL-18 concentrations were measured at admission, discharge, 1 month, and 6 months in patients with ACS in the PLATelet inhibition and patient Outcomes (PLATO) trial. Associations with outcomes were evaluated with Cox regression models on the composite of CV death, spontaneous myocardial infarction (sMI), or stroke; and on CV death or sMI separately, including adjustment for clinical risk factors and biomarkers (cTnT-hs, NT-proBNP, cystatin C, CRP-hs, and GDF-15).RESULTS: Median IL-18 concentrations at baseline, discharge, 1 month, and 6 months were 237, 283, 305, and 320 ng/L (n = 16 636). Male sex, obesity, diabetes, and plasma levels of cystatin C, GDF-15, and CRP-hs were independently associated with higher IL-18 levels. Higher baseline IL-18 levels were associated with the composite endpoint and with CV death (hazard ratio [HR] 1.05, 95% confidence interval [95% CI] 1.02-1.07 and HR 1.10, 95% CI 1.06-1.14, respectively, per 25% increase of IL-18 levels). Associations remained significant after adjustment for clinical variables but became non-significant after adjustment for all biomarkers (HR 1.01, 95% CI 0.98-1.04 and HR 1.04, 95% CI 1.00-1.08, respectively). There were no associations with sMI.CONCLUSIONS: In ACS patients, IL-18 concentrations increased after the acute event and remained increased for 6 months. Baseline IL-18 levels were significantly associated with CV mortality, independent of clinical characteristics and indicators of renal/cardiac dysfunction but this association was attenuated after adjustment for multiple biomarkers.
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| 25. |
- Niemi, MEK, et al.
(författare)
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- 2021
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