| 1. |
- Wain, Louise V., et al.
(författare)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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| 2. |
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| 3. |
- Damman, Peter, et al.
(författare)
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Treatment Patterns and Outcomes in Patients Undergoing Percutaneous Coronary Intervention Treated With Prasugrel or Clopidogrel (from the Swedish Coronary Angiography and Angioplasty Registry [SCAAR])
- 2014
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 113:1, s. 64-69
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Tidskriftsartikel (refereegranskat)abstract
- Large real-world registry data are important for understanding the current use and outcomes of novel therapies. The aim of this study was to assess treatment patterns and outcomes in patients who underwent percutaneous coronary intervention (PCI) with prasugrel or clopidogrel. Consecutive patient data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for 2010 and 2011 were used. The study population consisted of all patients with acute coronary syndromes (ACS) and those without ACS who underwent PCI and were treated with prasugrel (with or without a clopidogrel loading dose) or solely with clopidogrel. Outcomes included were 30-day mortality and in-hospital bleeding. In 2010 and 2011, 23,994 patients were treated with clopidogrel during hospitalization for their first PCI during the study period, while 2,142 patients were treated with prasugrel. Prasugrel was mainly used in patients with ST-segment elevation myocardial infarction. Hemorrhagic risk factors such as older age, female gender, and previous stroke were more common in the clopidogrel-treated patients. However, Mehran bleeding risk scores were higher in prasugrel-treated patients. In the ACS group, lower mortality was observed in the prasugrel group compared with the clopidogrel group. Mortality was comparable in patients who underwent elective angiography and PCI. In-hospital bleeding was lower in prasugrel-treated patients. In conclusion, in this real world population of patients who underwent urgent or elective PCI, prasugrel was used mainly in patients with ACS, while it was avoided in patients with characteristics indicating increased bleeding risk. Mortality and bleeding rates were lower with prasugrel than clopidogrel, probably because of patient selection.
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| 4. |
- Alfredsson, Joakim, et al.
(författare)
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Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes
- 2014
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 168:4, s. 522-529
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Tidskriftsartikel (refereegranskat)abstract
- Background A routine invasive (RI) strategy in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been associated with better outcome compared with a selective invasive (SI) strategy in men, but results in women have yielded disparate results. The aim of this study was to assess gender differences in long-term outcome with an SI compared with an RI strategy in NSTE ACS. Methods Individual patient data were obtained from the FRISC II trial, ICTUS trial, and RITA 3 trial for a collaborative meta-analysis. Results Men treated with an RI strategy had significantly lower rate of the primary outcome 5-year cardiovascular (CV) death/myocardial infarction (MI) compared with men treated with an SI strategy (15.6% vs 19.8%, P = .001); risk-adjusted hazards ratio (HR) 0.73 (95% CI 0.63-0.86). In contrast, there was little impact of an RI compared with an SI strategy on the primary outcome among women (16.5% vs 15.1%, P = .324); risk-adjusted HR 1.13 (95% CI 0.89-1.43), interaction P = .01. For the individual components of the primary outcome, a similar pattern was seen with lower rate of MI (adjusted HR 0.69, 95% CI 0.57-0.83) and CV death (adjusted HR 0.71, 95% CI 0.56-0.89) in men but without obvious difference in women in MI (adjusted HR 1.13, 95% CI 0.85-1.50) or CV death (adjusted HR 0.97, 95% CI 0.68-1.39). Conclusions In this meta-analysis comparing an SI and RI strategy, benefit from an RI strategy during long-term follow-up was confirmed in men. Conversely, in women, there was no evidence of benefit.
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| 5. |
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| 6. |
- Damman, Peter, et al.
(författare)
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Invasive strategies and outcomes for non-ST-segment elevation acute coronary syndromes : a twelve-year experience from SWEDEHEART.
- 2016
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Ingår i: EuroIntervention. - 1774-024X .- 1969-6213. ; 12:9, s. 1108-1116
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Despite recommendations in recent guidelines for a routine invasive strategy for non-ST-segment elevation acute coronary syndrome (NSTE-ACS), long-term data on the implementation of treatment strategies in clinical practice are not available. Our aim was to provide long-term data on the implementation of a routine invasive strategy in NSTE-ACS in clinical practice.METHODS AND RESULTS: In the SWEDEHEART registry, data from 204,092 consecutive NSTE-ACS patients admitted between 1996 and 2007 were recorded. The use of the routine invasive strategy, retrospectively defined as coronary angiography (and subsequent revascularisation) within three days after admission, increased from 3.8% in the period 1996-1998 to 37.4% in the period 2005-2007. The largest absolute increase in the use of this strategy was observed in low-risk patients, while a similar relative increase was observed in all risk categories. The use of the selective invasive strategy, defined as coronary angiography later than three days after admission or none at all, decreased from 96.2% in the period 1996-1998 to 62.5% in the period 2005-2007. In the total population, there was a gradual decrease in three-year all-cause mortality, from 29.1% in the period 1996-1998 to 23.9% in the period 2005-2007.CONCLUSIONS: There has been an increase in the use of a routine invasive strategy in NSTE-ACS patients over the course of 12 years in Sweden. There was a decrease in three-year mortality over the same time course.
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| 9. |
- Damman, Peter, et al.
(författare)
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Long-Term Cardiovascular Mortality after Procedure-Related or Spontaneous Myocardial Infarction in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome : A Collaborative Analysis of Individual Patient Data from the FRISC II, ICTUS, and RITA-3 Trials (FIR)
- 2012
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 125:4, s. 568-576
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To investigate the long-term prognostic impact of procedure-related and spontaneous myocardial infarction (MI) on cardiovascular mortality in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS AND RESULTS: Five-year follow-up after procedure-related or spontaneous MI was investigated in the individual patient-pooled dataset of the FRISC-II, ICTUS and RITA-3 (FIR) NSTE-ACS trials. The principal outcome was cardiovascular death up to 5 years of follow-up. Cumulative event rates were estimated with the Kaplan-Meier method, hazard ratios (HR) were calculated with time-dependent Cox proportional-hazards models. Adjustments were made for the variables associated with long-term outcomes. Of the 5467 patients, 212 endured a procedure-related MI within 6 months after enrolment. A spontaneous MI occurred in 236 patients within 6 months. The cumulative cardiovascular death rate was 5.2% in patients who endured a procedure-related MI and comparable to patients without a procedure-related MI (HR 0.66, 95%CI: 0.36-1.20, P=0.17). In patients who endured a spontaneous MI within 6 months, the cumulative cardiovascular death rate was 22.2% and higher than patients without a spontaneous MI (HR 4.52, 95%CI: 3.37-6.06, P<0.001). These HRs did not materially alter after risk adjustments. CONCLUSIONS: Five-year follow-up of NSTE-ACS patients from the three FIR trials showed no association between a procedure-related MI and long-term cardiovascular mortality. In contrast there was a substantially raised long-term mortality after a spontaneous MI.
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| 10. |
- Damman, Peter, et al.
(författare)
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P2Y12 platelet inhibition in clinical practice
- 2012
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 33:2, s. 143-153
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Tidskriftsartikel (refereegranskat)abstract
- Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines.
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