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- Emerging Risk Factors, Collaboration, et al.
(författare)
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The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases
- 2007
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Ingår i: Eur J Epidemiol. - 0393-2990. ; 22:12, s. 839-69
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Tidskriftsartikel (refereegranskat)abstract
- Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
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| 2. |
- Danesh, John, et al.
(författare)
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Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis
- 2005
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 294:14, s. 1799-1809
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Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.
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| 4. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Novel cerebrospinal fluid biomarkers of axonal degeneration in frontotemporal dementia.
- 2008
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Ingår i: Molecular medicine reports. - : Spandidos Publications. - 1791-2997. ; 1:5, s. 757-61
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a heterogeneous disease with substantial interpersonal variance in aggressiveness. Novel biomarkers for rapidly progressive FTD could improve diagnosis and provide clues regarding its pathogenesis. In this study, surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) was used to analyze peptide profiles in cerebrospinal fluid (CSF) from 24 FTD patients. Thirteen patients had rapidly progressive FTD with distinct pathology in a brain MRI after less than 3 years of disease duration. Eleven patients had slowly progressive FTD with a normal brain MRI, but had abnormal findings in SPECT/PET after more than 5 years of disease duration. The axonal damage marker CSF neurofilament light-chain (NF-L) was measured in all subjects to evaluate the amount of axonal degeneration. A CSF NF-L level of 150 ng/l was used as a cut-off point for high NF-L expression. SELDI-TOF analysis of peptides in the range of 2000-20000 m/z revealed one peak with m/z of 6378 that was expressed at a significantly different level (p<0.01) when rapidly versus slowly progressive cases of FTD were compared. Eleven peaks were expressed at different levels when high versus low CSF NF-L were compared. Using chromatographic purification followed by tandem mass spectrometric analysis, five of these peaks were identified as follows: C-terminal fragment of neuroendocrine protein 7B2 (3512.84 Da), C-terminal fragment of osteopontin (7658.19 Da) as well as its mono- and diphosphorylated forms (7738.16 Da and 7818.13 Da, respectively) and pancreatic ribonuclease (14566.33 Da). The peak intensity of pancreatic ribonuclease was higher in patients with low NF-L expression, while the other peptides had a lower peak intensity in this group. Altered levels of these peptides have also been described in other neurodegenerative diseases. Taken together, these data suggest that differentially-expressed peptides are general markers of axonal degeneration. Further studies are needed to verify their prognostic value in FTD.
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| 6. |
- Nicholls, Ian A., et al.
(författare)
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Theoretical and Computational Strategies for Rational Molecularly Imprinted Polymer Design
- 2009
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Ingår i: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 25:3, s. 543-552
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Tidskriftsartikel (refereegranskat)abstract
- The further evolution of molecularly imprinted polymer science and technology necessitates the development of robust predictive tools capable of handling the complexity of molecular imprinting systems. A combination of the rapid growth in computer power over the past decade and significant software developments have opened new possibilities for simulating aspects of the complex molecular imprinting process. We present here a survey of the current status of the use of in silico-based approaches to aspects of molecular imprinting. Finally, we highlight areas where ongoing and future efforts should yield information critical to our understanding of the underlying mechanisms sufficient to permit the rational design of molecularly imprinted polymers.
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| 7. |
- Rosengren, Annika, 1951, et al.
(författare)
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Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey
- 2006
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Ingår i: Eur Heart J. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:7, s. 789-95
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Age is one of the most powerful determinants of prognosis in myocardial infarction, but there is comparatively little recent data across the whole spectrum of acute coronary syndromes (ACS). We examined the impact of increasing age on clinical presentation and hospital outcome in a large sample of patients with ACS. METHODS AND RESULTS: Patients (n = 10 253) from the Euroheart ACS survey in 103 hospitals in 25 countries were investigated. There was a significant inverse association between the age and the likelihood of presenting with ST-elevation. For each decade of life, the odds of presenting with ST-elevation decreased by 0.82 [95% confidence interval (CI) 0.79-0.84]; P < 0.0001. Elderly patients were considerably less often treated by cardiologists, less extensively investigated, and, when presenting with ST-elevation ACS, less likely to be treated with reperfusion. Compared with patients <55 years, the odds ratios of hospital mortality were 1.87 (1.21-2.88) at age 55-64, 3.70 (2.51-5.44) at age 65-74, 6.23 (4.25-9.14) at age 75-84, and 14.5 (9.47-22.1) among patients > or =85 years, with no major differences across different types of admission or discharge diagnoses. CONCLUSION: Elderly ACS patients were less likely to present with ST-elevation but had substantial in-hospital mortality, yet they were markedly less intensively treated and investigated.
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| 8. |
- Rosengren, Annika, 1951, et al.
(författare)
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Cardiovascular risk factors and clinical presentation in acute coronary syndromes
- 2005
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Ingår i: Heart. - : BMJ. - 1468-201X .- 1355-6037. ; 91:9, s. 1141-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the hypothesis that risk factors may be differently related to severity of acute coronary syndromes (ACS), with ST elevation used as a marker of severe ACS. DESIGN: Cross sectional study of patients with ACS. SETTING: 103 hospitals in 25 countries in Europe and the Mediterranean basin. PATIENTS: 10,253 patients with a discharge diagnosis of ACS in the Euro heart survey of ACS. MAIN OUTCOME MEASURES: Presenting with ST elevation ACS. RESULTS: Patients with ACS who were smokers had an increased risk to present with ST elevation (age adjusted odds ratio (OR) 1.84, 95% confidence interval (CI) 1.67 to 2.02). Hypertension (OR 0.65, 95% CI 0.60 to 0.70) and high body mass index (BMI) (p for trend 0.0005) were associated with less ST elevation ACS. Diabetes mellitus was also associated with less ST elevation, but only among men. Prior disease (infarction, chronic angina, revascularisation) and treatment with aspirin, beta blockers, or statins before admission were also associated with less ST elevation. After adjustment for age, sex, prior disease, and prior medication, smoking was still significantly associated with increased risk of ST elevation (OR 1.53, 95% CI 1.38 to 1.69), whereas hypertension was associated with reduced risk (OR 0.75, 95% CI 0.69 to 0.82). Obesity (BMI > 30 kg/m2 versus < 25 kg/m2) was independently associated with less risk of presenting with ST elevation among women, but not among men. CONCLUSION: Among patients with ACS, presenting with ST elevation is strongly associated with smoking, whereas hypertension and high BMI (in women) are associated with less ST elevation, independently of prior disease and medication.
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