| 1. |
- 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. |
- Kaptoge, S., et al.
(författare)
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C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:14, s. 1310-1320
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Tidskriftsartikel (refereegranskat)abstract
- Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P < 0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (< 10%), " intermediate" (10% to < 20%), and "high" (>= 20%) (P < 0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of >= 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)
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| 5. |
- Wormser, David, et al.
(författare)
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Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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| 6. |
- Castaman, G., et al.
(författare)
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Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von Willebrand disease: an international, multicenter study
- 2006
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:10, s. 2164-2169
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We undertook an international, multicenter study to describe the clinical picture and to estimate the bleeding risk in a group of obligatory carriers of type 3 von Willebrand disease (VWD). Patients and methods: Obligatory carriers (OC) of type 3 VWD were identified by the presence of offspring with type 3 VWD or by being an offspring of a type 3 patient. Normal controls were age- and sex-matched with the obligatory carriers. A physician-administered standardized questionnaire was used to evaluate hemorrhagic symptoms at presentation. A score system ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion) was used to quantitate bleeding manifestations. Odds ratios were computed for each symptom. Results: Ten centers participated to the study, enrolling a total of 35 type 3 VWD families, with 70 OC. A total of 215 normal controls and 42 OC for type 1 VWD were also included. About 40% of type 3 OC had at least one bleeding symptom compared to 23% of normal controls and 81.8% of type 1 OC (P < 0.0001 by chi-squared test), showing that type 3 OC clearly represent a distinct population from type 1 OC. The clinical situations associated with an increase of bleeding risk in type 3 OC were epistaxis [odds ratio 3.6; 90% confidence intervals (CI) 1.84-21.5], cutaneous bleeding (odds ratio 5.5; 90% CI 2.5-14.1) and postsurgical bleeding (odds ratio 16.3; 90% CI 4.5-59). The severity of bleeding score correlated with the degree of factor (F) VIII reduction in plasma. Conclusions: OC for type 3 VWD represent a distinctive population from type 1 OC. These patients, however, present with more frequent bleeding symptoms in comparison to normal controls, especially in case of significantly low FVIII. Desmopressin and/or tranexamic acid might be useful to prevent or treat bleeding in these cases.
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| 7. |
- Castaman, G., et al.
(författare)
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Validation of a rapid test (VWF-LIA) for the quantitative determination of von Willebrand factor antigen in type 1 von Willebrand disease diagnosis within the European multicenter study MCMDM-1VWD
- 2010
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 126:3, s. 227-231
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurate measurement of von Willebrand factor (VWF) is a critical requirement for the diagnosis of von Willebrand disease (VWD). Aim of the study: To evaluate the diagnostic efficiency of a rapid quantitative test for the measurement of VWF antigen (VWF:Ag) in type 1 VWD. Patients and methods: VWF: Ag was measured with an ELISA in a robotic instrument, as a reference method, and with a fully automated latex-immunoassay (LIA) on an ACL 9000 analyser in 1,716 subjects enrolled within the Molecular and Clinical Markers for Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD) Study. Among these subjects, 1,049 were healthy controls, 281 healthy family members and 386 affected members from 127 European families with type 1 VWD. Results: The assay linearity range was 10-125 IU/dL for LIA (R-2 = 0.99) and 5-133 IU/dL for ELISA (R-2 = 0.99). The inter-assay CV for low VWF levels (similar to 30 IU/dL) was 2% for the LIA test and 8.7 % for ELISA. The sensitivity for detection of type 1 VWD affected members was 86% and the specificity 91% for LIA, 87% and 90% for ELISA. A receiver-operator (ROC) analysis disclosed only a marginal difference between the two tests, LIA having a slightly greater area under the curve (0.94 vs. 0.93, p = 0.03). Conclusion: VWF: Ag LIA compared well to standard ELISA in this large population of patients and controls, showing better CV. However the lower detection limit for the VWF: Ag LIA compared to the VWF: Ag ELISA means that the LIA assay is less good at discriminating between type 3 VWD and moderate type 1 VWD. (C) 2010 Elsevier Ltd. All rights reserved.
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| 8. |
- Lynch, Iseult, et al.
(författare)
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Correlation of the adhesive properties of cells to N-isopropylacrylamide/N-tert-butylacrylamide copolymer surfaces with changes in surface structure using contact angle measurements, molecular simulations, and Raman spectroscopy
- 2005
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 17:15, s. 3889-3898
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Tidskriftsartikel (refereegranskat)abstract
- A series of copolymers of N-isopropylacrylamide (NIPAM) and the more hydrophobic comonomer N-tert-butylacrylamide (NTBAM), with increasing NTBAM content (i.e., increasing hydrophobicity) were prepared. The adhesion of human epithelial cells on polymer films prepared from copolymers of NIPAM: NTBAM was observed to increase with increasing polymer hydrophobicity. However, in the absence of serum, cell adhesion to the different surfaces was statistically indistinguishable. Thus, it appears that the copolymer films differentially support cell adhesion due to selective adsorption of proteins from the physiological environment (the serum). Using contact angle measurements, molecular simulations, and Raman spectroscopy to characterize the different surfaces, we show evidence that the different behavior of cells on the films of increasing hydrophobicity is actually due to the different chemical properties of the surfaces with increasing content of NTBAM in the copolymers. As the NTBAM content is increased, the number of NH residues at the surface decreases, due to the additional steric hindrance of the bulkier NTBAM group, which results in decreased hydrogen bonding and thus decreased adsorption of proteins such as albumin. However, in some cases, the adsorption is driven by hydrophobic interactions, and proteins such as fibronectin were found to adsorb more to the films with a higher content of NTBAM. There appears, thus, to be a direct correlation between surface composition, i.e., the functional groups exposed at the surface, and protein binding and subsequent cell adhesion.
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| 9. |
- Rodeghiero, F, et al.
(författare)
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The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study
- 2005
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 3:12, s. 2619-2626
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was the validation of the criteria defining a significant mucocutaneous-bleeding history in type 1 von Willebrand disease (VWD). Subjects and methods: To avoid selection bias, 42 obligatory carriers (OC) of type 1 VWD were identified from a panel of 42 families with type 1 VWD enrolled by 10 expert centers. OC were identified by the presence of an offspring and another first degree relative with type 1 VWD (affected subjects, AFF). A standardized questionnaire was administered to evaluate hemorrhagic symptoms at the time of first examination, using a bleeding score ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion). Sensitivity, specificity, diagnostic likelihood ratios, positive and negative predictive values for the diagnosis of type 1 VWD were calculated from the data collected in OC and in 215 controls. Results: Having at least three hemorrhagic symptoms or a bleeding score of 3 in males and 5 in females was very specific (98.6%) for the bleeding history of type 1 VWD, although less sensitive (69.1%). None of the misclassified OC had life-threatening bleeding episodes after diagnosis. Conclusions: We suggest that the use of a standardized questionnaire and bleeding score may be useful for the identification of subjects requiring laboratory evaluation for VWD.
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| 10. |
- Tosetto, A., et al.
(författare)
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Impact of plasma von Willebrand factor levels in the diagnosis of type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1VWD)
- 2007
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 5:4, s. 715-721
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Tidskriftsartikel (refereegranskat)abstract
- Background: Presence of bleeding symptoms, inheritance and reduced von Willebrand factor (VWF) contribute to the diagnosis of type 1 von Willebrand disease (VWD). However, quantitative analysis of the importance of VWF antigen (VWF:Ag) and ristocetin cofactor activity (VWF:RCo) levels in the diagnosis is lacking. Objectives: To evaluate the relative contribution of VWF measurement to the diagnosis of VWD. Patients and methods: From the MCMDM-1VWD study cohort, 204 subjects (considered as affected by VWD based on the enrolling Center diagnoses and the presence of linkage with the VWF locus) were compared with 1155 normal individuals. Sensitivity, specificity and diagnostic positive likelihood ratios (LR) of VWF:Ag and VWF:RCo were computed. Results: ABO blood group was the variable most influencing VWF levels, but adjustment of the lower reference limit for the ABO group did not improve sensitivity and specificity of VWF:Ag or VWF:RCo. The lower reference limit (2.5th percentile) was 47 IU dL(-1) for both VWF:Ag and VWF:RCo and showed similar diagnostic performance [receiver-operator curve area: 0.962 and 0.961 for VWF:Ag and VWF:RCo, respectively; P = 0.81]. The probability of VWD was markedly increased only for values below 40 IU dL(-1) (positive LR: 95.1 for VWF:Ag), whereas intermediate values (40 to 60 IU dL(-1)) of VWF only marginally indicated the probability of VWD. Conclusions: Although the conventional 2.5 lower percentile has good sensitivity and specificity, only VWF:Ag or VWF:RCo values below 40 IU dL(-1) appear to significantly indicate the likelihood of type 1 VWD. The LR profile of VWF level could be used in a diagnostic algorithm.
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