| 1. |
- Franceschini, N., et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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| 2. |
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| 3. |
- 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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| 4. |
- 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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| 5. |
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| 6. |
- den Ruijter, H. M., et al.
(författare)
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Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 56:7, s. 1494-1502
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.
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| 7. |
- Franceschini, N, et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5141-
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Tidskriftsartikel (refereegranskat)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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| 8. |
- Lorenz, M. W., et al.
(författare)
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Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration
- 2018
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
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| 9. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 10. |
- Di Angelantonio, E., et al.
(författare)
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Association of Cardiometabolic Multimorbidity With Mortality
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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| 11. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 12. |
- Fowkes, F. G. R., et al.
(författare)
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Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events
- 2014
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 21:3, s. 310-320
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Tidskriftsartikel (refereegranskat)abstract
- Background The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. Design An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. Methods Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events. Results In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women. Conclusions An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.
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| 13. |
- Pischon, T., et al.
(författare)
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General and Abdominal Adiposity and Risk of Death in Europe
- 2008
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 359:20, s. 2105-2120
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. METHODS We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. RESULTS During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% confidence interval [CI], 1.80 to 2.33) and 1.78 (95% CI, 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI, 1.53 to 1.84) and 1.51 (95% CI, 1.37 to 1.66), respectively. BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P<0.001). CONCLUSIONS These data suggest that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-tohip ratio in addition to BMI in assessing the risk of death.
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| 14. |
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| 15. |
- Rohrmann, S., et al.
(författare)
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The association of education with long-term weight change in the EPIC-PANACEA cohort
- 2012
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:8, s. 957-963
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Cross-sectionally, educational attainment is strongly associated with the prevalence of obesity, but this association is less clear for weight change during adult life. The objective of this study is to examine the association between educational attainment and weight change during adult life in the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS/METHODS: EPIC is a cohort study with 361 467 participants and up to 10 years of follow-up. Educational attainment was categorized according to the highest obtained school level (primary school or less, vocational secondary training, other secondary education and university). Multivariate mixed-effects linear regression models were used to study education in relation to weight at age 20 years (self-reported), to annual change in weight between age 20 years and measured weight at recruitment, and to annual change in weight during follow-up time. RESULTS: Higher educational attainment was associated with on average a lower body mass index (BMI) at age 20 years and a lower increase in weight up to recruitment (highest vs lowest educational attainment in men: -60 g per year (95% confidence interval (CI) -80; -40), women -110 g per year (95% CI -130; -80)). Although during follow-up after recruitment an increase in body weight was observed in all educational levels, gain was lowest in men and women with a university degree (high vs low education -120 g per year (95% CI -150; -90) and -70 g per year (95% CI -90; -60), respectively). CONCLUSIONS: Existing differences in BMI between higher and lower educated individuals at early adulthood became more pronounced during lifetime, which possibly impacts on obesity-related chronic disease risk in persons with lower educational attainment.
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| 16. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 17. |
- Wang, X., et al.
(författare)
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Clustering of cardiovascular risk factors and carotid intima-media thickness: The USE-IMT study
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Background The relation of a single risk factor with atherosclerosis is established. Clinically we know of risk factor clustering within individuals. Yet, studies into the magnitude of the relation of risk factor clusters with atherosclerosis are limited. Here, we assessed that relation. Individual participant data from 14 cohorts, involving 59,025 individuals were used in this cross-sectional analysis. We made 15 clusters of four risk factors (current smoking, overweight, elevated blood pressure, elevated total cholesterol). Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) between clusters using those without any of the four risk factors as reference group. Compared to the reference, those with 1, 2, 3 or 4 risk factors had a significantly higher common CIMT: mean difference of 0.026 mm, 0.052 mm, 0.074 mm and 0.114 mm, respectively. These findings were the same in men and in women, and across ethnic groups. Within each risk factor cluster (1, 2, 3 risk factors), groups with elevated blood pressure had the largest CIMT and those with elevated cholesterol the lowest CIMT, a pattern similar for men and women. Clusters of risk factors relate to increased common CIMT in a graded manner, similar in men, women and across race-ethnic groups. Some clusters seemed more atherogenic than others. Our findings support the notion that cardiovascular prevention should focus on sets of risk factors rather than individual levels alone, but may prioritize within clusters.
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| 18. |
- Bots, Michiel L., et al.
(författare)
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Common Carotid Intima-Media Thickness Measurements Do Not Improve Cardiovascular Risk Prediction in Individuals With Elevated Blood Pressure The USE-IMT Collaboration
- 2014
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Ingår i: Hypertension. - 1524-4563. ; 63:6, s. 1173-1181
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Tidskriftsartikel (refereegranskat)abstract
- Carotid intima-media thickness (CIMT) is a marker of cardiovascular risk. It is unclear whether measurement of mean common CIMT improves 10-year risk prediction of first-time myocardial infarction or stroke in individuals with elevated blood pressure. We performed an analysis among individuals with elevated blood pressure (ie, a systolic blood pressure 140 mm Hg and a diastolic blood pressure 90 mm Hg) in USE-IMT, a large ongoing individual participant data meta-analysis. We refitted the risk factors of the Framingham Risk Score on asymptomatic individuals (baseline model) and expanded this model with mean common CIMT (CIMT model) measurements. From both models, 10-year risks to develop a myocardial infarction or stroke were estimated. In individuals with elevated blood pressure, we compared discrimination and calibration of the 2 models and calculated the net reclassification improvement (NRI). We included 17 254 individuals with elevated blood pressure from 16 studies. During a median follow-up of 9.9 years, 2014 first-time myocardial infarctions or strokes occurred. The C-statistics of the baseline and CIMT models were similar (0.73). NRI with the addition of mean common CIMT was small and not significant (1.4%; 95% confidence intervals, -1.1 to 3.7). In those at intermediate risk (n=5008, 10-year absolute risk of 10% to 20%), the NRI was 5.6% (95% confidence intervals, 1.6-10.4). There is no added value of measurement of mean common CIMT in individuals with elevated blood pressure for improving cardiovascular risk prediction. For those at intermediate risk, the addition of mean common CIMT to an existing cardiovascular risk score is small but statistically significant.
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| 19. |
- Crowe, F. L., et al.
(författare)
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Dietary fibre intake and ischaemic heart disease mortality : the European Prospective Investigation into Cancer and Nutrition-Heart study
- 2012
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:8, s. 950-956
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Evidence from prospective studies is consistent in showing an inverse association between dietary fibre intake and risk of ischaemic heart disease (IHD), but whether dietary fibre from various food sources differ in their effect on IHD risk is less clear. The objective of this study was to assess the associations of total and food sources of dietary fibre with IHD mortality in the European Prospective Investigation into Cancer and Nutrition-Heart study. SUBJECTS/METHODS: Participants were 306 331 men and women from eight European countries. Dietary fibre intake was assessed using centre or country-specific diet questionnaires and calibrated using a 24-h diet recall. RESULTS: After an average follow-up of 11.5 years, there were 2381 IHD deaths among participants without cardiovascular disease at baseline. The calibrated intake of dietary fibre was inversely related with IHD mortality; each 10 g/day was associated with a 15% lower risk (relative risk (RR) 0.85; 95% confidence interval (CI): 0.73-0.99, P = 0.031). There was no difference in the associations of the individual food sources of dietary fibre with the risk of IHD mortality; RR for each 5 g/day higher cereal fibre intake was 0.91 (CI: 0.82-1.01), RR for each 2.5 g/day fruit fibre intake was 0.94 (CI: 0.88-1.01) and RR for each 2.5 g/day vegetable fibre intake was 0.90 (95% CI: 0.76-1.07). CONCLUSION: A higher consumption of dietary fibre is associated with a lower risk of fatal IHD with no clear difference in the association with IHD for fibre from cereals, fruits or vegetables.
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| 20. |
- Di Angelantonio, Emanuele, et al.
(författare)
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Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration
- 2015
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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| 21. |
- Eikendal, Anouk L M, et al.
(författare)
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Common Carotid Intima-Media Thickness Relates to Cardiovascular Events in Adults Aged
- 2015
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Ingår i: Hypertension. - 1524-4563. ; 65:4, s. 707-707
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Tidskriftsartikel (refereegranskat)abstract
- Although atherosclerosis starts in early life, evidence on risk factors and atherosclerosis in individuals aged <45 years is scarce. Therefore, we studied the relationship between risk factors, common carotid intima-media thickness (CIMT), and first-time cardiovascular events in adults aged <45 years. Our study population consisted of 3067 adults aged <45 years free from symptomatic cardiovascular disease at baseline, derived from 6 cohorts that are part of the USE-IMT initiative, an individual participant data meta-analysis of general-population-based cohort studies evaluating CIMT measurements. Information on risk factors, CIMT measurements, and follow-up of the combined end point (first-time myocardial infarction or stroke) was obtained. We assessed the relationship between risk factors and CIMT and the relationship between CIMT and first-time myocardial infarction or stroke using a multivariable linear mixed-effects model and a Cox proportional-hazards model, respectively. During a follow-up of 16.3 years, 55 first-time myocardial infarctions or strokes occurred. Median CIMT was 0.63 mm. Of the risk factors under study, age, sex, diastolic blood pressure, body mass index, total cholesterol, and high-density lipoprotein cholesterol related to CIMT. Furthermore, CIMT related to first-time myocardial infarction or stroke with a hazard ratio of 1.40 per SD increase in CIMT, independent of risk factors (95% confidence interval, 1.11-1.76). CIMT may be a valuable marker for cardiovascular risk in adults aged <45 years who are not yet eligible for standard cardiovascular risk screening. This is especially relevant in those with an increased, unfavor-able risk factor burden.
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| 22. |
- Gijsberts, Crystel M, et al.
(författare)
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Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.
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| 23. |
- Sonkoly, E, et al.
(författare)
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MicroRNA-203 functions as a tumor suppressor in basal cell carcinoma.
- 2012
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Basal cell carcinoma (BCC) of the skin represents the most common malignancy in humans. MicroRNAs (miRNAs), small regulatory RNAs with pleiotropic function, are commonly misregulated in cancer. Here we identify miR-203, a miRNA abundantly and preferentially expressed in skin, to be downregulated in BCCs. We show that activation of the Hedgehog (HH) pathway, critically involved in the pathogenesis of BCCs, as well as the EGFR/MEK/ERK/c-JUN signaling pathway suppresses miR-203. We identify c-JUN, a key effector of the HH pathway, as a novel direct target for miR-203 in vivo. Further supporting the role of miR-203 as a tumor suppressor, in vivo delivery of miR-203 mimics in a BCC mouse model results in the reduction of tumor growth. Our results identify a regulatory circuit involving miR-203 and c-JUN, which provides functional control over basal cell proliferation and differentiation. We propose that miR-203 functions as a 'bona fide' tumor suppressor in BCC, whose suppressed expression contributes to oncogenic transformation via derepression of multiple stemness- and proliferation-related genes, and its overexpression could be of therapeutic value.
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| 24. |
- Den Ruijter, Hester M., et al.
(författare)
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Common Carotid Intima-Media Thickness Measurements in Cardiovascular Risk Prediction A Meta-analysis
- 2012
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 308:8, s. 796-803
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Tidskriftsartikel (refereegranskat)abstract
- Context The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent. Objective To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score. Data Sources Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion. Study Selection Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke. Data Extraction Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease. Results We included 14 population-based cohorts contributing data for 45 828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women. Conclusion The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance. JAMA. 2012;308(8):796-803 www.jama.com
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| 25. |
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| 26. |
- Britton, Annie R, et al.
(författare)
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Alcohol consumption and common carotid intima-media thickness : The USE-IMT study
- 2017
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 52:4, s. 483-486
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of early atherosclerosis in the general population. Methods: Individual participant data from eight cohorts, involving 37,494 individuals from the USE-IMT collaboration were used. Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) with alcohol consumption. Results: The mean age was 57.9 years (SD 8.6) and the mean CIMT was 0.75 mm (SD 0.177). About, 40.5% reported no alcohol consumed, and among those who drank, mean consumption was 13.3 g per day (SD 16.4). Those consuming no alcohol or a very small amount (<5 g per day) had significantly lower common CIMT values than those consuming >10 g per day, after adjusting for a range of confounding factors. Conclusion: In this large CIMT consortium, we did not find evidence to support a protective effect of alcohol on CIMT.
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| 27. |
- Fedorowski, Artur, et al.
(författare)
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Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium.
- 2012
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:18, s. 2331-2341
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown.Methods and resultsA total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8%) met the diagnostic criteria for OH (systolic/diastolic BP drop ≥20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85-0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75-0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87-0.98; P= 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.02-1.24; P = 0.02, rs198358: 1.10, 1.01-1.20; P = 0.04, and rs5068: 1.22, 1.04-1.43; P = 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P= 0.04).ConclusionThe overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components.
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| 28. |
- Kathiresan, Sekar, et al.
(författare)
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Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
- 2008
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 189-97
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Tidskriftsartikel (refereegranskat)abstract
- Blood concentrations of lipoproteins and lipids are heritable risk factors for cardiovascular disease. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 x 10(-8) for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.
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| 29. |
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| 30. |
- May, Anne M., et al.
(författare)
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Determinants of non- response to a second assessment of lifestyle factors and body weight in the EPIC-PANACEA study
- 2012
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Ingår i: BMC Medical Research Methodology. - : BioMed Central. - 1471-2288. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: This paper discusses whether baseline demographic, socio-economic, health variables, length of follow-up and method of contacting the participants predict non-response to the invitation for a second assessment of lifestyle factors and body weight in the European multi-center EPIC-PANACEA study. Methods: Over 500.000 participants from several centers in ten European countries recruited between 1992 and 2000 were contacted 2-11 years later to update data on lifestyle and body weight. Length of follow-up as well as the method of approaching differed between the collaborating study centers. Non-responders were compared with responders using multivariate logistic regression analyses. Results: Overall response for the second assessment was high (81.6%). Compared to postal surveys, centers where the participants completed the questionnaire by phone attained a higher response. Response was also high in centers with a short follow-up period. Non-response was higher in participants who were male (odds ratio 1.09 (confidence interval 1.07; 1.11), aged under 40 years (1.96 (1.90; 2.02), living alone (1.40 (1.37; 1.43), less educated (1.35 (1.12; 1.19), of poorer health (1.33 (1.27; 1.39), reporting an unhealthy lifestyle and who had either a low (<18.5 kg/m2, 1.16 (1.09; 1.23)) or a high BMI (>25, 1.08 (1.06; 1.10); especially >= 30 kg/m2, 1.26 (1.23; 1.29)). Conclusions: Cohort studies may enhance cohort maintenance by paying particular attention to the subgroups that are most unlikely to respond and by an active recruitment strategy using telephone interviews.
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| 31. |
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| 32. |
- Borné, Yan, et al.
(författare)
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Complement C3 Associates With Incidence of Diabetes, but No Evidence of a Causal Relationship
- 2017
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 102:12, s. 4477-4485
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study explored whether complement factor 3 (C3) in plasma is associated with incidence of diabetes in a population-based cohort. We also identified genetic variants related to C3 and explored whether C3 and diabetes share common genetic determinants.Methods: C3 was analyzed in plasma from 4368 nondiabetic subjects, 46 to 68 years old, from the Malmö Diet and Cancer Study. Incidence of diabetes was studied in relationship to C3 levels during 17.7± 4.4 years of follow-up. Genotypes associated with C3 were identified in a genome-wide association study. Diabetes Genetics Replication and Meta-Analysis and the European Genetic Database were used for in silico look-up.Results: In all, 538 (12.3%) subjects developed diabetes during 18 years of follow-up. High C3 was significantly associated with incidence of diabetes after risk factor adjustments (hazard ratio comparing 4th vs 1st quartile, 1.54 (95% confidence interval, 1.13 to 2.09; P = 0.005). C3 was associated with polymorphisms at the complement factor H locus (P < 10-8). However, no relationship with diabetes was observed for this locus. Another eight loci were associated with C3 with P < 10-5. One of them, the glucose kinase regulatory protein (GCKR) locus, has been previously associated with diabetes. The relationship between C3 levels and the GCKR locus was replicated in the European Genetic Database cohort.Conclusions: Plasma concentration of C3 is a risk marker for incidence of diabetes. The results suggest that this association could, in part, be explained by pleiotropic effects related to the GCKR gene.
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| 33. |
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| 34. |
- Chambers, John C., et al.
(författare)
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Genetic loci influencing kidney function and chronic kidney disease
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 373-375
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Tidskriftsartikel (refereegranskat)abstract
- Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.
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| 35. |
- Enhörning, Sofia, et al.
(författare)
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Copeptin, a marker of vasopressin, in abdominal obesity, diabetes and microalbuminuria: the prospective Malmö Diet and Cancer Study cardiovascular cohort.
- 2013
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 37:4, s. 598-603
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Tidskriftsartikel (refereegranskat)abstract
- Background: High plasma copeptin (copeptin), the C-terminal fragment of arginine vasopressin pro-hormone, has been associated with the metabolic syndrome (MetS), diabetes mellitus (DM) development and nephropathy. Here we tested whether elevated copeptin level is associated with later development of the MetS, its individual components and microalbuminuria. Methods: We analysed copeptin at baseline (1991-1994) in the population-based Malmö Diet and Cancer Study cardiovasular cohort and re-examined 2064 subjects 15.8 years later (mean age 72.8 years, 59% women) with oral glucose tolerance test and measurement of MetS and its individual components. Results: After age and sex adjustment, increasing quartiles of copeptin at baseline (the lowest quartile as reference) were associated with MetS (P for trend=0.008), incident abdominal obesity (P for trend=0.002), DM (P for trend=0.001) and microalbuminuria (P for trend=0.002). After additional adjustment for all the MetS components at baseline, increasing copeptin quartiles predicted incident abdominal obesity (odds ratios 1.55, 1.30 and 1.59; P for trend=0.04), DM (odds ratios 1.18, 1.32 and 1.46; P for trend=0.04) and microalbuminuria (odds ratios 1.05, 1.08 and 1.65; P for trend=0.02) but not MetS (P for trend=0.19) at the reexamination. Further, the relationship between copeptin and microalbuminuria was independent of baseline C-reactive protein, incident DM and incident hypertension. Conclusion: Copeptin independently predicts DM and abdominal obesity but not the cluster of MetS. Apart from predicting DM and abdominal obesity, elevated copeptin signals increased risk of microalbuminuria. Interestingly, the association between copeptin and later microalbuminuria was independent of both prevalent and incident DM and hypertension. Our findings suggest a relationship between a dysregulated vasopressin system and cardiometabolic risk, which could have implications for risk assessment and novel preventive treatments.
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| 36. |
- Gertow, Karl, et al.
(författare)
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Identification of the BCAR1-CFDP1-TMEM170A Locus as a Determinant of Carotid Intima-Media Thickness and Coronary Artery Disease Risk
- 2012
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X .- 1942-3268. ; 5:6, s. 656-665
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Tidskriftsartikel (refereegranskat)abstract
- Background-Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse. Methods and Results-To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMTmean, IMTmax, and IMTmean-max), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11 590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75x10(-7) for IMTmax; replication P=7.24x10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53x10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83x10(-4), n= 82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138). Conclusions-This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent. (Circ Cardiovasc Genet. 2012;5:656-665.)
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| 37. |
- Jansson, Jan-Håkan, et al.
(författare)
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Snus (Swedish smokeless tobacco) use and risk of stroke: pooled analyses of incidence and survival
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 276:1, s. 87-95
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Tidskriftsartikel (refereegranskat)abstract
- Background. Snus is a moist smokeless tobacco product with high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear. Objective. The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes. Methods. Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130 485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively. Results. No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) amongst users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61). Conclusion. Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared with nonusers, but further studies are needed to determine any possible causal mechanisms.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Padmanabhan, Sandosh, et al.
(författare)
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Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
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| 43. |
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| 44. |
- Steffen, Annika, et al.
(författare)
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Development and Validation of a Risk Score Predicting Substantial Weight Gain over 5 Years in Middle-Aged European Men and Women
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identifying individuals at high risk of excess weight gain may help targeting prevention efforts at those at risk of various metabolic diseases associated with weight gain. Our aim was to develop a risk score to identify these individuals and validate it in an external population. Methods: We used lifestyle and nutritional data from 53 degrees 758 individuals followed for a median of 5.4 years from six centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) to develop a risk score to predict substantial weight gain (SWG) for the next 5 years (derivation sample). Assuming linear weight gain, SWG was defined as gaining >= 10% of baseline weight during follow-up. Proportional hazards models were used to identify significant predictors of SWG separately by EPIC center. Regression coefficients of predictors were pooled using random-effects meta-analysis. Pooled coefficients were used to assign weights to each predictor. The risk score was calculated as a linear combination of the predictors. External validity of the score was evaluated in nine other centers of the EPIC study (validation sample). Results: Our final model included age, sex, baseline weight, level of education, baseline smoking, sports activity, alcohol use, and intake of six food groups. The model's discriminatory ability measured by the area under a receiver operating characteristic curve was 0.64 (95% CI = 0.63-0.65) in the derivation sample and 0.57 (95% CI = 0.56-0.58) in the validation sample, with variation between centers. Positive and negative predictive values for the optimal cut-off value of >= 200 points were 9% and 96%, respectively. Conclusion: The present risk score confidently excluded a large proportion of individuals from being at any appreciable risk to develop SWG within the next 5 years. Future studies, however, may attempt to further refine the positive prediction of the score.
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| 45. |
- Wiegleb Edström, Desirée, 1959-, et al.
(författare)
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Flashlamp pulsed dye laser and argon-pumped dye laser in the treatment of port-wine stains a clinical and histological comparison
- 2002
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Ingår i: British Journal of Dermatology. - : Wiley-Blackwell Publishing Inc.. - 0007-0963 .- 1365-2133. ; 146:2, s. 285-289
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Port-wine stains (PWS) are congenital vascular malformations occurring in 0.3% of children. The pulsed dye laser is a well established treatment for PWS.OBJECTIVES: To compare, clinically and histologically, the effects of the flashlamp pulsed dye laser with the argon-pumped dye laser in the treatment of PWS.METHODS: Thirty patients were treated on two to four test areas with both laser types using different energy fluences. A flashlamp pulsed dye laser with 0.45 ms pulse duration and a spot size of 5 mm was compared with an argon-pumped dye laser, with a spot size of 1 mm delivered with a robotic scanning laser handpiece (Hexascan) and 70-190 ms pulse duration. Both were tuned to 585 nm. Twelve weeks later the degree of lightening was evaluated and biopsies were taken. To count the vessels the skin sections were stained with CD34 using an immunohistochemical technique. The vessels were divided into three groups by diameter (d): d < 10 microm, 10 < or = d < 20 microm, d > or = 20 microm.RESULTS: The clinical results showed a significantly better lightening using the flashlamp pulsed dye laser than with the argon-pumped dye laser. The histological results showed a significant decrease in the number of vessels of diameter larger than 20 microm in treated compared with untreated lesions. We found no histological difference in the number of vessels between the two laser treatments. However, there was a tendency towards more small vessels (diameter < 10 microm) after one treatment with the flashlamp pulsed dye laser compared with untreated PWS.CONCLUSIONS: The flashlamp pulsed dye laser is clinically superior to the argon-pumped dye laser in the treatment of PWS.
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| 46. |
- Adamsson Eryd, Samuel, et al.
(författare)
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Red blood cell distribution width is associated with incidence of atrial fibrillation.
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 275:1, s. 84-92
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Tidskriftsartikel (refereegranskat)abstract
- Red blood cell distribution width (RDW), a measure of variation in erythrocyte volume, has been associated with several cardiovascular disorders, but the relationship with atrial fibrillation (AF) remains unclear. We investigated the association between RDW and incidence of first hospitalization due to AF in a population-based cohort.
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| 47. |
- Andersson, Eva M., 1968, et al.
(författare)
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Partial Mediation by Cadmium Exposure of the Association Between Tobacco Smoking and Atherosclerotic Plaques in the Carotid Artery
- 2018
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 187:4, s. 806-816
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to cadmium confers increased cardiovascular risk. Tobacco smoke contains cadmium, which, hypothetically, may mediate parts of the tobacco-associated risk of developing atherosclerotic plaques. Baseline data from the Swedish Malmo Diet and Cancer cohort (1991-1996) were used to test this hypothesis. Mediation analysis was used to examine associations between smoking and blood cadmium levels and the prevalence of ultrasound-assessed carotid atherosclerotic plaques. The total association with smoking status (never smokers, 2 categories of former smokers, and current smokers) was split into direct and indirect association, and the proportion mediated was estimated. The adjusted estimated plaque prevalence was approximately 27% among never smokers. We identified both a direct and an indirect pathway between smoking and carotid plaques; the indirect association, through cadmium, was observed among current smokers and former smokers who had quit smoking less than 15 years before. For current smokers, the prevalence ratio for plaque was 1.5, with 60%-65% of the association with smoking being mediated through cadmium. Recent former smokers had a prevalence ratio of 1.3, and 40%-45% was mediated through cadmium. Long-time former smokers had a prevalence ratio of 1.2, but none of the association was mediated through cadmium. In conclusion, about two-thirds of the proatherosclerotic association with smoking was mediated by cadmium.
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| 48. |
- Berntsson, John, et al.
(författare)
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Pro-atrial natriuretic peptide and prediction of atrial fibrillation and stroke : The Malmö Preventive Project
- 2017
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 24:8, s. 788-795
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Tidskriftsartikel (refereegranskat)abstract
- Background The increasing prevalence of atrial fibrillation and novel therapeutic tools to prevent cardioembolic stroke has increased the need for risk markers. Objectives This study explored the relationship between the midregional sequence of pro-atrial natriuretic peptide (MR-proANP) levels with the risk of atrial fibrillation and stroke, and whether measurement of MR-proANP improves the prediction of these outcomes. Methods MR-proANP was measured in fasting blood samples of 5130 subjects (69% men, mean age 69.2 ± 6.2 years) without a history of atrial fibrillation or stroke from the general population. The incidence of atrial fibrillation and stroke was monitored over a median follow-up of 5.6 years. C-statistics and net reclassification improvement was used to assess the predictive ability of MR-proANP in addition to conventional risk factors. Results Log-normalized MR-proANP was significantly associated with the incidence of atrial fibrillation (n = 362; hazard ratio (HR); 95% confidence interval (CI) per 1 standard deviation (SD) 2.05, 1.86-2.27) and stroke from all causes (n = 195; HR 1.30; 95% CI 1.12-1.50). The HR for stroke events related to atrial fibrillation was 1.79 (95% CI 1.25-2.58) per 1 SD. MR-proANP significantly improved the prediction of atrial fibrillation when added to a risk score of conventional risk factors (C statistic 0.69 vs. 0.75), mainly by down-classifying subjects who did not develop atrial fibrillation. A smaller improvement in predictive ability was observed for stroke (C statistic 0.66 vs. 0.68). Conclusion High plasma levels of MR-proANP are associated with the incidence of atrial fibrillation and stroke in the middle-aged and elderly population. MR-proANP may be useful to identify individuals with an increased risk of atrial fibrillation.
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