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      Red Cell Distribution Width in Relation to Incidence of Stroke and Carotid Atherosclerosis: A Population-Based Cohort Study

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          Abstract

          Background

          Increased red cell distribution width (RDW) has been related to poor prognosis in patients with cardiovascular disease, and is a predictor of cardiovascular mortality in the general population. The purpose of the present study was to investigate if RDW is associated with increased incidence of stroke and its subtypes in individuals from the general population.

          Methods

          Red cell distribution width was measured in 26,879 participants (16,561 women and 10,318 men aged 45–73 years) without history of coronary events or stroke, from the population-based Malmö Diet and Cancer Study. Incidences of total stroke and stroke subtypes over a mean follow-up of 15.2 years were calculated in relation to sex-specific quartiles of RDW. The presence of carotid plaque and intima–media thickness, as assessed by ultrasound, was studied in relation to RDW in a randomly selected subcohort (n = 5,309).

          Results

          Incidences of total stroke (n = 1,869) and cerebral infarction (n = 1,544) were both increased in individuals with high RDW. Hazard ratios (HRs) in the highest compared to the lowest quartile were 1.31 for total stroke (95% confidence interval [CI]: 1.11–1.54, p for trend = 0.004) and 1.32 for cerebral infarction (95% CI: 1.10–1.58, p for trend = 0.004) after adjustment for stroke risk factors and hematological parameters. The adjusted HR for intracerebral hemorrhage (n = 230) was 1.44 (95% CI: 0.90–2.30) and the HR for subarachnoid hemorrhage (n = 75) was 0.94 (95% CI: 0.43–2.07), in the highest compared to the lowest quartile of RDW. Red cell distribution width was positively associated with intima–media thickness of the common carotid artery (p for trend = 0.011).

          Conclusions

          Red cell distribution width in the highest quartile was associated with increased incidence of total stroke and cerebral infarction. There was no significant association between RDW and incidence of intracerebral or subarachnoid hemorrhage.

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          Most cited references31

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          The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. WHO MONICA Project Principal Investigators.

          A World Health Organization Working Group has developed a major international collaborative study with the objective of measuring over 10 years, and in many different populations, the trends in, and determinants of, cardiovascular disease. Specifically the programme focuses on trends in event rates for validated fatal and non-fatal coronary heart attacks and strokes, and on trends in cardiovascular risk factors (blood pressure, cigarette smoking and serum cholesterol) in men and women aged 25-64 in the same defined communities. By this means it is hoped both to measure changes in cardiovascular mortality and to see how far they are explained; on the one hand by changes in incidence mediated by risk factor levels; and on the other by changes in case-fatality rates, related to medical care. Population centres need to be large and numerous; to reliably establish 10-year trends in event rates within a centre 200 or more fatal events in men per year are needed, while for the collaborative study a multiplicity of internally homogeneous centres showing differing trends will provide the best test of the hypotheses. Forty-one MONICA Collaborating Centres, using a standardized protocol, are studying 118 Reporting Units (subpopulations) with a total population aged 25-64 (both sexes) of about 15 million.
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            Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People With Coronary Disease.

            BACKGROUND: Higher levels of red blood cell distribution width (RDW) may be associated with adverse outcomes in patients with heart failure. We examined the association between RDW and the risk of all-cause mortality and adverse cardiovascular outcomes in a population of people with coronary disease who were free of heart failure at baseline. METHODS AND RESULTS: We performed a post hoc analysis of data from the Cholesterol and Recurrent Events study. Baseline RDW was measured in 4111 participants who were randomized to receive pravastatin 40 mg daily or placebo and followed for a median of 59.7 months. We used Cox proportional hazards models to examine the association between RDW and adverse clinical outcomes. During nearly 60 months of follow-up, 376 participants died. A significant association was noted between baseline RDW level and the adjusted risk of all-cause mortality (hazard ratio per percent increase in RDW, 1.14; 95% confidence interval, 1.05 to 1.24). After categorization based on quartile of baseline RDW and further adjustment for hematocrit and other cardiovascular risk factors, a graded independent relation between RDW and death was observed (P for trend=0.001). For instance, participants with RDW in the highest quartile had an adjusted hazard ratio for death of 1.78 (95% confidence interval, 1.28 to 2.47) compared with those in the lowest quartile. Higher levels of RDW were also associated with increased risk of coronary death/nonfatal myocardial infarction, new symptomatic heart failure, and stroke. CONCLUSIONS: We found a graded independent relation between higher levels of RDW and the risk of death and cardiovascular events in people with prior myocardial infarction but no symptomatic heart failure at baseline.
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              The Malmo Diet and Cancer Study. Design and feasibility.

              The Malmö Diet and Cancer study is a 10-year prospective case-control study in 45-64-year-old men and women (n = 53,000) living in a city with 230,000 inhabitants. One objective is to clarify whether a western diet is associated with certain forms of cancer whilst taking other life-style factors into account. Another broad question is whether oxidative stress and the activity in DNA-repairing systems influence the impact of diet on the development of all or certain forms of cancer. The study is also to act as a resource available for testing new hypotheses emanating from other studies. Initially food intake, heredity, socio-economic factors, life-style pattern, occupational situation, previous and current diseases, symptoms and medications, will be determined. Viable lymphocytes, granulocytes, erythrocytes, and plasma/serum will be stored in a biological bank together with tumour specimens gathered from cases. The incidence and mortality of all cancer forms will then be followed for 10 years by existing registries. Data from the initial examination in these cases will then be compared with those of control subjects not having developed any form of cancer. A biomarker programme, utilizing the biological bank, has been developed and is aimed at finding predictors and/or precursors of cancer. A high participation rate (> 70%) and a high quality biological bank are prerequisites for a successful project. The experience gathered so far indicates that these goals are feasible.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 May 2015
                2015
                : 10
                : 5
                : e0124957
                Affiliations
                [001]Cardiovascular Epidemiology Research Group, Department of Clinical Sciences, Lund University, Malmö, Sweden
                Tufts University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MS YB BH MP GE. Analyzed the data: MS GE. Contributed reagents/materials/analysis tools: MS YB BH MP GE. Wrote the paper: MS YB GE. Revised the manuscript for important intellectual content: BH MP.

                Article
                PONE-D-14-32144
                10.1371/journal.pone.0124957
                4423855
                25950717
                bd447e6e-b6c3-48dc-a412-1902e84054d9
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 17 July 2014
                : 19 March 2015
                Page count
                Figures: 0, Tables: 4, Pages: 14
                Funding
                The authors were supported by grants from the Swedish Heart and Lung Foundation (grant number 20100244; 20130249), the Swedish Stroke Foundation, the Ernhold Lundström Foundation and the Swedish Research Council (grant number 2011–3891). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                The authors do not own the data underlying this study. The data is owned by Lund University, and the research from this database is coordinated by the Malmö Diet and Cancer Study (MDCS) steering committee. A file of raw data underlying this study is available after application to the MDCS steering committee for the purpose of transparency of the present results. No specific requirements are needed. New research projects and publications from MDCS need ethical approval, a full project description, and specific approval from the steering committee. Please email ( Anders.Dahlin@ 123456med.lu.se ) with requests for the data.

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