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      Low glomerular filtration rate and risk of stroke: meta-analysis

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          Abstract

          Objective To qualitatively and quantitatively investigate the link between a low estimated glomerular filtration rate (eGFR) at baseline and risk of future stroke.

          Design Systematic review and meta-analysis of prospective studies.

          Data sources PubMed (1966-October 2009) and Embase (1947-October 2009).

          Selection criteria Inclusion criteria were studies that prospectively collected data within cohort studies or clinical trials, estimated glomerular filtration rate at baseline using the modification of diet in renal disease or Cockcroft-Gault equations, assessed incident stroke, had a follow-up of at least one year, and reported quantitative estimates of multivariate adjusted relative risk and 95% confidence interval for stroke associated with an eGFR of 60-90 ml/min/1.73 m 2 or <60 ml/min/1.73 m 2.

          Data abstraction Two investigators independently abstracted data from eligible studies. Estimates were combined using a random effects model. Heterogeneity was assessed by P value of χ 2 statistics and I 2. Publication bias was assessed by visual examination of funnel plots.

          Results 21 articles derived from 33 prospective studies: 14 articles assessed eGFR <60 ml/min/1.73 m 2 and seven assessed eGRF at both <60 ml/min/1.73 m 2 and 60-90 ml/min/1.73 m 2 for a total of 284 672 participants (follow-up 3.2-15 years) with 7863 stroke events. Incident stroke risk increased among participants with an eGFR <60 ml/min/1.73 m 2 (relative risk 1.43, 95% confidence interval 1.31 to 1.57; P<0.001) but not among those with an eGFR of 60-90 ml/min/1.73 m 2 (1.07, 0.98 to 1.17; P=0.15). Significant heterogeneity existed between estimates among patients with an eGFR <60 ml/min/1.73 m 2 (P<0.001). In subgroup analyses among participants with an eGFR <60 ml/min/1.73 m 2, heterogeneity was significant in Asians compared with non-Asians (1.96, 1.73 to 2.23 v 1.25, 1.16 to 1.35; P<0.001), and those with an eGFR of 40-60 ml/min/1.73 m 2 v <40 ml/min/1.73 m 2 (1.28, 1.04 to 1.56 v 1.77, 1.32 to 2.38; P<0.01).

          Conclusions A baseline eGFR <60 ml/min/1.73 m 2 was independently related to incident stroke across a variety of participants and study designs. Prompt and appropriate implementation of established strategies for reduction of vascular risk in people with know renal insufficiency may prevent future strokes.

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          Most cited references58

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          Chronic kidney disease: effects on the cardiovascular system.

          Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.
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            Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies.

            Chronic kidney disease (CKD) is a major public health problem. Conflicting evidence exists among community-based studies as to whether CKD is an independent risk factor for adverse cardiovascular outcomes. After subjects with a baseline history of cardiovascular disease were excluded, data from four publicly available, community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were indirectly calibrated across studies. CKD was defined by a GFR between 15 and 60 ml/min per 1.73 m(2). A composite of myocardial infarction, fatal coronary heart disease, stroke, and death was the primary study outcome. Cox proportional hazards models were used to adjust for study, demographic variables, educational status, and other cardiovascular risk factors. The total population included 22,634 subjects; 18.4% of the population was black, and 7.4% had CKD. There were 3262 events. In adjusted analyses, CKD was an independent risk factor for the composite study outcome (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.32), and there was a significant interaction between kidney function and race. Black individuals with CKD had an adjusted HR of 1.76 (95% CI, 1.35-2.31), whereas whites had an adjusted HR of 1.13 (95% CI, 1.02-1.26). CKD is a risk factor for the composite outcome of all-cause mortality and cardiovascular disease in the general population and a more pronounced risk factor in blacks than in whites. It is hypothesized that this effect may be due to more frequent or more severe subclinical vascular disease secondary to hypertension or diabetes in black individuals.
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              Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: a systematic review.

              As more interventions become available for the treatment of coronary heart disease (CHD), policy makers and health practitioners need to understand the benefits of each intervention, to better determine where to focus resources. This is particularly true when a patient with CHD quits smoking. To conduct a systematic review to determine the magnitude of risk reduction achieved by smoking cessation in patients with CHD. Nine electronic databases were searched from start of database to April 2003, supplemented by cross-checking references, contact with experts, and with large international cohort studies (identified by the Prospective Studies Collaboration). Prospective cohort studies of patients who were diagnosed with CHD were included if they reported all-cause mortality and had at least 2 years of follow-up. Smoking status had to be measured after CHD diagnosis to ascertain quitting. Two reviewers independently assessed studies to determine eligibility, quality assessment of studies, and results, and independently carried out data extraction using a prepiloted, standardized form. From the literature search, 665 publications were screened and 20 studies were included. Results showed a 36% reduction in crude relative risk (RR) of mortality for patients with CHD who quit compared with those who continued smoking (RR, 0.64; 95% confidence interval [CI], 0.58-0.71). Results from individual studies did not vary greatly despite many differences in patient characteristics, such as age, sex, type of CHD, and the years in which studies took place. Adjusted risk estimates did not differ substantially from crude estimates. Many studies did not adequately address quality issues, such as control of confounding, and misclassification of smoking status. However, restriction to 6 higher-quality studies had little effect on the estimate (RR, 0.71; 95% CI, 0.65-0.77). Few studies included large numbers of elderly persons, women, ethnic minorities, or patients from developing countries. Quitting smoking is associated with a substantial reduction in risk of all-cause mortality among patients with CHD. This risk reduction appears to be consistent regardless of age, sex, index cardiac event, country, and year of study commencement.
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                Author and article information

                Contributors
                Role: visiting scholar and instructor
                Role: director and professor
                Role: instructor
                Role: director
                Role: epidemiologist
                Role: associate professor
                Journal
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1468-5833
                2010
                2010
                30 September 2010
                : 341
                : c4249
                Affiliations
                [1 ]Stroke Center, 710 Westwood Plaza, University of California, Los Angeles, CA 90095, USA
                [2 ]Department of Neurology, University of California, Los Angeles
                [3 ]Department of Neurology, Chang Gung Memorial Hospital at Chiayi, Chang Gung University College of Medicine, Taiwan
                [4 ]Department of Neurology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine
                [5 ]Ching-Ten Clinic, Taiwan
                [6 ]Department of Epidemiology, School of Public Health, University of California
                Author notes
                Correspondence to: B Ovbiagele Ovibes@ 123456mednet.ucla.edu
                Article
                leem753731
                10.1136/bmj.c4249
                2948650
                20884696
                c65fa5a3-0fd8-463c-b211-fa883296aaf7
                © Lee et al 2010

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                : 25 June 2010
                Categories
                Research
                Urology
                Epidemiologic Studies
                Stroke
                Diet
                Fluid Electrolyte and Acid-Base Disturbances
                Urological Surgery
                Internet

                Medicine
                Medicine

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