14
views
0
recommends
+1 Recommend
0 collections
    5
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          A growing number of studies linked elevated concentrations of circulating asymmetric (ADMA) and symmetric (SDMA) dimethylarginine to mortality and cardiovascular disease (CVD) events. To summarize the evidence, we conducted a systematic review and quantified associations of ADMA and SDMA with the risks of all-cause mortality and incident CVD in meta-analyses accounting for different populations and methodological approaches of the studies.

          Methods

          Relevant studies were identified in PubMed until February 2015. We used random effect models to obtain summary relative risks (RR) and 95% confidence intervals (95%CIs), comparing top versus bottom tertiles. Dose-response relations were assessed by restricted cubic spline regression models and potential non-linearity was evaluated using a likelihood ratio test. Heterogeneity between subgroups was assessed by meta-regression analysis.

          Results

          For ADMA, 34 studies (total n = 32,428) investigating associations with all-cause mortality (events = 5,035) and 30 studies (total n = 30,624) investigating the association with incident CVD (events = 3,396) were included. The summary RRs (95%CI) for all-cause mortality were 1.52 (1.37–1.68) and for CVD 1.33 (1.22–1.45), comparing high versus low ADMA concentrations. Slight differences were observed across study populations and methodological approaches, with the strongest association of ADMA being reported with all-cause mortality in critically ill patients. For SDMA, 17 studies (total n = 18,163) were included for all-cause mortality (events = 2,903), and 13 studies (total n = 16,807) for CVD (events = 1,534). High vs. low levels of SDMA, were associated with increased risk of all-cause mortality [summary RR (95%CI): 1.31 (1.18–1.46)] and CVD [summary RR (95%CI): 1.36 (1.10–1.68) Strongest associations were observed in general population samples.

          Conclusions

          The dimethylarginines ADMA and SDMA are independent risk markers for all-cause mortality and CVD across different populations and methodological approaches.

          Related collections

          Most cited references87

          • Record: found
          • Abstract: found
          • Article: not found

          Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies.

          A large number of epidemiologic studies have reported on associations between various "inflammatory" factors and coronary heart disease (CHD). To assess the associations of blood levels of fibrinogen, C-reactive protein (CRP), and albumin and leukocyte count with the subsequent risk of CHD. Meta-analyses of any long-term prospective studies of CHD published before 1998 on any of these 4 factors. Studies were identified by MEDLINE searches, scanning of relevant reference lists, hand searching of cardiology, epidemiology, and other relevant journals, and discussions with authors of relevant reports. All relevant studies identified were included. The following information was abstracted from published reports (supplemented, in several cases, by the authors): size and type of cohort, mean age, mean duration of follow-up, assay methods, degree of adjustment for confounders, and relationship of CHD risk to the baseline assay results. For fibrinogen, with 4018 CHD cases in 18 studies, comparison of individuals in the top third with those in the bottom third of the baseline measurements yielded a combined risk ratio of 1.8 (95% confidence interval [CI], 1.6-2.0) associated with a difference in long-term usual mean fibrinogen levels of 2.9 pmol/L (0.1 g/dL) between the top and bottom thirds (10.3 vs 7.4 pmol/L [0.35 vs 0.25 g/dL]). For CRP, with 1053 CHD cases in 7 studies, the combined risk ratio of 1.7 (95% CI, 1.4-2.1) was associated with a difference of 1.4 mg/L (2.4 vs 1.0 mg/L). For albumin, with 3770 CHD cases in 8 studies, the combined risk ratio of 1.5 (95% CI, 1.3-1.7) was associated with a difference of 4 g/L (38 vs 42 g/L, ie, an inverse association). For leukocyte count, with 5337 CHD cases in the 7 largest studies, the combined risk ratio of 1.4 (95% CI, 1.3-1.5) was associated with a difference of 2.8 x 10(9)/L (8.4 vs 5.6 x 10(9)/L). Each of these overall results was highly significant (P<.0001). The published results from these prospective studies are remarkably consistent for each factor, indicating moderate but highly statistically significant associations with CHD. Hence, even though mechanisms that might account for these associations are not clear, further study of the relevance of these factors to the causation of CHD is warranted.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association.

            There is increasing interest in utilizing novel markers of cardiovascular disease risk, and consequently, there is a need to assess the value of their use. This scientific statement reviews current concepts of risk evaluation and proposes standards for the critical appraisal of risk assessment methods. An adequate evaluation of a novel risk marker requires a sound research design, a representative at-risk population, and an adequate number of outcome events. Studies of a novel marker should report the degree to which it adds to the prognostic information provided by standard risk markers. No single statistical measure provides all the information needed to assess a novel marker, so measures of both discrimination and accuracy should be reported. The clinical value of a marker should be assessed by its effect on patient management and outcomes. In general, a novel risk marker should be evaluated in several phases, including initial proof of concept, prospective validation in independent populations, documentation of incremental information when added to standard risk markers, assessment of effects on patient management and outcomes, and ultimately, cost-effectiveness.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose-response meta-analysis of prospective studies.

              Questions remain about the shape of the dose-response relationship between body mass index (BMI) and pancreatic cancer risk, possible confounding by smoking, and differences by gender or geographic location. Whether abdominal obesity increases risk is unclear. We conducted a systematic review and meta-analysis of prospective studies of the association between BMI, abdominal fatness and pancreatic cancer risk and searched PubMed and several other databases up to January 2011. Summary relative risks (RRs) were calculated using a random-effects model. Twenty-three prospective studies of BMI and pancreatic cancer risk with 9504 cases were included. The summary RR for a 5-unit increment was 1.10 [95% confidence interval (CI) 1.07-1.14, I(2) = 19%] and results were similar when stratified by gender and geographic location. There was evidence of a non-linear association, P(non-linearity) = 0.005; however, among nonsmokers, there was increased risk even within the 'normal' BMI range. The summary RR for a 10-cm increase in waist circumference was 1.11 (95% CI 1.05-1.18, I(2) = 0%) and for a 0.1-unit increment in waist-to-hip ratio was 1.19 (95% CI 1.09-1.31, I(2) = 11%). Both general and abdominal fatness increases pancreatic cancer risk. Among nonsmokers, risk increases even among persons within the normal BMI range.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 November 2016
                2016
                : 11
                : 11
                : e0165811
                Affiliations
                [1 ]Institute of Epidemiology, Christian-Albrechts University of Kiel, Kiel, Germany
                [2 ]Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
                The University of Tokyo, JAPAN
                Author notes

                Competing Interests: The author RM was named as a co-inventor on the patent "Method for determination of arginine, methylated arginines and derivatives thereof." EP1666884 A1/B1, US 2006094122, DE602004020360 D1. The patent was owned and later transferred to a third party by his previous employer. The author does not work for the previous or current owner of the patent and receives no royalties or consulting fees from it and does not pursue any activity in relation to the patent.

                • Conceptualization: WL RM.

                • Data curation: SS SRS RM.

                • Formal analysis: SS.

                • Investigation: SS WL RM.

                • Methodology: SS WL RM.

                • Project administration: WL RM.

                • Resources: WL RM.

                • Visualization: SS.

                • Writing – original draft: SS WL RM.

                • Writing – review & editing: SS SRS WL RM.

                Article
                PONE-D-16-21838
                10.1371/journal.pone.0165811
                5094762
                27812151
                1ecb093f-7d7c-4f72-ad97-d746acfde032
                © 2016 Schlesinger et al

                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
                : 31 May 2016
                : 18 October 2016
                Page count
                Figures: 4, Tables: 4, Pages: 26
                Funding
                Funded by: DFG
                Award ID: EXC306/2
                Award Recipient :
                Funded by: DFG
                Award ID: EXC306/2
                Award Recipient :
                This work was supported by a grant from the German Research Foundation (DFG Excellence Cluster Inflammation at Interfaces EXC306/2).
                Categories
                Research Article
                Medicine and Health Sciences
                Cardiovascular Medicine
                Cardiovascular Diseases
                Research and Analysis Methods
                Research Design
                Cohort Studies
                People and Places
                Demography
                Death Rates
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Death Rates
                Research and Analysis Methods
                Chromatographic Techniques
                Liquid Chromatography
                High Performance Liquid Chromatography
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Research and Analysis Methods
                Spectrum Analysis Techniques
                Inductively Coupled Plasma Emission Spectroscopy
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Plasma
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Plasma
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Blood Plasma
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Blood
                Blood Plasma
                Medicine and Health Sciences
                Hematology
                Blood
                Blood Plasma
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article