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      Role of B‐Type Natriuretic Peptide and N‐Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus

      , MD, PhD 1 , 2 , , PhD 1 , , MD, PhD 1 , , MD 3 , , MD, PhD 4 , , MD 5 , , MD 6 , , MD, MPH 1 , , MD 7 , , MD, PhD 8 , , MD 9 , , MD 10 , , MD 1 , , MD 11 , , MD , 2

      Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

      John Wiley and Sons Inc.

      acute coronary syndrome, biomarker, brain natriuretic peptide, cardiac outcomes, diabetes mellitus, Evaluation of Lixisenatide in Acute Coronary Syndrome trial, glucagon‐like peptide‐1, natriuretic peptide, N‐terminal prohormone B‐type natriuretic peptide, risk model, Cardiovascular Disease, Epidemiology, Heart Failure, Diabetes, Type 2

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          Natriuretic peptides are recognized as important predictors of cardiovascular events in patients with heart failure, but less is known about their prognostic importance in patients with acute coronary syndrome. We sought to determine whether B‐type natriuretic peptide ( BNP) and N‐terminal prohormone B‐type natriuretic peptide ( NT‐pro BNP) could enhance risk prediction of a broad range of cardiovascular outcomes in patients with acute coronary syndrome and type 2 diabetes mellitus.

          Methods and Results

          Patients with a recent acute coronary syndrome and type 2 diabetes mellitus were prospectively enrolled in the ELIXA trial (n=5525, follow‐up time 26 months). Best risk models were constructed from relevant baseline variables with and without BNP/ NT‐pro BNP. C statistics, Net Reclassification Index, and Integrated Discrimination Index were analyzed to estimate the value of adding BNP or NT‐pro BNP to best risk models. Overall, BNP and NT‐pro BNP were the most important predictors of all outcomes examined, irrespective of history of heart failure or any prior cardiovascular disease. BNP significantly improved C statistics when added to risk models for each outcome examined, the strongest increments being in death (0.77–0.82, P<0.001), cardiovascular death (0.77–0.83, P<0.001), and heart failure (0.84–0.87, P<0.001). BNP or NT‐pro BNP alone predicted death as well as all other variables combined (0.77 versus 0.77).


          In patients with a recent acute coronary syndrome and type 2 diabetes mellitus, BNP and NT‐pro BNP were powerful predictors of cardiovascular outcomes beyond heart failure and death, ie, were also predictive of MI and stroke. Natriuretic peptides added as much predictive information about death as all other conventional variables combined.

          Clinical Trial Registration

          URL: Unique identifier: NCT01147250.

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          Most cited references 33

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          ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.

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            A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease.

            Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested. In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease. Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95% confidence interval [CI], 0.94 to 1.17; P=0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P=0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95% CI, 1.38 to 2.68; P<0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P<0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group. The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits. ( number, NCT00093015.) 2009 Massachusetts Medical Society
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              The UKPDS risk engine: a model for the risk of coronary heart disease in Type II diabetes (UKPDS 56).

              A definitive model for predicting absolute risk of coronary heart disease (CHD) in male and female people with Type II diabetes is not yet available. This paper provides an equation for estimating the risk of new CHD events in people with Type II diabetes, based on data from 4540 U.K. Prospective Diabetes Study male and female patients. Unlike previously published risk equations, the model is diabetes-specific and incorporates glycaemia, systolic blood pressure and lipid levels as risk factors, in addition to age, sex, ethnic group, smoking status and time since diagnosis of diabetes. All variables included in the final model were statistically significant (P<0.001, except smoking for which P=0.0013) in likelihood ratio testing. This model provides the estimates of CHD risk required by current guidelines for the primary prevention of CHD in Type II diabetes.

                Author and article information

                J Am Heart Assoc
                J Am Heart Assoc
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                29 May 2017
                June 2017
                : 6
                : 6 ( doiID: 10.1002/jah3.2017.6.issue-6 )
                [ 1 ] Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA
                [ 2 ] Department of Cardiology Rigshospitalet Copenhagen Denmark
                [ 3 ] Estudios Clínicos Latinoamérica Rosario Argentina
                [ 4 ] University of Bergen Stavanger University Hospital Stavanger Norway
                [ 5 ] Division of Endocrinology & Metabolism McMaster University Hamilton Ontario Canada
                [ 6 ] Sanofi U.S. Bridgewater NJ
                [ 7 ] Research Center of the Italian Association of Hospital Cardiologists Florence Italy
                [ 8 ] British Heart Foundation Cardiovascular Research Centre University of Glasgow United Kingdom
                [ 9 ] Division of Cardiology University of Washington Medical Center Seattle WA
                [ 10 ] Division of Endocrinology Oregon Health and Science University Portland OR
                [ 11 ] Montreal Heart Institute Université de Montréal Montreal Canada
                Author notes
                [* ] Correspondence to: Lars Køber, MD, Department of Cardiology, Heart Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen DK‐2100, Denmark. E‐mail: lars.koeber@
                © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                Page count
                Figures: 1, Tables: 4, Pages: 28, Words: 8867
                Funded by: Sanofi
                Funded by: Danish Council for Independent Research
                Award ID: DFF—4183‐00550
                Original Research
                Original Research
                Custom metadata
                June 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.1 mode:remove_FC converted:27.10.2017


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