The Hemoglobin A 1 c Level as a Progressive Risk Factor for Cardiovascular Death , Hospitalization for Heart Failure , or Death in Patients With Chronic Heart Failure

Methods: A total of 2412 participants (907 with prior diabetes) in the Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program with at least 1 HbA1c level were followed up for a median of 34 months. The incidence of the primary outcome (CV death or HF hospitalization), CV death, and total mortality was calculated according to eighths of the usual HbA1c level ranging from 5.8% or less to greater than 8.6%. Adjusted and unadjusted hazard ratios per 1% rise in HbA1c levels were also calculated. Results: A total of 99.6% of eligible participants were followed up until they developed an outcome or the study finished. The risk of the primary composite outcome, CV death, hospitalization for worsening HF, and total mortality rose progressively with higher levels of usual HbA1c (P for trend .001). After age and sex were adjusted for, hazards of these outcomes per 1% higher HbA1c level were 1.25 (95% confidence interval [CI ],1.20-1.31), 1.24 (95% CI, 1.17-1.31), 1.25 (95% CI, 1.19-1.31), and 1.22 (95% CI, 1.16-1.29), respectively. This relationship was evident in patients with and without diabetes and with reduced or preserved ejection fraction and persisted after adjustment for diabetes, other risk factors, and allocation to candesartan.

[1]  Martin J Shipley,et al.  Relation between blood glucose and coronary mortality over 33 years in the Whitehall Study. , 2006, Diabetes care.

[2]  Hans L. Hillege,et al.  Renal Function as a Predictor of Outcome in a Broad Spectrum of Patients With Heart Failure , 2006, Circulation.

[3]  S. Yusuf,et al.  The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. , 1999, Diabetes care.

[4]  Karl Swedberg,et al.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial , 2003, The Lancet.

[5]  A. Sharrett,et al.  Glycaemia (haemoglobin A1c) and incident ischaemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study , 2005, The Lancet Neurology.

[6]  M. Pfeffer,et al.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial , 2003, The Lancet.

[7]  G. Burch.  [Cardiovascular diseases]. , 1956, Revista medica cubana.

[8]  S. Yusuf,et al.  The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis , 2005, Diabetologia.

[9]  N. Wareham,et al.  Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk) , 2001, BMJ : British Medical Journal.

[10]  Michael Brownlee,et al.  The pathobiology of diabetic complications: a unifying mechanism. , 2005, Diabetes.

[11]  Neil R. Powe,et al.  Meta-Analysis: Glycosylated Hemoglobin and Cardiovascular Disease in Diabetes Mellitus , 2004, Annals of Internal Medicine.

[12]  M. Brownlee.  Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[13]  A. Sharrett,et al.  HbA1c and peripheral arterial disease in diabetes: the Atherosclerosis Risk in Communities study. , 2006, Diabetes care.

[14]  J. Rosenstock,et al.  Prevention of cardiovascular outcomes in type 2 diabetes mellitus: trials on the horizon. , 2005, Endocrinology and metabolism clinics of North America.

[15]  R. Holman,et al.  Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study , 2000, BMJ : British Medical Journal.

[16]  M. Woodward,et al.  Blood glucose and risk of cardiovascular disease in the Asia Pacific region. , 2004, Diabetes care.

[17]  N. Day,et al.  Association of Hemoglobin A1c with Cardiovascular Disease and Mortality in Adults: The European Prospective Investigation into Cancer in Norfolk , 2004, Annals of Internal Medicine.

[18]  H. Gerstein.  Glycosylated Hemoglobin: Finally Ready for Prime Time as a Cardiovascular Risk Factor , 2004, Annals of Internal Medicine.

[19]  M. Pfeffer,et al.  Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme , 2003, The Lancet.

[20]  A. Folsom,et al.  Glycemic control and coronary heart disease risk in persons with and without diabetes: the atherosclerosis risk in communities study. , 2005, Archives of internal medicine.

[21]  J. Tuomilehto,et al.  Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases? , 2003, Diabetes care.

[22]  B. Gersh.  Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study , 2007 .

[23]  Insulin Therapy in Type 2 Diabetes Mellitus , 2021 .

[24]  Karl Swedberg,et al.  Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial , 2003, The Lancet.