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Published in: Diabetologia 5/2012

01-05-2012 | Article

Resting heart rate and the risk of death and cardiovascular complications in patients with type 2 diabetes mellitus

Authors: G. S. Hillis, M. Woodward, A. Rodgers, C. K. Chow, Q. Li, S. Zoungas, A. Patel, R. Webster, G. D. Batty, T. Ninomiya, G. Mancia, N. R. Poulter, J. Chalmers

Published in: Diabetologia | Issue 5/2012

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Abstract

Aims/hypothesis

An association between resting heart rate and mortality has been described in the general population and in patients with cardiovascular disease. There are, however, few data exploring this relationship in patients with type 2 diabetes mellitus. The current study addresses this issue.

Methods

The relationship between baseline resting heart rate and all-cause mortality, cardiovascular death and major cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) was examined in 11,140 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Study.

Results

A higher resting heart rate was associated with a significantly increased risk of all-cause mortality (fully adjusted HR 1.15 per 10 bpm [95% CI 1.08, 1.21], p < 0.001), cardiovascular death and major cardiovascular outcomes without adjustment and after adjusting for age and sex and multiple covariates. The increased risk associated with a higher baseline resting heart rate was most obvious in patients with previous macrovascular complications (fully adjusted HR for death 1.79 for upper [mean 91 bpm] vs lowest [mean 58 bpm] fifth of resting heart rate in this subgroup [95% CI 1.28, 2.50], p = 0.001).

Conclusions/interpretation

Among patients with type 2 diabetes, a higher resting heart rate is associated with an increased risk of death and cardiovascular complications. It remains unclear whether a higher heart rate directly mediates the increased risk or is a marker for other factors that determine a poor outcome.
Appendix
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Literature
1.
go back to reference Fox K, Borer JS, Camm AJ et al (2007) Resting heart rate in cardiovascular disease. J Am Coll Cardiol 50:823–830PubMedCrossRef Fox K, Borer JS, Camm AJ et al (2007) Resting heart rate in cardiovascular disease. J Am Coll Cardiol 50:823–830PubMedCrossRef
2.
go back to reference Palatini P (2009) Elevated heart rate in cardiovascular diseases: a target for treatment? Prog Cardiovasc Dis 52:46–60PubMedCrossRef Palatini P (2009) Elevated heart rate in cardiovascular diseases: a target for treatment? Prog Cardiovasc Dis 52:46–60PubMedCrossRef
3.
go back to reference Patel A, MacMahon S, Chalmers J et al (2007) Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 370:829–840PubMedCrossRef Patel A, MacMahon S, Chalmers J et al (2007) Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 370:829–840PubMedCrossRef
4.
go back to reference Patel A, MacMahon S, Chalmers J et al (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572PubMedCrossRef Patel A, MacMahon S, Chalmers J et al (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572PubMedCrossRef
5.
go back to reference ADVANCE study group (2001) Study rationale and design of ADVANCE: action in diabetes and vascular disease—preterax and diamicron MR controlled evaluation. Diabetologia 44:1118–1120CrossRef ADVANCE study group (2001) Study rationale and design of ADVANCE: action in diabetes and vascular disease—preterax and diamicron MR controlled evaluation. Diabetologia 44:1118–1120CrossRef
6.
go back to reference Du X, Ninomiya T, de Galan B et al (2009) Risks of cardiovascular events and effects of routine blood pressure lowering among patients with type 2 diabetes and atrial fibrillation: results of the ADVANCE Study. Eur Heart J 30:1128–1135PubMedCrossRef Du X, Ninomiya T, de Galan B et al (2009) Risks of cardiovascular events and effects of routine blood pressure lowering among patients with type 2 diabetes and atrial fibrillation: results of the ADVANCE Study. Eur Heart J 30:1128–1135PubMedCrossRef
7.
go back to reference Woodward M (2005) Epidemiology: study design and data analysis. Chapman and Hall, Boca Raton Woodward M (2005) Epidemiology: study design and data analysis. Chapman and Hall, Boca Raton
8.
go back to reference Lau B, Cole SR, Gange S (2009) Competing risk regression models for epidemiologic data. Am J Epidemiol 170:244–256PubMedCrossRef Lau B, Cole SR, Gange S (2009) Competing risk regression models for epidemiologic data. Am J Epidemiol 170:244–256PubMedCrossRef
9.
go back to reference Stettler C, Bearth A, Allemann S et al (2007) QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up. Diabetologia 50:186–194PubMedCrossRef Stettler C, Bearth A, Allemann S et al (2007) QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up. Diabetologia 50:186–194PubMedCrossRef
10.
go back to reference Anselmino M, Ohrvik J, Ryden L (2010) Resting heart rate in patients with stable coronary artery disease and diabetes: a report from the Euro Heart Survey on diabetes and the heart. Eur Heart J 31:3040–3045PubMedCrossRef Anselmino M, Ohrvik J, Ryden L (2010) Resting heart rate in patients with stable coronary artery disease and diabetes: a report from the Euro Heart Survey on diabetes and the heart. Eur Heart J 31:3040–3045PubMedCrossRef
11.
go back to reference Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetiere P (2005) Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med 352:1951–1958PubMedCrossRef Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetiere P (2005) Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med 352:1951–1958PubMedCrossRef
12.
go back to reference Diaz A, Bourassa MG, Guertin MC, Tardif JC (2005) Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease. Eur Heart J 26:967–974PubMedCrossRef Diaz A, Bourassa MG, Guertin MC, Tardif JC (2005) Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease. Eur Heart J 26:967–974PubMedCrossRef
13.
go back to reference Linnemann B, Janka HU (2003) Prolonged QTc interval and elevated heart rate identify the type 2 diabetic patient at high risk for cardiovascular death. The Bremen Diabetes Study. Exp Clin Endocrinol Diabetes 111:215–222PubMedCrossRef Linnemann B, Janka HU (2003) Prolonged QTc interval and elevated heart rate identify the type 2 diabetic patient at high risk for cardiovascular death. The Bremen Diabetes Study. Exp Clin Endocrinol Diabetes 111:215–222PubMedCrossRef
14.
go back to reference Cardoso CR, Salles GF, Deccache W (2003) Prognostic value of QT interval parameters in type 2 diabetes mellitus: results of a long-term follow-up prospective study. J Diabetes Complications 17:169–178PubMedCrossRef Cardoso CR, Salles GF, Deccache W (2003) Prognostic value of QT interval parameters in type 2 diabetes mellitus: results of a long-term follow-up prospective study. J Diabetes Complications 17:169–178PubMedCrossRef
15.
go back to reference Poulter NR, Dobson JE, Sever PS, Dahlof B, Wedel H, Campbell NR (2009) Baseline heart rate, antihypertensive treatment, and prevention of cardiovascular outcomes in ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial). J Am Coll Cardiol 54:1154–1161PubMedCrossRef Poulter NR, Dobson JE, Sever PS, Dahlof B, Wedel H, Campbell NR (2009) Baseline heart rate, antihypertensive treatment, and prevention of cardiovascular outcomes in ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial). J Am Coll Cardiol 54:1154–1161PubMedCrossRef
16.
go back to reference Mensink GB, Hoffmeister H (1997) The relationship between resting heart rate and all-cause, cardiovascular and cancer mortality. Eur Heart J 18:1404–1410PubMed Mensink GB, Hoffmeister H (1997) The relationship between resting heart rate and all-cause, cardiovascular and cancer mortality. Eur Heart J 18:1404–1410PubMed
17.
go back to reference Seccareccia F, Pannozzo F, Dima F et al (2001) Heart rate as a predictor of mortality: the MATISS project. Am J Public Health 91:1258–1263PubMedCrossRef Seccareccia F, Pannozzo F, Dima F et al (2001) Heart rate as a predictor of mortality: the MATISS project. Am J Public Health 91:1258–1263PubMedCrossRef
18.
go back to reference Fujiura Y, Adachi H, Tsuruta M, Jacobs DR Jr, Hirai Y, Imaizumi T (2001) Heart rate and mortality in a Japanese general population: an 18-year follow-up study. J Clin Epidemiol 54:495–500PubMedCrossRef Fujiura Y, Adachi H, Tsuruta M, Jacobs DR Jr, Hirai Y, Imaizumi T (2001) Heart rate and mortality in a Japanese general population: an 18-year follow-up study. J Clin Epidemiol 54:495–500PubMedCrossRef
19.
go back to reference Kuzuya M, Enoki H, Iwata M, Hasegawa J, Hirakawa Y (2008) J-shaped relationship between resting pulse rate and all-cause mortality in community-dwelling older people with disabilities. J Am Geriatr Soc 56:367–368PubMedCrossRef Kuzuya M, Enoki H, Iwata M, Hasegawa J, Hirakawa Y (2008) J-shaped relationship between resting pulse rate and all-cause mortality in community-dwelling older people with disabilities. J Am Geriatr Soc 56:367–368PubMedCrossRef
20.
go back to reference Dyer AR, Persky V, Stamler J et al (1980) Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiologic studies. Am J Epidemiol 112:736–749PubMed Dyer AR, Persky V, Stamler J et al (1980) Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiologic studies. Am J Epidemiol 112:736–749PubMed
21.
go back to reference Palatini P, Casiglia E, Julius S, Pessina AC (1999) High heart rate: a risk factor for cardiovascular death in elderly men. Arch Intern Med 159:585–592PubMedCrossRef Palatini P, Casiglia E, Julius S, Pessina AC (1999) High heart rate: a risk factor for cardiovascular death in elderly men. Arch Intern Med 159:585–592PubMedCrossRef
22.
go back to reference Sa Cunha R, Pannier B, Benetos A et al (1997) Association between high heart rate and high arterial rigidity in normotensive and hypertensive subjects. J Hypertens 15:1423–1430PubMedCrossRef Sa Cunha R, Pannier B, Benetos A et al (1997) Association between high heart rate and high arterial rigidity in normotensive and hypertensive subjects. J Hypertens 15:1423–1430PubMedCrossRef
23.
go back to reference Heidland UE, Strauer BE (2001) Left ventricular muscle mass and elevated heart rate are associated with coronary plaque disruption. Circulation 104:1477–1482PubMedCrossRef Heidland UE, Strauer BE (2001) Left ventricular muscle mass and elevated heart rate are associated with coronary plaque disruption. Circulation 104:1477–1482PubMedCrossRef
24.
go back to reference Huikuri HV, Jokinen V, Syvanne M et al (1999) Heart rate variability and progression of coronary atherosclerosis. Arterioscler Thromb Vasc Biol 19:1979–1985PubMedCrossRef Huikuri HV, Jokinen V, Syvanne M et al (1999) Heart rate variability and progression of coronary atherosclerosis. Arterioscler Thromb Vasc Biol 19:1979–1985PubMedCrossRef
25.
go back to reference Spinale FG, Hendrick DA, Crawford FA, Smith AC, Hamada Y, Carabello BA (1990) Chronic supraventricular tachycardia causes ventricular dysfunction and subendocardial injury in swine. Am J Physiol 259:H218–H229PubMed Spinale FG, Hendrick DA, Crawford FA, Smith AC, Hamada Y, Carabello BA (1990) Chronic supraventricular tachycardia causes ventricular dysfunction and subendocardial injury in swine. Am J Physiol 259:H218–H229PubMed
26.
go back to reference Jurca R, Jackson AS, LaMonte MJ et al (2005) Assessing cardiorespiratory fitness without performing exercise testing. Am J Prev Med 29:185–193PubMedCrossRef Jurca R, Jackson AS, LaMonte MJ et al (2005) Assessing cardiorespiratory fitness without performing exercise testing. Am J Prev Med 29:185–193PubMedCrossRef
27.
go back to reference Palatini P, Julius S (1999) The physiological determinants and risk correlations of elevated heart rate. Am J Hypertens 12:3S–8SPubMedCrossRef Palatini P, Julius S (1999) The physiological determinants and risk correlations of elevated heart rate. Am J Hypertens 12:3S–8SPubMedCrossRef
28.
go back to reference Yeap BB, Russo A, Fraser RJ, Wittert GA, Horowitz M (1996) Hyperglycemia affects cardiovascular autonomic nerve function in normal subjects. Diabetes Care 19:880–882PubMedCrossRef Yeap BB, Russo A, Fraser RJ, Wittert GA, Horowitz M (1996) Hyperglycemia affects cardiovascular autonomic nerve function in normal subjects. Diabetes Care 19:880–882PubMedCrossRef
29.
go back to reference Marfella R, Nappo F, de Angelis L, Siniscalchi M, Rossi F, Giugliano D (2000) The effect of acute hyperglycaemia on QTc duration in healthy man. Diabetologia 43:571–575PubMedCrossRef Marfella R, Nappo F, de Angelis L, Siniscalchi M, Rossi F, Giugliano D (2000) The effect of acute hyperglycaemia on QTc duration in healthy man. Diabetologia 43:571–575PubMedCrossRef
30.
go back to reference Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL (1991) Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest 87:2246–2252PubMedCrossRef Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL (1991) Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest 87:2246–2252PubMedCrossRef
31.
go back to reference Vinik AI, Maser RE, Mitchell BD, Freeman R (2003) Diabetic autonomic neuropathy. Diabetes Care 26:1553–1579PubMedCrossRef Vinik AI, Maser RE, Mitchell BD, Freeman R (2003) Diabetic autonomic neuropathy. Diabetes Care 26:1553–1579PubMedCrossRef
32.
go back to reference Ziegler D, Dannehl K, Muhlen H, Spuler M, Gries FA (1992) Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses at various stages of diabetic neuropathy. Diabet Med 9:806–814PubMedCrossRef Ziegler D, Dannehl K, Muhlen H, Spuler M, Gries FA (1992) Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses at various stages of diabetic neuropathy. Diabet Med 9:806–814PubMedCrossRef
33.
go back to reference Ziegler D, Gries FA, Spuler M, Lessmann F (1992) The epidemiology of diabetic neuropathy. Diabetic Cardiovascular Autonomic Neuropathy Multicenter Study Group. J Diabetes Complications 6:49–57PubMedCrossRef Ziegler D, Gries FA, Spuler M, Lessmann F (1992) The epidemiology of diabetic neuropathy. Diabetic Cardiovascular Autonomic Neuropathy Multicenter Study Group. J Diabetes Complications 6:49–57PubMedCrossRef
34.
go back to reference Maser RE, Mitchell BD, Vinik AI, Freeman R (2003) The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care 26:1895–1901PubMedCrossRef Maser RE, Mitchell BD, Vinik AI, Freeman R (2003) The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care 26:1895–1901PubMedCrossRef
35.
go back to reference Ziegler D, Dannehl K, Volksw D, Muhlen H, Spuler M, Gries FA (1992) Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis and standard tests of heart-rate variation in newly diagnosed IDDM patients. Diabetes Care 15:908–911PubMedCrossRef Ziegler D, Dannehl K, Volksw D, Muhlen H, Spuler M, Gries FA (1992) Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis and standard tests of heart-rate variation in newly diagnosed IDDM patients. Diabetes Care 15:908–911PubMedCrossRef
36.
go back to reference Carnethon MR, Jacobs DR Jr, Sidney S, Liu K (2003) Influence of autonomic nervous system dysfunction on the development of type 2 diabetes: the CARDIA Study. Diabetes Care 26:3035–3041PubMedCrossRef Carnethon MR, Jacobs DR Jr, Sidney S, Liu K (2003) Influence of autonomic nervous system dysfunction on the development of type 2 diabetes: the CARDIA Study. Diabetes Care 26:3035–3041PubMedCrossRef
37.
go back to reference Carnethon MR, Golden SH, Folsom AR, Haskell W, Liao D (2003) Prospective investigation of autonomic nervous system function and the development of type 2 diabetes: the Atherosclerosis Risk in Communities Study, 1987–1998. Circulation 107:2190–2195PubMedCrossRef Carnethon MR, Golden SH, Folsom AR, Haskell W, Liao D (2003) Prospective investigation of autonomic nervous system function and the development of type 2 diabetes: the Atherosclerosis Risk in Communities Study, 1987–1998. Circulation 107:2190–2195PubMedCrossRef
38.
go back to reference Kjekshus JK (1986) Importance of heart rate in determining beta-blocker efficacy in acute and long-term acute myocardial infarction intervention trials. Am J Cardiol 57:43F–49FPubMedCrossRef Kjekshus JK (1986) Importance of heart rate in determining beta-blocker efficacy in acute and long-term acute myocardial infarction intervention trials. Am J Cardiol 57:43F–49FPubMedCrossRef
39.
go back to reference Lechat P, Escolano S, Golmard JL et al (1997) Prognostic value of bisoprolol-induced hemodynamic effects in heart failure during the Cardiac Insufficiency BIsoprolol Study (CIBIS). Circulation 96:2197–2205PubMed Lechat P, Escolano S, Golmard JL et al (1997) Prognostic value of bisoprolol-induced hemodynamic effects in heart failure during the Cardiac Insufficiency BIsoprolol Study (CIBIS). Circulation 96:2197–2205PubMed
40.
go back to reference Fox K, Ford I, Steg PG, Tendera M, Ferrari R (2008) Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet 372:807–816PubMedCrossRef Fox K, Ford I, Steg PG, Tendera M, Ferrari R (2008) Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet 372:807–816PubMedCrossRef
41.
go back to reference Swedberg K, Komajda M, Bohm M et al (2010) Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 376:875–885PubMedCrossRef Swedberg K, Komajda M, Bohm M et al (2010) Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 376:875–885PubMedCrossRef
42.
go back to reference Bohm M, Swedberg K, Komajda M et al (2010) Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet 376:886–894PubMedCrossRef Bohm M, Swedberg K, Komajda M et al (2010) Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet 376:886–894PubMedCrossRef
Metadata
Title
Resting heart rate and the risk of death and cardiovascular complications in patients with type 2 diabetes mellitus
Authors
G. S. Hillis
M. Woodward
A. Rodgers
C. K. Chow
Q. Li
S. Zoungas
A. Patel
R. Webster
G. D. Batty
T. Ninomiya
G. Mancia
N. R. Poulter
J. Chalmers
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 5/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2471-y

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