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

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 = .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.

Figure 1. Baseline resting heart rate (by fifths) and the risk of death from any cause, cardiovascular death and major cardiovascular events

Figure 1a Death from any cause (p<0.001 for trend) Figure 1b Cardiovascular death (p<0.001 for trend) Figure 1c Major cardiovascular events (p=0.002 for trend) Hazard adjusted for age, sex, ADVANCE study blood pressure treatment arm, ADVANCE study glycaemic control arm, body mass index, duration of diabetes, HbA1c, urinary albumin creatinine ratio, estimated glomerular filtration rate, systolic blood pressure, diastolic blood pressure, history of hospitalisation for heart failure, participation in moderate and/or vigorous exercise for >15 minutes at least once weekly, total cholesterol, triacylglycerol level, atrial fibrillation, treatment with calcium channel blockers and treatment with β-blockers.

Figure 2. Baseline resting heart rate and the risk of death from any cause, cardiovascular death and major cardiovascular events stratified by a history of prior macrovascular complications

Macrovascular disease: Myocardial infarction, stroke, hospital admission for a transient ischemic attack, hospital admission for unstable angina, coronary revascularization, peripheral revascularization or amputation secondary to peripheral vascular disease. Hazard adjusted for age, sex, ADVANCE study blood pressure treatment arm, ADVANCE study glycaemic control arm, body mass index, duration of diabetes, HbA1c, urinary albumin creatinine ratio, estimated glomerular filtration rate, systolic blood pressure, diastolic blood pressure, history of hospitalisation for heart failure, participation in moderate and/or vigorous exercise for >15 minutes at least once weekly, total cholesterol, triacylglycerol level, atrial fibrillation, treatment with calcium channel blockers and treatment with β-blockers.

Figure 3. Baseline resting heart rate and the risk of death from any cause stratified by treatment with β-blockers and by atrial fibrillation

Hazard adjusted for age, sex, ADVANCE study blood pressure treatment arm, ADVANCE study glycaemic control arm, body mass index, duration of diabetes, HbA1c, urinary albumin creatinine ratio, estimated glomerular filtration rate, systolic blood pressure, diastolic blood pressure, history of hospitalisation for heart failure, participation in moderate and/or vigorous exercise for >15 minutes at least once weekly, total cholesterol, triacylglycerol level, atrial fibrillation (only in analysis stratified by treatment with β-blockers), treatment with calcium channel blockers and treatment with β-blockers (only in analysis stratified by history of atrial fibrillation).