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

Abstract

Background: A higher resting heart rate is associated with an increased probability of cardiovascular complications and premature death in patients with type 2 diabetes mellitus. The impact of heart rate on the risk of developing microvascular complications, such as diabetic retinopathy and nephropathy, is, however, unknown. The present study tests the hypothesis that a higher resting heart rate is associated with an increased incidence and a greater progression of microvascular complications in patients with type 2 diabetes mellitus.

Methods and results: The relation between baseline resting heart rate and the development of a major microvascular event 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. Major microvascular events were defined as a composite of new or worsening nephropathy or new or worsening retinopathy. Patients with a higher baseline heart rate were at increased risk of a new major microvascular complication during follow-up (adjusted hazard ratio: 1.13 per 10 beats per minute; 95% confidence interval: 1.07-1.20; P<0.001). The excess hazard was evident for both nephropathy (adjusted hazard ratio: 1.16 per 10 beats per minute; 95% confidence interval: 1.08-1.25) and retinopathy (adjusted hazard ratio: 1.11 per 10 beats per minute; 95% confidence interval: 1.02-1.21).

Conclusion: Patients with type 2 diabetes mellitus who have a higher resting heart rate experience a greater incidence of new-onset or progressive nephropathy and retinopathy.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925. http://www.advance-trial.com/static/html/prehome/prehome.asp.

Keywords: diabetes mellitus, type 2; heart rate; microcirculation.

Figure 1.

Prevalence of albuminuria according to fifths of heart rate at baseline.

Figure 2.

Effects of baseline heart rate on major microvascular events in subgroups. Adjusted for age, sex, randomized treatment for blood pressure, randomized treatment for glucose, body mass index, duration of diabetes, glycosylated hemoglobin, prior macrovascular complication of diabetes (see text), estimated glomerular filtration rate, urinary albumin:creatinine ratio, systolic blood pressure, diastolic blood pressure, history of hospitalization for heart failure, regular exercise (see text), current cigarette smoking, total cholesterol, triglycerides, atrial fibrillation, use of calcium channel antagonists, and use of β-blockers. Where relevant, the variable used for subgrouping was excluded from the model. Centers of boxes are placed at the estimates of adjusted hazard ratio (HR) for each subgroup. Areas of the boxes are proportional to the reciprocal of the variance of the estimates. Horizontal lines represent 95% confidence intervals (CI). Vertical broken lines indicate the estimate of overall adjusted hazard ratio. The widths of diamonds represent 95% CI. bpm indicates beats per minute.