Association between resting heart rate and coronary artery disease, stroke, sudden death and noncardiovascular diseases: a meta-analysis

Abstract

Background: Resting heart rate is linked to risk of coronary artery disease, stroke, sudden death and noncardiovascular diseases. We conducted a meta-analysis to assess these associations in general populations and in populations of patients with hypertension or diabetes mellitus.

Methods: We searched PubMed, Embase and MEDLINE from inception to Mar. 5, 2016. We used a random-effects model to combine study-specific relative risks (RRs). We used restricted cubic splines to assess the dose-response relation.

Results: We included 45 nonrandomized prospective cohort studies in the meta-analysis. The multivariable adjusted RR with an increment of 10 beats/min in resting heart rate was 1.12 (95% confidence interval [CI] 1.09-1.14) for coronary artery disease, 1.05 (95% CI 1.01-1.08) for stroke, 1.12 (95% CI 1.02-1.24) for sudden death, 1.16 (95% CI 1.12-1.21) for noncardiovascular diseases, 1.09 (95% CI 1.06-1.12) for all types of cancer and 1.25 (95% CI 1.17-1.34) for noncardiovascular diseases excluding cancer. All of these relations were linear. In an analysis by category of resting heart rate (< 60 [reference], 60-70, 70-80 and > 80 beats/min), the RRs were 0.99 (95% CI 0.93-1.04), 1.08 (95% CI 1.01-1.16) and 1.30 (95% CI 1.19-1.43), respectively, for coronary artery disease; 1.08 (95% CI 0.98-1.19), 1.11 (95% CI 0.98-1.25) and 1.08 (95% CI 0.93-1.25), respectively, for stroke; and 1.17 (95% CI 0.94-1.46), 1.31 (95% CI 1.12-1.54) and 1.57 (95% CI 1.39-1.77), respectively, for noncardiovascular diseases. After excluding studies involving patients with hypertension or diabetes, we obtained similar results for coronary artery disease, stroke and noncardiovascular diseases, but found no association with sudden death.

Interpretation: Resting heart rate was an independent predictor of coronary artery disease, stroke, sudden death and noncardiovascular diseases over all of the studies combined. When the analysis included only studies concerning general populations, resting heart rate was not associated with sudden death.

Figure 1:

Forest plot of each increment in resting heart rate of 10 beats/min in relation to risk of coronary artery disease. The size of each grey circle is proportional to the weight assigned to that study. Covariable-adjusted risk estimates were used because the raw numbers were not provided in the original studies. Note: CI = confidence interval, M = men, RR = relative risk, W = women.

Figure 2:

Forest plot of each increment in resting heart rate of 10 beats/min in relation to risk of noncardiovascular diseases. The size of each grey circle is proportional to the weight assigned to that study. Covariable-adjusted risk estimates were used because the raw numbers were not provided in the original studies. Note: CI = confidence interval, M = men, RR = relative risk, W = women.

Figure 3:

Dose–response analysis of resting heart rate with risk of (A) coronary artery disease and (B) noncardiovascular diseases. The solid line and the long-dash lines represent the estimated relative risk (RR) and its 95% confidence interval (CI), respectively. The short-dash line represents the linear relation.