Resting heart rate and all-cause and cardiovascular mortality in the general population: a meta-analysis

Background:

Data on resting heart rate and risk of all-cause and cardiovascular mortality are inconsistent; the magnitude of associations between resting heart rate and risk of all-cause and cardiovascular mortality varies across studies. We performed a meta-analysis of prospective cohort studies to quantitatively evaluate the associations in the general population.

Methods:

We searched PubMed, Embase and MEDLINE from inception to Jan. 1, 2015. We used a random-effects model to combine study-specific relative risks and 95% confidence intervals (CIs). We used restricted cubic spline functions to assess the dose–response relation.

Results:

A total of 46 studies were included in the meta-analysis, involving 1 246 203 patients and 78 349 deaths for all-cause mortality, and 848 320 patients and 25 800 deaths for cardiovascular mortality. The relative risk with 10 beats/min increment of resting heart rate was 1.09 (95% CI 1.07–1.12) for all-cause mortality and 1.08 (95% CI 1.06–1.10) for cardiovascular mortality. Compared with the lowest category, patients with a resting heart rate of 60–80 beats/min had a relative risk of 1.12 (95% CI 1.07–1.17) for all-cause mortality and 1.08 (95% CI 0.99–1.17) for cardiovascular mortality, and those with a resting heart rate of greater than 80 beats/min had a relative risk of 1.45 (95% CI 1.34–1.57) for all-cause mortality and 1.33 (95% CI 1.19–1.47) for cardiovascular mortality. Overall, the results did not differ after adjustment for traditional risk factors for cardiovascular disease. Compared with 45 beats/min, the risk of all-cause mortality increased significantly with increasing resting heart rate in a linear relation, but a significantly increased risk of cardiovascular mortality was observed at 90 beats/min. Substantial heterogeneity and publication bias were detected.

Interpretation:

Higher resting heart rate was independently associated with increased risks of all-cause and cardiovascular mortality. This indicates that resting heart rate is a predictor of all-cause and cardiovascular mortality in the general population.Resting heart rate is a familiar, straightforward and inexpensive-to-measure clinical variable, and it can be modified by a number of factors, such as physical activity, psychologic stress, smoking, intake of omega-3 fatty acids and medications.^1–4 Higher heart rate has been linked to increased risks of cardiovascular disease and premature mortality through a multitude of actions, including its detrimental effects on progression of coronary atherosclerosis, on occurrence of myocardial ischemia and ventricular arrhythmia, on left ventricular function and on circulating levels of inflammatory markers.^5–7 However, measurement of resting heart rate has not been recommended in American and European guidelines on risk assessment of cardiovascular disease.^8,9 The major reasons for this may be that the magnitude of risk with each increment of higher resting heart rate has been inconsistent among studies, and that resting heart rate may not be an independent predictor because higher heart rate coexists with traditional risk factors of cardiovascular disease.^10–13 In addition, data are lacking on the dose–response relation between resting heart rate and all-cause and cardiovascular mortality,^5,9 although a previous review showed a continuous increase in risk with resting heart rate above 60 beats/min.⁵Therefore, we conducted a meta-analysis of prospective cohort studies involving the general population, following the MOOSE checklist,¹⁴ to assess the risk of all-cause and cardiovascular mortality associated with each increment of 10 beats/min; to evaluate the possible dose–response relation by restricted cubic spline functions and by pooling risks of all-cause and cardiovascular mortality for comparable categories of resting heart rate (60–80 beats/min and > 80 beats/min); and to evaluate the effect of traditional risk factors of cardiovascular disease on the association of resting heart rate with risk of all-cause and cardiovascular mortality.