High heart rate: a cardiovascular risk factor?

Abstract

De battre mon coeur s'est arrêté—Movie by Jacques Audiard. Resting heart rate (RHR) is one of the simplest cardiovascular parameters, which usually averages 60 to 80 beats per minute (b.p.m.), but can occasionally exceed 100 b.p.m. in unconditioned, sedentary individuals and be as low as 30 b.p.m. in highly trained endurance athletes. Epidemiological evidences demonstrate that RHR, or its corollaries, namely post-exercise heart rate recovery, which is mediated primarily by vagal tone, and heart rate variability (HRV, beat-to-beat variability also mediated by autonomic nervous system, especially parasympathetic) correlates with cardiovascular morbidity and suggests that RHR determines life expectancy. Multiple studies have identified RHR as an independent risk factor for cardiovascular disease (comparable with smoking, dyslipidemia or hypertension). However, it is often overlooked. Since 1980, it is known that resting heart rate (RHR) is a prognostic factor in coronary diseased patients.1,2 Data from the Coronary Artery Surgery Study (CASS) published last year underline the prognostic importance of RHR for morbidity (time to rehospitalization), as well as total and cardiovascular mortality.3 Heart rate proves to be the best predictor after myocardial infarction,4,5 in patients with congestive heart failure, as well as in patients with diabetes mellitus or hypertension. In addition, it was found that elevated RHR is also strongly associated with mortality in the general population. For instance, in the Framingham Study, in a cohort composed of 5070 subjects who were free from cardiovascular disease at the time of entry into the study, cardiovascular and coronary mortality increased progressively with RHR6 (Figure 1). In a subset of 4530 untreated hypertensive (>140 mmHg systolic or >90 mmHg diastolic) patients included in this study, using 36-year follow-up data, odds ratio (OR) for each increment in heart rate of 40 b.p.m. were 1.68–1.70 (CI: 1.08–2.67) for cardiovascular mortality and fascinatingly also 2.14–2.18 (CI: 1.59–2.88) for all-cause mortality. This latter study, however, also underlines a key concept: because high RHR is associated with elevated sympathetic activity, it is also frequently related to arterial hypertension. A crucial step is therefore to know whether high RHR is also associated with cardiovascular mortality when controlling for potential confounding cardiovascular risk factors, such as arterial hypertension or age.7 Subsequent analysis demonstrated that rapid RHR was not an indicator of pre-existing illness, but was rather an independent risk factor.8 Moreover, four studies involving hypertensive subjects demonstrated that this effect was sustained in this subset of patients.7–11 This abundant literature was further incremented by data also demonstrating this effect in elderly.12–14 Dependency of heart failure events and sudden cardiac death on RHR divided in quartiles or quintiles. Included are men in a 36-year follow-up in the Framingham Heart Study.6,8 Multiple follow-up studies confirmed these data, as the Cordis trial, the Paris Prospective Study or the MATISS project: Kristal-Boneh et al. (CORDIS)15 found that RHR was strongly associated with both all-cause (RR: 2.23, CI: 1.4–3.6, RHR >90 vs. <70 b.p.m.) and cardiovascular mortality after controlling (in various statistical models) for manifold recognized risk factors. Filipovsky et al. (PPS)16 found that mortality could be predicted by resting heart frequency in 4907 middle-aged males followed during 17 years. Seccareccia et al. (MATISS)17 verified that in a low-risk Italian population, heart rate increment was associated with a relative risk increase from 1.52 (CI: 1.29–1.78) for all-cause mortality, 1.63 (CI: 1.26–2.10) for cardiovascular mortality, and 1.47 (CI:1.19–1.80) for non-cardiovascular mortality. As with cholesterol levels, the risk is graded;9,18 i.e. the risk rises with increasing RHR. In the French IPC trial, Benetos et al.9 evaluated the prognostic value of RHR on mortality in more than 19 000 healthy subjects and found a continuous, graded effect of RHR during a mean follow-up duration of 18.2 years. In men, the relative risk for cardiovascular death was 1.35 (CI: 1.01–1.80) in the group with RHR 60–80 b.p.m. to 2.18 (CI: 1.37–3.47) in the group with RHR >100 b.p.m. Data from the National Health and Nutrition Examination Survey (NHANES I) Epidemiologic follow-up study confirmed this association in white men (RR: 1.37, CI: 1.02–1.84, RHR >84 vs. <74 b.p.m.) and extended this observation to black men and women.19 This is an important finding because it has been considered that high RHR was only a weak predictor in the female gender. The key studies on the topic are listed on the Table 1.13,20–27 Main studies on high RHR as cardiovascular risk factor Main studies on high RHR as cardiovascular risk factor On the basis of this evidence, it has been proposed that, as in animals, life span could be predetermined usi