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Heart rate: a forgotten link in coronary artery disease?

Nature Reviews Cardiology volume 8, pages 369–379 (2011)Cite this article

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Abstract

A considerable body of evidence indicates that elevated resting heart rate is an independent, modifiable risk factor for cardiovascular events and mortality in patients with coronary artery disease. Elevated heart rate can produce adverse effects in several ways. Firstly, myocardial oxygen consumption is increased at high heart rates, but the time available for myocardial perfusion is reduced, increasing the likelihood of myocardial ischemia. Secondly, exposure of the large elastic arteries to cyclical stretch is increased at high heart rates. This effect can increase the rate at which components of the arterial wall deteriorate. Elastin fibers, which have an extremely slow rate of turnover in adult life, might be particularly vulnerable. Thirdly, elevated heart rate can predispose the myocardium to arrhythmias, and favor the development and progression of coronary atherosclerosis, by adversely affecting the balance between systolic and diastolic flow. Comparisons of the effects of the specific heart-rate-lowering drug ivabradine with those of β-blockers could help clarify the pathophysiological effects of elevated heart rate. Effective heart rate control among patients with coronary artery disease is uncommon in clinical practice, representing a missed therapeutic opportunity.

Key Points

  • Elevated resting heart rate is a modifiable risk factor for cardiovascular events and mortality, but rates of heart rate control are low among patients with coronary artery disease

  • At high heart rates, myocardial oxygen requirement is increased whereas the time available for perfusion, which occurs predominantly during diastole, is reduced potentially causing myocardial ischemia

  • Elevated heart rate increases the number of stretch cycles experienced by large elastic arteries, accelerating deterioration of arterial wall components (especially elastin fibers), leading to increased arterial stiffness

  • In the presence of systemic risk factors, such as dyslipidemia and hyperglycemia, atherosclerosis occurs preferentially at sites in the arterial tree exposed to low or reversing fluid shear stress

  • In the coronary arteries, elevated heart rate adversely affects the balance between atherogenic low and reversing shear stress (during systole) and atheroprotective greater, unidirectional shear stress (during diastole)

  • Clinical trials of the specific heart-rate-lowering agent, ivabradine, have shown that 'pure' heart rate reduction can improve outcomes in patients with a heart rate ≥70 bpm

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Figure 1
Figure 2: Effects of heart rate on development of atherosclerosis and vascular oxidative stress.
Figure 3: All-cause mortality according to quintiles of baseline heart rate, shown as hazard ratios relative to the lowest quintile (<63 bpm), in 24,913 patients with proven or suspected coronary artery disease.106
Figure 4

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Authors and Affiliations

  1. Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK

    Kim M. Fox

  2. University Hospital of Ferrara, Corso Giovecca 203, Ferrara, 44121, Italy

    Roberto Ferrari

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  1. Kim M. Fox
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  2. Roberto Ferrari
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Both authors contributed equally to the article in terms of researching data, discussion of content, writing, and reviewing and editing the manuscript before submission and after peer-review and editing.

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Correspondence to Kim M. Fox.

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K. M. Fox and R. Ferrari have acted as consultants for, and received research support and honoraria from, Servier.

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Fox, K., Ferrari, R. Heart rate: a forgotten link in coronary artery disease?. Nat Rev Cardiol 8, 369–379 (2011). https://doi.org/10.1038/nrcardio.2011.58

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