, Volume 66, Issue 2, pp 133–144 | Cite as

Impact of Increased Heart Rate on Clinical Outcomes in Hypertension

Implications for Antihypertensive Drug Therapy
  • Paolo Palatini
  • Athanase Benetos
  • Stevo Julius
Current Opinion


Thirty-eight studies have been published to date on the association between elevated heart rate and mortality. After adjustment for other risk factors, only two studies for all-cause mortality and four studies for cardiovascular mortality reported an absence of association between heart rate and mortality in male populations. This relationship has been found to be generally weaker among females. Most of these studies investigated samples of general populations. The four studies performed in hypertensive men found a positive association between heart rate and all-cause mortality (hazard ratios ranging from 1.9 to 2.0) or cardiovascular mortality (hazard ratios ranging from 1.3 to 1.7). In spite of this evidence, elevated heart rate remains a neglected cardiovascular risk factor in both genders.

The pathogenetic mechanisms connecting high heart rate, hypertension, atherosclerosis and cardiovascular events have also been explicated in many studies. Elevated heart rate is due to an increased sympathetic and decreased parasympathetic tone. This altered balance of the autonomic nervous system tone could explain the increase in events with the increased heart rate. However, it has also been proved that blood flow changes associated with high heart rate favour both the formation of the atherosclerotic lesion and the occurrence of the cardiovascular event.

Reduction of heart rate in hypertensive patients with increased heart rate could be an additional goal of antihypertensive therapy. Several trials retrospectively showed the beneficial effect of cardiac-slowing drugs, such as β-adrenoceptor antagonists (β-blockers) and non-dihydropyridine calcium channel antagonists, on mortality, notably in patients with coronary heart disease, but no published data are available in patients with hypertension free of coronary heart disease. Other antihypertensive drugs that have been shown to reduce the heart rate are centrally acting drugs and angiotensin II receptor antagonists, but their bradycardic effect is rather weak. The f-channel antagonist ivabradine is a selective heart rate-lowering agent with no effect on blood pressure.

Although it has not been proven in existing trials, it would seem reasonable to recommend antihypertensive agents that decrease the heart rate in hypertensive patients with a heart rate higher than 80–85 beats per minute. Since the fast heart rate per se causes cardiovascular damage, all drugs that lower the heart rate have the potential of further reducing cardiovascular events in patients with elevated heart rate. Unfortunately, lowering of the heart rate is not a clinically recognised goal. Prospective trials investigating whether treatment of high heart rate can prevent cardiovascular events, notably in hypertensive patients, are warranted.


Heart Rate Hypertensive Patient Cardiovascular Mortality Increase Heart Rate Rest Heart Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by the University of Padova, Padova, Italy. The authors have no conflicts of interest that are directly relevant to the contents of this review.


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Authors and Affiliations

  • Paolo Palatini
    • 1
  • Athanase Benetos
    • 2
  • Stevo Julius
    • 3
  1. 1.Department of Clinical and Experimental MedicineUniversity of PadovaPadovaItaly
  2. 2.Unité d’Expertise et de Prévention GériatriqueCHU NancyVandoeuvre lès NancyFrance
  3. 3.Division of HypertensionUniversity of MichiganAnn ArborUSA

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