High Heart Rate in Hypertension

What should the clinician do in patients with tachycardia?

Paolo Palatini, Department of Medicine, University of Padova

Resting Heart Rate (RHR) is a strong predictor of metabolic abnormalities, hypertension, and diabetes. In addition, fast RHR is a major risk factor for development of atherosclerosis, cardiovascular disease, and all-cause mortality. In hypertensive patients with high RHR, a combination therapy that ncludes a cardiac slowing drug seems a sensible strategy.

The Resting Heart Rate (RHR) represents a reliable marker of autonomic nervous system tone. High RHR is due to sympatho-adrenergic predominance reflecting increased sympathetic discharge and reduced vagal activity, a condition that is genetically determined. RHR is a strong predictor of future hypertension, obesity, metabolic abnormalities, and diabetes. In addition, high RHR is closely associated with Cardiovascular (CV) events as well as with CV and total mortality. Thus, there is no doubt that in clinical practice RHR can be used as a reliable and inexpensive marker of risk. However, there are still many doubts about how RHR should be assessed, about the correct interpretation of the RHR level, and whether and how high RHR should be reduced in hypertension.

Heart rate as predictor of hypertension and metabolic abnormalities

Fast RHR has been found to be both cross-sectionally and longitudinally associated with elevated Blood Pressure (BP), increased body mass index, high haematocrit, hyperglycemia, and lipid abnormalities. In the patients with borderline BP levels from the HARVEST study, high RHR was a potent predictor of subsequent development of hypertension needing drug therapy and obesity. These associations were confirmed by two recent meta-analyses which showed that there was a linear relationship between elevated RHR and risk of hypertension, metabolic syndrome, and diabetes.

The mechanisms by which tachycardia induced hypertension, atherosclerosis, and CV damage are well understood. These associations may be explained at least partially by the observation both in experimental and human studies that high RHR is associated with large artery stiffness, measured either with PWV or the augmentation index, which gives an estimate of aortic wave reflection. Elevated heart rate by exposing the arteries to increased magnitude and frequency of mechanical load may eventually cause endothelial dysfunction and increase the stiffness of the vascular wall. It is thus possible that the increase in vascular stiffness favours the development of hypertension in normotensive subjects and promotes the occurrence of CV complications in hypertensive patients.

Heart rate as predictor of hard endpoints

A graded association has been found between RHR and CV events or mortality. In a meta-analysis encompassing 1,246, 203 patients, subjects with RHR of greater than 80 bpm had a 45 per cent increase in risk of total mortality and a 33 per cent increase of CV mortality. In a more recent and largermeta analysis by Aune et al. including 87 studies, there was a 7 per cent increase in risk for coronary artery disease, a 9 per cent increase for sudden death, an 18 per cent increase for congestive heart failure, and a 17 per cent increase for total mortality for each 10 bpm increment in RHR. The association between elevated RHR and increased risk of mortality or CV events appeared even stronger in the hypertensive populations as shown by nine cohort studies and six randomised clinical trials. In the Syst-Eur study, elderly people withRHR> 79 bpm had an 89 per cent increase in risk of all-cause mortality and a 60 per cent increase in risk of CV mortality than subjects with lower RHR. In the hypertensive patients at high CV risk from the VALUE study, both baseline and in-trial RHRs were powerful predictors of the composite CV outcome. An interesting aspect of this study is that a substantial reduction  in the risk of adverse outcomes could be obtained with antihypertensive treatment only in the patients with low  RHR. Also temporal changes in RHR recorded during the follow-up proved to be important predictors of death or CV events.

The role of ambulatory heart rate

It should be pointed out that heart rate is not stable throughout the 24 hours and that it can be subject to important changes mainly due to physical activity and to stressful situations. Thus, the association between heart rate and adverse outcomes might be stronger for heart rate measured with ambulatory monitoring in free ranging subjects. This was actually shown by the ABP-International study in 7600 hypertensive patients followed for 5 years. In this study, night-time heart rate emerged as a strong predictor of CV events with a predictive power greater than that of office RHR. Similar results were later obtained by other studies. Of particular relevance are the data obtained in 56 901 patients from the Spanish BP Monitoring Registry. Also in this study the strongest association with all-cause death was observed for night-time heart rate, and for CV death only mean night-time heart rate was predictive of outcome.

In conclusion, studies performed with 24h ambulatory monitoring have shown that ambulatory heart rate is a stronger predictor of CV and total mortality than office heart rate and that among the ambulatory parameters night-time heart rate has the higher prognostic accuracy.

Photoplethysmographic technology has become nearly ubiquitous in smartphones and smartwatches, enabling patients and physicians to obtain beat-to-beat heart rate recording for long periods of time. However, at the present time no data on the clinical usefulness of these techniques are available.

In this review we have provided ample evidence about the clinical importance of RHR as a CV risk factor. Due to this wealth of data, the latest European Guidelines recommend that RHR be always measured when evaluating a hypertensive patient. However, there are some issues still open to question that may hamper the applicability of RHR measurement in clinical practice. In particular, how RHR should be measured, which RHR level should be considered abnormal,  and whether high RHR should be lowered with pharmacological intervention is still unclear.

Measurement of RHR

Many sources of variability including physical and environmental factors, psychic stimuli, body position, methods of measurement etc. may affect the assessment of heart rate in resting conditions. Thus, to minimise the effect of these confounding variables, the measurement of RHR should be strictly standardised (table). Recommendations on how to measure RHR based on the available evidence have been published in a consensus document of the European Society of Hypertension. Before RHR measurement, subjects should relax for at least five minutes. A number of factors which can alter a subject's haemodynamics such as exercise, alcohol, smoking and coffee consumption should be avoided in the hours preceding measurement. The individual should be comfortably seated, with the legs uncrossed. RHR measurement should follow each BP reading. Thirty seconds are sufficient for obtaining a reliable estimate of heart rate because in most people 30 to 40 cardiac cycles can be averaged out during this time. Two measurements are sufficient for a reliable estimate of RHR but more measurements should be achieved when an important decline from the first to the second reading is observed. The sitting position should be preferred because in epidemiologic studies BP has been more frequently measured in that position and RHR can be measured at the end of each BP measurement.

Although electrocardiography is more precise than pulse palpation especially when heart rate is calculated using an in-built software, it should be borne in mind that only a few cardiac cycles are taken into account when heart rate is measured from ECG whereas pulse rate measurement usually lasts 30 seconds. For this reason, electrocardiographic measurement is not recommended for the measurement of resting heart rate even for research and pulse palpation should be preferred.

Practical advice for the clinician

How heart rate should be measured in the office

  • Make sure that exercise, smoking, alcohol and coffee consumption have been avoided in the 2 hours before measurement
  • Allow the patient to relax for at least 5 minutes
  • Keep the room at comfortable temperature
  • Measure blood pressure and RHR with the patient in the sitting position
  • Measure RHR after each blood pressure measurement
  • Measure RHR preferably by pulse palpation over a 30-second period
  • At least two measurements should be taken but more measurements are needed if heart rate declines considerably at second reading

Definition of fast heart rate

  • A RHR of 80 bpm or higher should be considered abnormal
  • In women RHR is usually 2-3 bpm higher than in men
  • Ambulatory heart rate has a greater prognostic capacity than heart rate measured in the office
  • The upper normal values for 24-hour and night-time heart rates are 80 and 73bpm, respectively

How fast heart rate should be managed in hypertension

  • Non pharmacological measures should be implemented.
  • Pharmacological RHR lowering with antihypertensive drugs should be started if RHR is still ≥ 80 bpm.
  • A drug combination including a beta-blocker should be privileged in most patients.

Definition of tachycardia as a CV risk factor

Some doubts still remain about the clinical utility of measuring RHR because a precise cutoff of normality is difficult to establish. Tachycardia is currently defined in textbooks as a heart rate greater than 100 bpm. However, in the vast majority of epidemiologic studies the heart rate value above which a significant increase in risk was observed was well below the 100 bpm threshold. Most studies found a significant increase in risk for a heart rate ≥80-85 bpm and the European guidelines consider the 80 bpm cutoff as the upper normal limit for RHR. Because of the higher heart rate and the weaker relationship of the heart rate-mortality association commonly seen in women, a slightly higher threshold may be adopted in the female gender. Even more difficult is to identify the upper normal limit for ambulatory heart rates. This concern chiefly applies to heart rate recorded during sleep which is much lower than heart rate measured in the office by healthcare personnel. In a recent analysis of the ABP-International database the normalcy limit for nighttime heart rate was identified with a time-dependent ROC curve analysis using the risk of fatal and non fatal combined CV events as the outcome variable. According to this statistical approach, the optimal night-time heart rate cutoff value for prediction of cardiovascular events was around 73 bpm and for 24-hour heart rate was around 80 bpm.

Is fast RHR a target for treatment in hypertension?

According to most epidemiological studies, 25 to 30 per cent of the hypertensive patients have a resting heart rate ≥ 80 bpm. This large segment of the hypertensive population might benefit from a treatment able to decrease not only BP but also RHR. Lifestyle measures should always be implemented in these patients with the purpose of reducing not only BP but also an elevated RHR. Doctors’ advice should be addressed toward discouraging sedentary habits, smoking, and excessive consumption of alcohol and caffeinated beverages.

Although no results of clinical trials specifically designed to investigate the effect of RHR lowering in human beings without CV diseases are available, pharmacological RHR lowering with antihypertensive drugs should be considered in hypertensive subjects with high RHR. The more so if one considers that most clinical guidelines now recommend the use of combination therapies even in the initial treatment of hypertension. Thus, in hypertensive patients with high RHR a drug combination including a RHR lowering drug seems a sensible strategy. Beta-blockers for their marked bradycardic action should be privileged. In the latest European guidelines, beta-blockers have been recommended for several clinical conditions, one of which is hypertension associated with elevated RHR. Beta-blockers have been shown to reduce BP as effectively as other antihypertensive drug classes and to reduce CV and all-cause mortality in placebo-controlled BP-lowering randomised clinical trials. One possible concern is that recent meta-analyses have suggested that at similar attained BP levels, beta-blockers are less effective than other antihypertensive drugs in terms of stroke prevention. This has been attributed mainly to the smaller effect of beta-blockers on aortic BP compared to other drugs, to a deterioration of the metabolic profile and to the increased risk of new onset diabetes. However, the large majority of the clinical trials have been made with the beta-blocker atenolol and it is known that this drug causes many metabolic disturbances. Today, betablockers provided with vasodilatory activity such as carvedilol and nebivolol or with high beta-1 selectivity such as bisoprolol have a more favourable effect on the metabolic variables and on arterial elasticity compared with older beta-blockers.

Conclusion

This review has shown that the evidence about the CV risk associated with RHR is impressive. Due to this wealth of data, the latest European guidelines on the management of hypertension have recommended that RHR be measured together with BP at each visit.According to the same guidelines, in hypertension associated with tachycardia a therapy that not only reduces BP effectively but also decreases the RHR should be selected. Given the high frequency of fast RHR in patients with hypertension, treatment of elevated RHR in this setting might have a major role for reducing CV disease.

Summary

RHR holds important prognostic information in several clinical conditions including hypertension. High RHR is a strong predictor of metabolic abnormalities, hypertension, and diabetes. In addition, fast RHR is a main risk factor for development of atherosclerosis and cardiovascular disease. A linear association has been found between RHR and cardiovascular or all-cause mortality. In hypertensive patients with high RHR a combination therapy including a cardiac slowing drug seems a sensible strategy.

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Author Bio

Paolo Palatini

Paolo Palatini graduated from the University of Padova School of Medicine (Italy) and completed a 5-year Professorship from University of Michigan (USA). He was former Head of Vascular Medicine Unit at the University of Padova and at present is Senior Scholar of Studium Patavinum at the University of Padova.

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