Heart Rate x Blood Pressure = Rate Pressure Product

Kurt Stoschitzky

Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

Correspondence to: Kurt Stoschitzky, Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria, Tel: +43-316-385-80261, Fax: +43-316-385-13733, E-mail: kurt.stoschitzky@medunigraz.at

Abstract

Both heart rate and blood pressure directly correlate with morbidity and mortality, and all antihypertensive drugs decrease blood pressure. However, their effects on heart rate and the Rate Pressure Product (RPP, i.e., the product of heart rate and systolic blood pressure) may show tremendous differences.

This short review tries to explain why the effects of cardiovascular drugs on the RPP may correlate even better with clinical outcome than only their effects on heart rate or blood pressure, and since former large-scale cardiovascular outcome trials did not report their results according to the RPP although they already have them all on file, I would strongly suggest to the authors of these numerous important trials to re-calculate and publish the essential results they already have on file to find out the real context between the RPP on the one hand and morbidity and mortality on the other hand.

Keywords: Rate Pressure Product, Heart rate, Blood pressure, Beta-blockers

In 1945 Franklin D. Roosevelt, the 32nd President of the USA, suffered from hypertension up to >300/190 mmHg: Unfortunately, at this time, hypertension was not considered a disease of major clinical consequence [1], so he was not treated accordingly and died of an intracerebral haemorrhage resulting from malignant hypertension without any effective steps by his physicians to lower his blood pressure [2].

Fortunately, today there is no doubt that high blood pressure markedly increases the risk of morbidity and mortality, and numbers of highly sophisticated national and international Guidelines of arterial hypertension were published and updated regularly all over the world.

However, it took a little bit longer until it was recognized that the relation of heart rate and cardiovascular risk is quite similar to that of blood pressure, and Paolo Palatini and Stevo Julius emphasized in their famous review in 1997 [3]:

• Evidence has been accumulating that heart rate is a major correlate of blood pressure.
• Heart rate may predict the development of sustained hypertension in subjects with normal or borderline elevated blood pressure.
• Heart rate is associated with increased risks of cardiovascular and non-cardiovascular death.
• In spite of this evidence, physicians tend to overlook these facts, and heart rate is either ignored or viewed as a particularly benign prognostic sign.
• It is hard to understand why the importance of heart rate is recognized so poorly in clinical practice and hypertension research.
• Overall, resting clinic heart rate is closely correlated to clinic blood pressure.
• In virtually all studies, heart rate has been found to be correlated significantly to blood pressure.

These perceptions were further supported by the recent original article “Association of the clinic and ambulatory heart rate parameters with mortality in hypertension [4]” which emphasizes that:

• Heart rate parameters derived from ABPM (ambulatory blood pressure monitoring) provide important information, in particular association with death by mean night heart rate, mean 24-h heart rate and reduced day-night heart rate dipping less than 8 beats/minute superior to office heart rate.
• The day-night difference shows an increased risk for cardiovascular death and all-cause death when the drop at night is less than 8 beats/minute.
• Nighttime non-dipping defined as the difference of mean day and mean night heart rate lower than 10%, was associated with an 80% increase in fatal and nonfatal cardiovascular outcomes.
• Morning mean and night peak heart rate were also associated with all-cause, cardiovascular and non-cardiovascular death.
• Heart rate data from ABPM, in particular mean night heart rate, are more closely associated with all-cause, cardiovascular and non-all-cause death than office heart rate. These data show that in addition to the important blood pressure information from ABPM, specific heart rate evaluation might provide important information to identify patients at high risk to die.

Accordingly, I truly appreciate the recent highly sophisticated scientific review “Elevated heart rate and cardiovascular risk in hypertension [5]” where the authors emphasize:

• Overwhelming evidence shows that elevated heart rate is also a marker of greater risk for adverse cardiovascular outcomes and mortality in hypertensive patients.
• Increases in heart rate values are associated with increased norepinephrine outflow from the coronary sinus and greater sympathetic influences on peripheral circulation.
• Heart rate values greater than 80 beats/minute were associated with a marked elevation in sympathetic nerve traffic and thus documented the close relationship between elevated heart rate, sympathetic overdrive, and cardiovascular risk profile.
• Elevated baseline heart rate >80 beats/minute was associated with a 47% higher rate of all-cause mortality.
• Sympathetic cardiovascular influences are known to be increased in hypertension and several cardiovascular diseases and to have an independent adverse effect on patient morbidity and survival.
• Removal of the sympathetic drive has been shown to reduce the stiffness of arteries independently of blood pressure: This indicates that sympathetic vascular drive may exert a direct stiffening influence on the vascular wall.
• The ESC/ESH hypertension guidelines underline the importance of beta-blocking agents and non-dihydropyridine calcium antagonists as antihypertensive drugs of choice in patients with hypertension and atrial fibrillation to control the ventricular response rate.
• Beta-blockers usually trigger heart rate reductions of greater magnitude than central agents.
• Because beta-blockers reduce blood pressure as effectively as other major drug classes and have been shown to reduce cardiovascular morbidity and mortality in placebo-controlled blood pressure-lowering randomized trials, their use in hypertensive patients in whom a higher heart rate makes heart rate reduction desirable is justified.
• Most guidelines regard beta-blockers as preferable in conditions such as angina pectoris, heart failure and the post-myocardial infarction phase, but also when hypertension is associated with increased sympathetic activity and elevated heart rate.
• An advantage of beta-blockers is that they can be combined with all other major drug classes, with the exception of non-dihydropyridine calcium antagonists.
• Chronically elevated heart rate values are associated with greater morbidity and mortality in the general population and in hypertensive patients.
• Combinations that include therapies that reduce heart rate, such as beta-blockers, can offer a rational treatment strategy.

Taken together, I believe that highly sophisticated International Societies/Colleges/Associations of Cardiology such as the ESC, ACC, AHA, etc., particularly their renowned working committees on arrhythmias such as the European Heart Rhythm Association, and International Societies of Hypertension such as ESH, ASH, ISH, etc. should “move closer together” in order to find out and translate into practice what is best for our patients according to both heart rate and blood pressure.

In this context, it might be particularly important to take a special look at the Rate Pressure Product (RPP), i.e., the product of heart rate and systolic blood pressure (also called “Double Product”), since this might represent cardiovascular risk even better than heart rate or blood pressure alone. In this case, further assessment of morbidity and mortality might be feasible quite easily without further clinical investigations but simply by re-evaluation of the vast amount of already existing but still unpublished data of the RPP available in numerous previously published cardiovascular clinical outcome trials.

In summary, I believe that our current knowledge clearly emphasizes that both heart rate and blood pressure represent major risk factors of morbidity and mortality, thus suggesting that we should pay more attention to elevated heart rate (particularly at night) in addition to that of blood pressure as well as to the effects of antihypertensive and antiarrhythmic drugs not only on blood pressure but as well to those on heart rate.

In addition, these findings further suggest to re-evaluate the vast amount of data from the results of numerous cardiovascular clinical outcome trials already being on file in order to find out the true significance of both heart rate and blood pressure and, particularly, the Rate Pressure Product according to cardiovascular as well as general morbidity and mortality, thus in order to prevent much more patients than today from the lethal effects of both high heart rate and high blood pressure!

Furthermore, this perception might throw new light on the treatment of arterial hypertension and further cardiovascular diseases with drugs that usually decrease both heart rate and blood pressure, such as beta-blockers.