Central Blood Pressure - A novel cardiovascular risk marker

Background  

There is a great deal of interest in central blood pressure due to current evidence that :

1. the merging of forward and backward pressure waves can make central blood pressure values different from peripherally (brachial artery) measured ones,
2. the difference may vary between subjects and so can the centrally vs. the peripherally measured pressure effects of antihypertensive drugs. Lastly,
3. because central blood pressure is the blood pressure to which vital organs and atherosclerosis-prone arteries are exposed, central blood pressure is predictive of cardiovascular morbid and fatal events.

Preliminary evidence shows that central blood pressure’s predictive value is maintained after adjustment for peripheral blood pressure.

I – Central Blood pressure :  a presentation.

1 – With home and ambulatory blood pressure, central blood pressure to compensate lackings of clinical blood pressure. 

The 2007 European Guidelines for the diagnosis and treatment of hypertension acknowledge the fact that the determination of sphygmomanometric systolic and diastolic blood pressure values are a crucial step in the diagnosis of hypertension and contribute to defining hypertensive cardiovascular risk (1).

However the guidelines also emphasise that a number of limitations are inherant to clinical blood pressure measuring and that clinical blood pressure may interfere with the diagnosis of high blood pressure and risk assessment (1). This explains why other blood pressure measurements have been developed and implemented, such as home and ambulatory blood pressure, which may provide additional and perhaps more stringent information of clinical, prognostic and therapeutic relevance.

2 – How central blood pressure is measured and how it is an index of aortic stiffness.

Recent technical developments in the field have provided further measurements, i.e. ‘central’ blood pressure, which is the pressure in the aortic vascular district and thus can be regarded as an index of aortic stiffness (2). This ‘new’ blood pressure ‘marker’, originally determined by complex and invasive aortic measurements, can be calculated from an assessment of pulse wave velocity and a calculation of the augmentation index (3).

3 – The importance of pulse wave velocity and the augmentation index.

Both pulse wave velocity and the augmentation index - serving to calculate central blood pressure - are impaired in established hypertensive states. These two parameters hold clinical value for predicting and stratifying cardiovascular risk in selected populations - end-stage renal disease, and patients with coronary artery disease undergoing percutaneous coronary intervention, as you will read below.

There is also evidence that pulse wave velocity and the augmentation index :

1. correlate with certain measures of end-organ damage better than peripheral (brachial) blood pressure, - of which left ventricular mass and carotid intima-media thickness - (4), and
2. may become important targets for antihypertensive drug treatment, - because the impact of therapeutic intervention is not necessarily the same at central and peripheral sites, even when blood pressure appears to be fully normalised (4).

4 - Determinants of central blood pressure : influence of the adrenergic nervous system.

Central blood pressure is determined by a variety of factors (Figure 1), which directly or indirectly modulate pressure within the aorta.

1. A leading factor dertimining central blood pressure is arterial stiffness, which itself varies according to haemodynamic and non- haemodynamic factors.
2. A leading non- haemodynamic factor, involved in arterial stiffness stems from the adrenergic nervous system - given the evidence that several variables involved in arterial stiffness determination are the subject of sympathetic neural influences.
3. Among these variables involved in arterial stiffness that are subject to sympathetic neural influeences is heart rate, whose artificial and sudden increases evoked by atrial pacing have been shown to trigger marked reductions in arterial distensibility, i.e. the specular parameter of arterial stiffness. The sympathetic nervous system also causes tonic inhibitory influences on arterial distensibility.

Pharmacological removal of such influences, elicited for example by brachial plexus anaesthesia, has been shown to increase arterial distensibility and thus reduce arterial stiffness.
Despite these data, however, no conclusive information are available in man on the relationship between central blood pressure values and direct or indirect indices of adrenergic function and on their modifications induced by cardiovascular disease.

II  Predictive power of central blood pressure for cardiovascular fatal and non fatal events.

1 – Shown in end-stage renal disease, in patients with coronary artery disease undergoing percutaneous coronary intervention, and in a general population of American indians.

 
A number of studies carried out in recent years have convincingly shown that central systolic blood pressure, and more so central pulse pressure, holds a prognostic value for cardiovascular fatal and non fatal events.

1. This has been shown in end-stage renal disease, in which the probability of survival has been reported to be inversely related to aortic pressure in one study (5) and to carotid pulse pressure in another (6).
2. Similar data have been collected in patients with coronary artery disease undergoing percutaneous coronary intervention, in which central augmentation index was related to major cardiovascular events and, to a lesser extent, to all cause mortality (7).
3. A further step forward in our understanding of the clinical value of central pressure has been made with the publication of the Strong Heart study, which collected data in a general population of American Indians, in which the occurrence of fatal- and non-fatal cardiovascular events was predicted by central pulse pressure measurement via radial artery tonometry (8).

2 – Greater than traditional risk factors. Relevance of pulse pressure. 

Three considerations related to the above mentioned studies results deserve to be made.

1. First, all these studies followed a prospective design, with an average follow-up ranging from 24 to 56 months.
2. Second, in all the above mentioned investigations the predictive power of the various indices used to estimate central pressure was much greater than traditional cardiovascular risk factors, even when adjusted for confounders.
3. Finally, the already mentioned Strong Heart Study (8), performed in American Indians, is the first demonstration of the predictive power of central pulse pressure in people apparently free from cardiovascular disease. This finding, therefore, further strengthens the value of this variable as potential cardiovascular risk factor.

III – Central blood pressure and antihypertensive treatment.

1 - Central blood pressure may help in determining optimal antihypertensive treatment.

Recent reports by a well known group of investigators provides further evidence of
central blood pressure abnormalities in hypertension, by showing that

1. Abnormalities in the central haemodynamic profile are not only present in established hypertension but also in “high-normal” blood pressure states, i.e values of 130-139 mmHg systolic and 85-89 mmHg diastolic (9).
2. This finding is strengthened by observations on the marked mismatch observed in treated hypertensive patients between brachial and central blood pressure (10).

Taken together, these two series of data allow for an interesting hypothesis to be advanced, namely that important differences in the central haemodynamic profile characterise untreated normotensive subjects and hypertensive patients who achieve the ‘normotensive state’ in response to antihypertensive drug treatment.

The clinical evidence in favor of this hypothesis arises from the results of the Anglo-Scandinavian Cardiac Outcomes Trial Conduit Artery Function Evaluation (ASCOT-CAFE´) study (11), which demonstrates a more favorable cardiovascular outcome in hypertensive patients treated with a combination of drugs (amlodipine plus perindopril) capable of improving both brachial and (calculated) central blood pressure.

2 – Statins benefits, however, not from effect on central blood pressure.

The importance handed to the possible effects of cardiovascular drugs on central blood pressure has been recently further implemented with the data collected in the Conduit Artery Function Evaluation - Lipid – Lowering - Arm (CAFE-LLA) (11), aimed at assessing whether and to what extent the reduced risk of cardiovascular events documented in hypertensive patients under statin treatment could arise from favorable effects of these drugs on central haemodynamics. The results did not support the hypothesis however, as they showed that the favorable effects of statins on cardiovascular risk profile are not mediated by an improvement in central blood pressure.

Fig 1 : Factors determining central blood pressure.

Conclusion:

A number of ongoing studies and clinical trials will allow to address some unsolved questions related to central blood pressure, namely, the predictive value of central blood pressure as compared to predictive value based on traditional blood pressure assessment. These ongoing studies will also include the possibility that the estimation of central haemodynamics will provide a guidance in the choice of antihypertensive drugs. Finally, ongoing studies will also allow to clarify whether and to what extent assessment of central blood pressure in the near future will replace clinic blood pressure measurement.