Elevated myocardial repolarization lability and reduced arterial baroreflex sensitivity in subjects with high–normal blood pressure

It is well accepted that cardiovascular risk and blood pressure are established in a continuous way [1]. This was emphasized in the recent guidelines on the diagnosis and treatment of hypertension (JNC VII and ESC–ESH, 2003) in which a sub-classification of normotension was introduced. Having a high–normal blood pressure increases the risk of developing a sustained hypertension [2] and may also confer an increased cardiovascular risk compared to optimal blood pressure [3]. However, this point remains a controversial issue [4,5]. In this issue of the journal, Myredal et al. [6] have concentrated on surrogate markers of cardiovascular risk, the QT variability index (QTVI) and the baroreflex sensitivity (BRS) as a function of three blood pressure categories (normal blood pressure, high–normal blood pressure and sustained hypertension). The authors report a progressive increase of QTVI and decrease of BRS with increasing blood pressure levels. Based on these results, and on the above-quoted epidemiological report [3], it is tempting to speculate that these abnormalities contribute to the level of risk, possibly via an increased occurrence of dysrhythmias. There are still some issues that need to be emphasized in relation to this finding. First, the categorization of patients is always a challenging task, especially when it is based on only a few blood pressure measurements. Due to blood pressure variability, subjects may easily be misclassified when blood pressure categories are defined using such narrow ranges. An ambulatory blood pressure measurement would have probably helped to categorize these subjects more accurately. The analysis of all the variables in a continuous way within the entire population is more convincing in this respect. Indeed, QTVI and BRS were found to be significantly correlated with blood pressure, which reinforces the likelihood of the association. In addition, although it was interesting to include an hypertensive group to confirm the link between the studied parameters and blood pressure, the choice of renovascular hypertensives to constitute this group may be unfortunate. This brings two additional confounders apart from blood pressure level per se, namely hormonal changes (especially those concerning the renin–angiotensin system) and the likely higher frequency of drug treatment in these usually severe forms of hypertension. Concerning the former, baroreflex control of sympathetic nervous activity has been shown to differ between essential and secondary hypertension [7]. Notwithstanding these possible pitfalls, it is tempting to relate BRS and QTVI changes to increased cardiovascular risk. Indeed, after a myocardial infarction or in patients with heart failure, a decreased baroreflex sensitivity has prognostic implications beyond classical risk factors [8,9]. Does such evidence exist in hypertension or even in the general population? Unfortunately, the answer is no. We still lack any prospective study that definitely addresses this issue. In post-myocardial infarction patients, La Rovere et al. [10] showed that BRS was an independent predictor of sudden death, and probably also lethal dysrhythmia. This supports the view of Myredal et al. [6] linking sympatho–vagal imbalance with an increased occurrence of events in high–normal blood pressure patients, although this link will obviously be more difficult to confirm in this group than for post-myocardial infarction patients. In particular, in Vasan's study, no information was given on sudden death as a specific outcome [3]. Myredal et al. [6] have mainly discussed their findings in terms of the risk of dysrhythmia entailed by BRS alteration. Another interpretation is that an impaired BRS might have contributed to the high–normal level of blood presssure. This is a classical debate supported by the fact that BRS might be genetically determined [11]. Whatever the direction of the relationship, there are potential implications. One possible application is to help identify those high–normal blood pressure patients who are at the highest risk. However, on an individual basis, this task will probably be compounded by the similarity of BRS values found in the ‘normal category’ and in the ‘high–normal’ one. This is reflected by the important overlap between both groups, making it impossible to disclose a pertinent threshold. In addition to this pessimistic view, it should also be noted that there are several ways to measure baroreflex and that, even when using similar methods, the results are rather variable [12]. There is an urgent need to standardize the procedures if the evaluation of BRS is to be continued as a clinical tool. This is one of the goals of the EUROBAVAR group, which is currently completing its practice guidelines dedicated to the study of baroreflex. The merit of the study by Myredal et al. [6] is to provide additional evidence indicating that BRS is a critical marker in the work-up of the cardiovascular system. The authors showed that even slight elevations of blood pressure can have measurable consequences on BRS and QTVI. If this finding is confirmed, the fact that such subtle differences in terms of blood pressure and risk are associated with detectable BRS differences may provide some hope with respect to the usefulness of this marker in the future. It is likely that, as presented by Myredal et al. [6], the higher the risk, the lower the BRS level. In a previous study, we proposed that this index could represent an integrative marker of risk [13]. The rather surprising fact that, even in a low-risk situation, BRS could be discriminatory is of course especially interesting because other parameters for risk stratification in this very frequent situation are critically needed [14]. There is still much to do to make BRS a standard assessment of risk in hypertension and even in the general population. The study by Myredal et al. [6] comprises one step along this path.