LETTERS TO THE EDITOR Is Increased Brachial Pulse Pressure a Reliable Predictor of Cardiovascular Risk in Old Hypertensive Subjects With Metabolic Syndrome?

To the Editor: We wish to congratulate Mule et al for their solid methodology and results regarding the evaluation of pulse pressure (PP) in subjects with metabolic syndrome (MS), which beyond any doubt proved that the peripheral PP is significantly increased in untreated hypertensive subjects with MS, especially in the older ones. “As stated by the authors, this fact . may therefore contribute to explain the enhanced cardiovascular risk associated with MS,” as stated by the investigators. We agree that accelerated vascular aging in subjects with MS leads to higher PP, generating a vicious hemodynamic circle, and, thus, it may partly explain the increased cardiovascular risk, which is described in subjects with MS. Although these data are in line with our previous results, we are concerned about the ability of brachial PP to reflect correctly the level of cardiovascular risk (CV) in subjects with MS. In the same issue of the American Journal of Hypertension, we demonstrated that in treated hypertensive subjects, with a similar range of age to the one described in the second and third tertiles of the study of Mule et al, brachial PP is increased, but at the same time central (carotid) PP is decreased, leading to higher PP amplification. It has been previously described that in subjects with end-stage renal disease the attenuation of PP amplification is considered as a significant predictor of CV mortality. In addition, we have shown that in treated hypertensives with MS, PP amplification was related to organ-specific CV risk and that it was modulated mainly by the increase in heart rate and the “blunting” of pressure-wave reflections. Finally, we have shown that arterial stiffening by MS is more pronounced in hypertensive women than men. Taken all these together, we believe that an increased peripheral PP may potentially lead to an overestimation of CV in aged men with increased heart rate due to MS. For these reasons, it would be very enlightening if the investigators could provide data concerning potential differences in heart rate and sex within the second and third tertiles of age. Although heart rate did not differ between those subjects with MS and without MS, in the totality of the population, we speculate that age-dependent differences on heart rate may exist, as MS is a well-described stimulus of the sympathetic nervous system, and thus this may affect central hemodynamics. In our view, estimation of the CV risk from peripheral PP alone, without the knowledge of central PP, as shown in the Conduit Artery Function Evaluation (CAFÉ) study, as well as without the knowledge of arterial stiffness–related parameters (pulse-wave velocity [PWV] and augmentation index), may be misleading in some cases, as, for example, regarding hypertensive subjects with MS. Furthermore, because the ratio of stroke volume to PP constitutes an index of systemic arterial compliance, it could have been implicated in this study to further support or clarify the investigators’ conclusion, “. the elevated levels of clinic and 24-h PP observed in hypertensive patients with MS in our study may reflect increased large arteries stiffness. ” We believe that the delineation of the very complex and interrelated mechanisms between the aforementioned central hemodynamic parameters (Fig. 1) is very crucial, especially in populations characterized by increased adiposity and alterations involving both the inflammatory process and the autonomic nervous system. In these populations the dissociation between carotid-femoral PWV and pressure-wave reflections is now well described. Therefore, although PWV seems to be a consistent predictor of CV risk, integrating most FIG. 1. Aging and gender are two principal determinants of pulse pressure (PP) amplification. Their effect on PP amplification is modulated by the presence of metabolic syndrome due to alterations in three cardinal hemodynamic parameters: accelerated vascular aging (pulse-wave velocity [PWV], especially in women), accelerated heart rate, and “blunting” of pressure-wave reflections (AI). AJH 2007; 20:1024–1027