Augmenting the Assessment of Marfan Syndrome?

Marfan syndrome (MFS) is a connective tissue disorder characterized by typical skeletal, ocular, and cardiovascular features. The latter include aortic root dilatation, with associated life-threatening complications including dissection, necessitating regular follow-up to monitor changes in aortic root size. At present, however, there is no simple, reliable way of predicting aortic disease progression. Applanation tonometry and pulse wave analysis are increasingly used as a noninvasive means of assessing arterial function.1 The characteristics of the vessel wall determine the nature of pressure wave propagation throughout the arterial tree, including the velocity and magnitude of wave reflections. Reflected waves augment arterial pressure, and thus have a major bearing on pulse pressure. The mechanisms leading to aortic dilatation in MFS remain uncertain, but may well involve impairment of the load-bearing capacity of the aortic wall coupled to increased pulsatile stress. This hypothesis appears to be supported by a number of studies showing that arterial stiffness,2 pulse pressure,3 and augmentation index4 are all associated with aortic root size in MFS. In this issue of American Journal of Hypertension, Mortensen et al. demonstrate for the first time that central augmentation index, determined using applanation tonometry, is associated with disease progression in MFS.5 This study is the largest to date in MFS patients using this methodology, and examines an extremely well characterized population. The technology is also clinically relevant, due to its wide availability and ease of use.1 Furthermore, the transfer function employed by the technique to estimate central pressure does not appear to significantly differ in MFS.4 Most importantly, this is the first longitudinal study of its kind, and despite the relatively short follow-up of 22 months, a substantial proportion of patients met the criteria for disease progression. The study raises the exciting possibility that augmentation index may have a role to play in initial risk stratification, and in planning the frequency of follow-up. What might be the mechanism underlying these observations? Increased central aortic pulsatility might be one reason, and indeed the authors noted that central pulse pressure was associated with progression of aortic root size. Augmentation index is a composite measure, and an alternative explanation may be that differences in aortic stiffness (the study observed variations in pulse wave velocity), peripheral vascular impedance mismatch (affecting reflection magnitude), or the nature of ventricular contraction may influence wave reflection. Thus, the increase in augmentation index could be a consequence of the underlying disease, rather than a direct cause of root dilatation. Of course, it may well be a combination of these factors, and further investigation will be required to explore this. Interestingly, β-blockers are employed to slow the progression of disease, despite increasing augmentation index. Perhaps it is simply the hypotensive effect, with a consequent reduction in pulsatile stress and mean distending arterial pressure, that accounts for the benefit of these drugs. It is conceivable that treatments such as angiotensin receptor blockers, which are known to both retard disease progression and lower augmentation index, may be of relatively greater benefit. This question remains unanswered, and further studies are now certainly justified to explore whether augmentation index has additional utility in guiding ongoing therapeutic interventions in MFS patients. The author declared no conflict of interest.