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Heritability of arterial stiffness and central blood pressure: the Holy Grail for detecting patients at high cardiovascular risk?

Laurent, Stéphanea; Parati, Gianfrancob,c

doi: 10.1097/HJH.0b013e328356a250
EDITORIAL COMMENTARIES

aUniversité Paris Descartes , Sorbonne Paris-Cité, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital Georges Pompidou, Paris, France; Institut National de la Santé et de la Recherche Médicale, U970, Paris, France

bDepartment of Cardiology, San Luca Hospital, Istituto Auxologico Italiano

cDepartment of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy

Correspondence to Professor Gianfranco Parati, MD, FESC, San Luca Hospital, Istituto Auxologico Italiano, Piazza Brescia 20, Milan 20159, Italy. Tel: +39 02 6191 12949; fax: +39 02 6191 12956; e-mail: gianfranco.parati@unimib.it

Quantification of arterial stiffness and central blood pressure (BP) is increasingly popular among physicians and researchers, not only because of better standardized measurement procedures and the more frequent availability of dedicated devices, but also because the spectrum of their clinical application is progressively enlarging.

Particularly, evidence is available that arterial stiffness has good predictive value for cardiovascular events, independent of conventional cardiovascular risk factors. Although to a lesser extent, this applies also to estimates of central BP. As acknowledged by recent hypertension guidelines [1], an increase in arterial stiffness is regarded as a direct measure of target organ damage, indicating the occurrence of pathological changes in large artery walls under the action of cardiovascular risk factors. An increase in central BP is both an indirect and extended marker of such damage, as several parameters are known to influence the level of central BP, including arterial stiffness, pressure wave reflections (themselves also influenced by the geometry and vasomotor tone of small arteries), stroke volume, and heart rate.

An important issue still under investigation is whether arterial stiffness and central BP measurements can be regarded as surrogate markers of cardiovascular events [2]. From a clinical perspective, in fact, it would be particularly important to establish whether a reduced arterial stiffness and a lower central BP may translate into a reduction in cardiovascular events. If this were the case, these measurements could be used in clinical practice to detect patients at high cardiovascular risk, to intensify preventive measures, and to guide the appropriate therapeutic strategies at a stage when intervention may still be able to reverse damage.

In this context, the demonstration of a high heritability of arterial stiffness and central BP would be an additional strong argument for their more widespread measurement in the general population in order to detect individuals with abnormally high values. The availability of such a demonstration would support the need of extending their measurement to the nuclear family of patients in whom arterial stiffness and/or central BP are found to be elevated, with a higher probability of finding abnormally high values, and with the resulting practical possibility to implement the necessary preventive and therapeutic interventions. In addition, the demonstration of a higher heritability of arterial stiffness and central BP, as compared with peripheral BP, would provide further support to the hypothesis that arterial stiffness and central BP integrate the long-lasting cumulative effects of all cardiovascular risk factors on the arterial wall, including both more recently described cardiovascular risk factors still under investigation, such as infection–inflammation, oxidative stress, low birth weight, fetal programming and genetics [3], and well identified ones, that is, traditional cardiovascular risk factors.

Although several studies have shown the heritability of arterial stiffness, central BP, and wave reflection, and have identified chromosomal regions and genetic components [4–6], heritability was generally found to be only moderate, and reviews summarizing the available evidence on this topic concluded on a limited influence of genetic factors in the determination of these parameters [7,8].

A major advantage of twin studies including both monozygotic and dizygotic pairs is that they can take into account shared family environment, including the potentially deleterious and confounding effects of salt intake, alcohol use, and lack of physical exercise on the arterial wall properties. Because of this, such studies can give more reliable information on the relative contribution of genes and environment in this regard. Few twin studies, however, have studied the determinants of arterial stiffness, central BP, or augmentation index [9–11], showing a limited heritability of these parameters.

The article by Tarnoki et al. [12] published in the present issue of Journal of Hypertension provides a further important contribution with regard to the heritability of central and peripheral hemodynamic parameters. The authors measured arterial stiffness and central BP in 154 monozygotic and 42 dizygotic twin pairs from Hungary and the United States. They observed that age-adjusted, sex-adjusted, and country-adjusted heritability was 60.0% for central SBP and 46.7% for central pulse pressure (PP), as compared with 30.0% for brachial BP. This study also showed a similar heritability for brachial and aortic augmentation index (46.8 and 48.7%, respectively), and a heritability of 50% for arterial stiffness.

Thus, at first sight, the results of this study appear to confirm previous findings that central BP and arterial stiffness are only moderately inheritable [9–11]. Therefore, in such a perspective, the study by Tarnoki et al. [12] might be seen as being rather disappointing in that it reduces the incentive for measuring arterial stiffness and central BP in nuclear families with the objective of detecting genetic abnormalities susceptible of benefit from extended measures of cardiovascular prevention.

However, these results are stimulating from at least two other points of view. The first one is the fact that there is significant (although moderate) heritability of central BP and arterial stiffness associated with significant (although moderate) genetic covariance among aortic pulse wave velocity (PWV), central PP and SBP, and brachial SBP. This finding should encourage performance of further genetic studies on arterial stiffness and central BP, and further investigation of the structural components of the arterial wall involved in arterial stiffening. An additional benefit of such studies could be the detection of new molecular targets for preventive treatment of accelerated vascular aging.

The second aspect is the demonstration that PWV was significantly correlated with central PP more than with brachial PP. The best bivariate Cholesky decomposition model showed a common genetic background between PWV and central PP. These data suggest that genetic factors may affect small arteries, large arteries, and the aorta to a common extent. This mechanistic aspect has rarely been investigated. Only one study [11], to our knowledge, had a mechanistic approach in this regard, although indirect. In 496 women from the Twins UK adult twin registry, including 112 monozygotic and 135 dizygotic pairs, Cecelja et al. [11] showed that augmentation pressure was correlated with aortic tapering (assessed by the ratio of the diameter of the femoral artery to that of the abdominal aorta) and did not independently correlate with aortic PWV. These results [11] suggest that the rise in central BP, part of which was of genetic origin, was mainly related to the geometrical changes or vasomotor tone of peripheral large arteries, rather than to the stiffening of the aorta that would have favored an early return of backward waves. Thus, the studies by Tarnoki et al. [12] and Cecelja et al. [11] yielded different results, which should stimulate additional investigations to determine whether there might be a common genetic background for aortic stiffness and central BP strong enough to account for a significant relationship.

In spite of above-mentioned stimulating results, the study by Tarnoki et al. [12], however, also has some limitations, which have been acknowledged by the authors. One of them is the use of a novel oscillometric device, the Arteriograph [13], for measuring PWV, rather than a conventional device using the classical foot-to-foot PWV method, for which we have plenty of validation studies performed and evidence of clinical relevance. However, it has to be acknowledged that although the principle of the PWV measurement by the Arteriograph, which estimates PWV from a single-site determination of the suprasystolic waveform, has been questioned by a computer model [14], PWV measurements provided by this device have been validated by an invasive investigation [15]. Moreover, the demonstration, provided in the study by Tarnoki et al. [12], that PWV measured by Arteriograph was significantly correlated with central SBP and PP shows that this newer device measures true arterial properties influencing wave reflection and augmentation pressure. Nevertheless, the Arteriograph method may differ to some extent from the foot-to-foot method used in other twin studies [10], which could explain some discrepancies between findings of different articles published on this issue, as underlined above.

In conclusion, the study by Tarnoki et al. [12] provides a valuable contribution to the ongoing research on the genetic and environmental origin of arterial aging. Results are stimulating not only for the research on genetic aspects but also for better understanding of the pathophysiology of normal and accelerated arterial aging, mainly through the relationships between central BP and the geometry, vasomotor tone, and stiffness of large and small arteries.

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ACKNOWLEDGEMENTS

Conflicts of interest

There are no conflicts of interest.

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