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Arterial stiffening and arterial dilation as heritable traits caused by defective vital rubber?

Arterial stiffening and arterial dilation as heritable traits caused by defective vital rubber? This editorial refers to ‘Arterial stiffening is a heritable trait associated with arterial dilation but not wall thickening: a longitudinal study in the twins UK cohort’†, by M. Cecelja et al., on page 2282. There has been keen interest over the last century in the cause of aortic and large elastic conduit artery degeneration seen from middle age in humans but not apparent in corresponding arteries of laboratory animals at any time of life (but surprisingly a feature of birds; see below). William Osler in Baltimore1 and James Mackenzie in London2 tackled these problems with enthusiasm but without benefits of the cuff sphygmomanometer, which had not yet (∼1900) found its place in clinical medicine. Both concentrated on the elastic media, referred to by Osler as ‘vital rubber’, and which was responsible for the mechanical elastic properties of the aortic and arterial wall. Osler, a clinician and pathologist, separated arteriosclerosis into three different types: ‘nodular’, ‘diffuse’, and ‘senile’, probably corresponding to atherosclerosis, hypertension, and isolated systolic hypertension, respectively.1 Introduction of the cuff sphygmomanometer subsequently assisted in separation of these groups, with ‘diffuse’ arteriosclerosis having elevation in both systolic and diastolic pressure, ‘senile’ having isolated systolic hypertension only, and atherosclerosis occurring with any blood pressure, and characterized by greater involvement of the intima of the aorta and major arteries. The disabilities and early deaths of US Presidents Wilson after the First World War, and Roosevelt after the Second World War focused attention on diffuse arteriosclerosis and on hypertension as the silent killer. Seymour Glagov, a cardiovascular pathologist from Chicago,3–5 described the function of the elastic elements of the aortic and arterial media, and the destruction of elastic and muscular units in hypertensive animals, and in normal subjects with changes in age and blood pressure. He described the ageing change (senile arteriosclerosis) as due to fracture of elastin fibres in the media with disorganization of the normal medial pattern up to the point of ‘medionecrosis’, and diffuse arteriosclerosis as an extreme form of the ageing change, associated with target organ damage and leading to a marked increase in aortic stiffness, but with variable changes in the intima, at least in the aorta. This period, now ∼1950, was associated with introduction of effective antihypertensive drugs and acceptance of the vicious circle of hypertension, where hypertension begets hypertension by a renal mechanism, and of malignant hypertension potentially being curable.6 The next 50 years were to become the greatest for the pharmaceutical companies with respect to development and use of cardiovascular drugs. As the ‘nodular’ and ‘diffuse’ forms of arteriosclerosis began to come under control from effective antihypertensive drugs with minimal side effects, attention shifted to Osler’s ‘vital rubber’ of the aortic media, its disturbed elastic function with advancing years, and the genetic and environmental causes. Osler1 had noted that arteriosclerotic disease tended to run in families, and directed attention to the quality of vital rubber that one had inherited and the environmental factors that contributed to change, including poor diet, inactivity, obesity, and smoking. This matter is taken up in this issue of the journal in a study from an experimental group at Kings College Hospital in London, as a follow-up of an investigation of twins conducted by Dr Marina Cecelja with Phil Chowienczyk.7 The authors sought a marker of arterial function as a cushion, and settled on carotid–femoral pulse wave velocity (PWV), and compared its change with aorta-internal diameter, wall thickness, and carotid intima-media thickness, also measured by ultrasound. As previously discussed in a smaller, distinct twin cohort,8 not only PWV, but also waveform characteristics are strongly heritable. We have demonstrated in a previous analysis of waveforms from the UK Twin study that the pulsatile loading characteristics (as manifest by the augmentation index from arterial pressure waveform analysis) are very heritable (∼37%),9 with relatively little extra contribution from body morphometry or mean arterial pressure. The current study was complemented by newer measures of aortic structure and function using more sophisticated modern techniques including cardiac magnetic resonance (CMR). What emerged from this study is a persuasive argument that properties of the vital rubber, described by Osler, were indeed heritable while environmental factors and bad habits have their major effects through change of the intima and other components of the arterial wall. This work was supported by the studies of Wheat et al. on turkeys.10 Turkeys and other birds usually have high blood pressure and high heart rate. They exhibit early aortic degeneration of the same type as that described by Osler, Glagov, and Cecelja. The problem had come to notice first in turkeys for commercial reasons: because farm-bred turkeys often expired suddenly before harvest, from aortic rupture of underlying dissecting aneurysm. It is now regular practice in farming of turkeys to treat with reserpine to lower blood pressure, and thereby to delay aortic degeneration, dissection, and rupture. The studies of turkeys establish a genetic link with predisposition to aortic degeneration, while prevention of aortic rupture with drugs points to the link between rupture and prevention of degeneration. The studies also introduced the modern medical treatment of patients with aortic dissection in conjunction with surgical repair.11 Figure 1 View largeDownload slide Schematic diagram of the aorta section in a young (left) and old (right) human, with inset (below each) the components of the aortic wall. The wall of the older human is disorganized as a consequence of fraying and fracture of the elastic lamellae (yellow) and loss of muscle attachments (red), together with anincrease in collagen fibres (black) and mucoid material (green), and with foci of ‘medionecrosis’. Drawn by C.M. O’Rourke, after Glagov S. Personal communication, 1994. Figure 1 View largeDownload slide Schematic diagram of the aorta section in a young (left) and old (right) human, with inset (below each) the components of the aortic wall. The wall of the older human is disorganized as a consequence of fraying and fracture of the elastic lamellae (yellow) and loss of muscle attachments (red), together with anincrease in collagen fibres (black) and mucoid material (green), and with foci of ‘medionecrosis’. Drawn by C.M. O’Rourke, after Glagov S. Personal communication, 1994. Cecelja et al. are to be complimented for their work on genetics of aortic degeneration and rupture.7 We look forward to further analysis of the underlying mechanisms. The authors do not report heart rate or pulse pressure. The latter can readily be calculated from their tables. The engineering theory of material fatigue relates fatigue and eventual fracture to the number of cycles of stress, and the magnitude of pulsatile stress.11 We predict that further analysis of these data will show that the increase in aortic PWV with age will be related to the product of heart rate and pulse pressure. Conflict of interest: M.F.O. is a founding director of Aortamate and AtCor Medical, companies formed to aid measurement of central aortic pressure, development of software for pulse wave analyses, and methods to reduce aortic stiffness. The other authors report no conflict of interest. Footnotes The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology. † doi:10.1093/eurheartj/ehy165. References 1 Osler W. The Principles and Practice of Medicine . New York : Appleton ; 1906 . p 847 – 853 . 2 Mackenzie J. The Study of the Pulse: Arterial, Venous and Hepatic, and of the Movements of the Heart . Edinburth : Young J Pentland ; 1902 . 3 Wolinsky H , Glagov S. A lamellar unit of aortic medial structure and function in mammals . Circ Res 1967 ; 20 : 99 – 111 . Google Scholar CrossRef Search ADS PubMed 4 Wolinsky H , Glagov S. Nature of species differences in the medial distribution of aortic vasa vasorum in mammals . Circ Res 1967 ; 20 : 409 – 421 . Google Scholar CrossRef Search ADS PubMed 5 Glagov S , Weisenberg E , Zarins CK , Stankunavicius R , Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries . N Engl J Med 1987 ; 316 : 1371 – 1375 . Google Scholar CrossRef Search ADS PubMed 6 Byrom FB. The Hypertensive Vascular Crisis: An Experimental Study . London : Heinemann ; 1969 . 7 Cecelja M , Jiang B , Kheen L , Hussain T , Vieira MS , Phinikaridou A , Greil G , Spector TD , Chowienczyk P. Arterial stiffening is a heritable trait associated with arterial dilation but not wall thickening: a longitudinal study in the twins UK cohort . Eur Heart J 2018 ; 39 : 2282 – 2288 . 8 Hayward C , Benetos A. Hereditary and environmental influences on arterial function . Clin Exp Pharmacol Physiol 2007 ; 34 : 658 – 664 . Google Scholar CrossRef Search ADS PubMed 9 Snieder H , Hayward CS , Perks U , Kelly RP , Kelly PJ , Spector TD. Heritability of central systolic pressure augmentation: a twin study . Hypertension 2000 ; 35 : 574 – 579 . Google Scholar CrossRef Search ADS PubMed 10 Wheat MW Jr . Acute dissecting aneurysms of the aorta: diagnosis and treatment . Am Heart J 1980 ; 99 : 373 – 387 . Google Scholar CrossRef Search ADS PubMed 11 Nichols WW , O’Rourke MF , Vlachopoulos C. McDonald’s Blood Flow in Arteries . 6th ed . London : Hodder Arnold ; 2011 . Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal Oxford University Press

Arterial stiffening and arterial dilation as heritable traits caused by defective vital rubber?

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Oxford University Press
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
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0195-668X
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Abstract

This editorial refers to ‘Arterial stiffening is a heritable trait associated with arterial dilation but not wall thickening: a longitudinal study in the twins UK cohort’†, by M. Cecelja et al., on page 2282. There has been keen interest over the last century in the cause of aortic and large elastic conduit artery degeneration seen from middle age in humans but not apparent in corresponding arteries of laboratory animals at any time of life (but surprisingly a feature of birds; see below). William Osler in Baltimore1 and James Mackenzie in London2 tackled these problems with enthusiasm but without benefits of the cuff sphygmomanometer, which had not yet (∼1900) found its place in clinical medicine. Both concentrated on the elastic media, referred to by Osler as ‘vital rubber’, and which was responsible for the mechanical elastic properties of the aortic and arterial wall. Osler, a clinician and pathologist, separated arteriosclerosis into three different types: ‘nodular’, ‘diffuse’, and ‘senile’, probably corresponding to atherosclerosis, hypertension, and isolated systolic hypertension, respectively.1 Introduction of the cuff sphygmomanometer subsequently assisted in separation of these groups, with ‘diffuse’ arteriosclerosis having elevation in both systolic and diastolic pressure, ‘senile’ having isolated systolic hypertension only, and atherosclerosis occurring with any blood pressure, and characterized by greater involvement of the intima of the aorta and major arteries. The disabilities and early deaths of US Presidents Wilson after the First World War, and Roosevelt after the Second World War focused attention on diffuse arteriosclerosis and on hypertension as the silent killer. Seymour Glagov, a cardiovascular pathologist from Chicago,3–5 described the function of the elastic elements of the aortic and arterial media, and the destruction of elastic and muscular units in hypertensive animals, and in normal subjects with changes in age and blood pressure. He described the ageing change (senile arteriosclerosis) as due to fracture of elastin fibres in the media with disorganization of the normal medial pattern up to the point of ‘medionecrosis’, and diffuse arteriosclerosis as an extreme form of the ageing change, associated with target organ damage and leading to a marked increase in aortic stiffness, but with variable changes in the intima, at least in the aorta. This period, now ∼1950, was associated with introduction of effective antihypertensive drugs and acceptance of the vicious circle of hypertension, where hypertension begets hypertension by a renal mechanism, and of malignant hypertension potentially being curable.6 The next 50 years were to become the greatest for the pharmaceutical companies with respect to development and use of cardiovascular drugs. As the ‘nodular’ and ‘diffuse’ forms of arteriosclerosis began to come under control from effective antihypertensive drugs with minimal side effects, attention shifted to Osler’s ‘vital rubber’ of the aortic media, its disturbed elastic function with advancing years, and the genetic and environmental causes. Osler1 had noted that arteriosclerotic disease tended to run in families, and directed attention to the quality of vital rubber that one had inherited and the environmental factors that contributed to change, including poor diet, inactivity, obesity, and smoking. This matter is taken up in this issue of the journal in a study from an experimental group at Kings College Hospital in London, as a follow-up of an investigation of twins conducted by Dr Marina Cecelja with Phil Chowienczyk.7 The authors sought a marker of arterial function as a cushion, and settled on carotid–femoral pulse wave velocity (PWV), and compared its change with aorta-internal diameter, wall thickness, and carotid intima-media thickness, also measured by ultrasound. As previously discussed in a smaller, distinct twin cohort,8 not only PWV, but also waveform characteristics are strongly heritable. We have demonstrated in a previous analysis of waveforms from the UK Twin study that the pulsatile loading characteristics (as manifest by the augmentation index from arterial pressure waveform analysis) are very heritable (∼37%),9 with relatively little extra contribution from body morphometry or mean arterial pressure. The current study was complemented by newer measures of aortic structure and function using more sophisticated modern techniques including cardiac magnetic resonance (CMR). What emerged from this study is a persuasive argument that properties of the vital rubber, described by Osler, were indeed heritable while environmental factors and bad habits have their major effects through change of the intima and other components of the arterial wall. This work was supported by the studies of Wheat et al. on turkeys.10 Turkeys and other birds usually have high blood pressure and high heart rate. They exhibit early aortic degeneration of the same type as that described by Osler, Glagov, and Cecelja. The problem had come to notice first in turkeys for commercial reasons: because farm-bred turkeys often expired suddenly before harvest, from aortic rupture of underlying dissecting aneurysm. It is now regular practice in farming of turkeys to treat with reserpine to lower blood pressure, and thereby to delay aortic degeneration, dissection, and rupture. The studies of turkeys establish a genetic link with predisposition to aortic degeneration, while prevention of aortic rupture with drugs points to the link between rupture and prevention of degeneration. The studies also introduced the modern medical treatment of patients with aortic dissection in conjunction with surgical repair.11 Figure 1 View largeDownload slide Schematic diagram of the aorta section in a young (left) and old (right) human, with inset (below each) the components of the aortic wall. The wall of the older human is disorganized as a consequence of fraying and fracture of the elastic lamellae (yellow) and loss of muscle attachments (red), together with anincrease in collagen fibres (black) and mucoid material (green), and with foci of ‘medionecrosis’. Drawn by C.M. O’Rourke, after Glagov S. Personal communication, 1994. Figure 1 View largeDownload slide Schematic diagram of the aorta section in a young (left) and old (right) human, with inset (below each) the components of the aortic wall. The wall of the older human is disorganized as a consequence of fraying and fracture of the elastic lamellae (yellow) and loss of muscle attachments (red), together with anincrease in collagen fibres (black) and mucoid material (green), and with foci of ‘medionecrosis’. Drawn by C.M. O’Rourke, after Glagov S. Personal communication, 1994. Cecelja et al. are to be complimented for their work on genetics of aortic degeneration and rupture.7 We look forward to further analysis of the underlying mechanisms. The authors do not report heart rate or pulse pressure. The latter can readily be calculated from their tables. The engineering theory of material fatigue relates fatigue and eventual fracture to the number of cycles of stress, and the magnitude of pulsatile stress.11 We predict that further analysis of these data will show that the increase in aortic PWV with age will be related to the product of heart rate and pulse pressure. Conflict of interest: M.F.O. is a founding director of Aortamate and AtCor Medical, companies formed to aid measurement of central aortic pressure, development of software for pulse wave analyses, and methods to reduce aortic stiffness. The other authors report no conflict of interest. Footnotes The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology. † doi:10.1093/eurheartj/ehy165. References 1 Osler W. The Principles and Practice of Medicine . New York : Appleton ; 1906 . p 847 – 853 . 2 Mackenzie J. The Study of the Pulse: Arterial, Venous and Hepatic, and of the Movements of the Heart . Edinburth : Young J Pentland ; 1902 . 3 Wolinsky H , Glagov S. A lamellar unit of aortic medial structure and function in mammals . Circ Res 1967 ; 20 : 99 – 111 . Google Scholar CrossRef Search ADS PubMed 4 Wolinsky H , Glagov S. Nature of species differences in the medial distribution of aortic vasa vasorum in mammals . Circ Res 1967 ; 20 : 409 – 421 . Google Scholar CrossRef Search ADS PubMed 5 Glagov S , Weisenberg E , Zarins CK , Stankunavicius R , Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries . N Engl J Med 1987 ; 316 : 1371 – 1375 . Google Scholar CrossRef Search ADS PubMed 6 Byrom FB. The Hypertensive Vascular Crisis: An Experimental Study . London : Heinemann ; 1969 . 7 Cecelja M , Jiang B , Kheen L , Hussain T , Vieira MS , Phinikaridou A , Greil G , Spector TD , Chowienczyk P. Arterial stiffening is a heritable trait associated with arterial dilation but not wall thickening: a longitudinal study in the twins UK cohort . Eur Heart J 2018 ; 39 : 2282 – 2288 . 8 Hayward C , Benetos A. Hereditary and environmental influences on arterial function . Clin Exp Pharmacol Physiol 2007 ; 34 : 658 – 664 . Google Scholar CrossRef Search ADS PubMed 9 Snieder H , Hayward CS , Perks U , Kelly RP , Kelly PJ , Spector TD. Heritability of central systolic pressure augmentation: a twin study . Hypertension 2000 ; 35 : 574 – 579 . Google Scholar CrossRef Search ADS PubMed 10 Wheat MW Jr . Acute dissecting aneurysms of the aorta: diagnosis and treatment . Am Heart J 1980 ; 99 : 373 – 387 . Google Scholar CrossRef Search ADS PubMed 11 Nichols WW , O’Rourke MF , Vlachopoulos C. McDonald’s Blood Flow in Arteries . 6th ed . London : Hodder Arnold ; 2011 . Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

European Heart Journal – Oxford University Press

Published: Apr 24, 2018

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