This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Avolio, A. Search for Related Content PubMed PubMed Citation Articles by Avolio, A.

(Hypertension. 1995;26:34-37.)
© 1995 American Heart Association, Inc.

Articles

Genetic and Environmental Factors in the Function and Structure of the Arterial Wall

Alberto Avolio

From the Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.

Correspondence to Dr A. Avolio, Graduate School of Biomedical Engineering, University of New South Wales, Sydney 2052, Australia. E-mail a.avolio@unsw.edu.au.

	Abstract

Top Abstract Introduction Pulsatile Arterial Function and... Discussion References

 
Abstract In large arteries the structure of the arterial wall determines pulsatile hemodynamics of pressure and flow. Mechanical wall stiffness, wall thickness, and elastin and collagen content vary along the arterial tree. The contribution of genetic and environmental factors to such structural properties is not yet known, but some data are available on possible functional correlates. In hypertensive rats diastolic and pulse pressure have been shown to be linked to two different genes on separate chromosomes. Although a genetic component contributes to intimal calcification, medial hypertrophy is not associated with genetic factors. A study of French West Indies families showed a preferential genetic determinant for pulse pressure in contrast to systolic or diastolic pressure. Environmental and geographic factors are associated with markedly different prevalences of hypertension and age-related increases in arterial stiffening in urban and rural communities in China. Salt consumption has also been implicated in modifications of pulse wave velocity. Recent data on structural parameters of the aortic trunk in oriental (Chinese) and occidental (American and Australian) subjects have shown that the ascending aorta in oriental subjects is of a relatively larger diameter and thinner media. This suggests that in this population a relatively higher primary pressure pulse would be generated because of increased stiffness of the proximal aorta. This suggests that factors other than arterial pressure are responsible for structural differences in the aortic wall and that oriental populations may have a predisposition to increased arterial pressure based on structural factors that affect the interaction between ventricular ejection and arterial load.

Key Words: population • aorta • atherosclerosis • blood pressure • sodium, dietary

	Introduction

Top Abstract Introduction Pulsatile Arterial Function and... Discussion References

 
Studies of genetic and environmental determinants of many cardiovascular disorders abound, especially with the recent advances in the science of molecular biology. Hypertension has traditionally been at the forefront of the controversy of whether its causes are predominantly genetic, whether an increase in arterial pressure is an inherent outcome of the aging process, and whether there is significant modification of arterial pressure by external environment such as dietary salt and lifestyle patterns.^{1 2 3} Such issues are addressed by epidemiological studies in human populations^{4 5} or laboratory studies in animal models of hypertension, mainly in spontaneously hypertensive rats (SHR).^{6 7} Although arterial pressure is a pulsatile phenomenon, the approach has been to consider aspects of the circulation that relate to steady or nonoscillatory factors such as fluid volume, peripheral resistance, or cardiac output to gain insight into the determinants of hypertension.⁸ With respect to structural arterial modification, high arterial pressure is known to be associated with altered vascular changes, mainly increases in the wall thickness of resistance vessels.⁹ The question still remains, however, as to whether the trigger is a functional alteration, causing increased intravascular pressure and so producing adaptive structural vascular changes, or whether the arterial vasculature itself is predisposed to vascular changes that precipitate and result in altered arterial pressure. What is common to both points of view is that arterial pressure is developed in the aorta because of the oscillatory nature of ventricular ejection. That is, both the pulsatile function of the heart and arterial system and the structure of the large arteries become relevant factors in gaining an insight into the mechanisms responsible for development of high arterial pressure. The modification of the structure and function of large arteries by genetic and environmental factors thus becomes an issue of importance equal to that of peripheral resistance vessels in understanding underlying mechanisms of arterial disorders and hypertension.

These issues will be addressed against a background of the limited information available on both epidemiological and laboratory evidence of the effects of genetic and environmental factors, specifically on the structure and function of large arteries. With increasing awareness of the importance of pulsatile function of large arteries with respect to the heart (in relation to ventricular hypertrophy) and blood vessels (in relation to arterial pressure) and its modification by new classes of pharmacological agents (such as calcium antagonists and angiotensin-converting enzyme inhibitors), some recent studies have attempted to produce evidence of genetic and environmental associations with pulsatile parameters such as pulse pressure, arterial compliance, and arterial pulse wave velocity.

	Pulsatile Arterial Function and Wall Structure

Top Abstract Introduction Pulsatile Arterial Function and... Discussion References

 
Genetic Factors
Studies relating genetic factors specifically to pulsatile hemodynamic parameters are scarce. A recent study on genetic determinants of arterial pressure in hypertensive rats addressed the problem of genetic heterogeneity by considering different hemodynamic variables as subphenotypes of blood pressure.¹⁰ In the Lyon hypertensive rat strain, the study reports two independent loci for diastolic and pulse pressures. A statistical linkage was found between a marker of the renin gene on chromosome 13 and diastolic pressure and between the carboxypeptidase B gene on chromosome 2 and pulse pressure. Both of these genes also show a statistical linkage to systolic pressure. The authors conclude that the two different genes related to the steady and pulsatile components of blood pressure may therefore be related to corresponding properties of the arterial vasculature and structure of the arterial wall. These are interesting speculations, but it is not yet known whether similar linkages are found with structural components of the arterial wall such as elastin, collagen, and smooth muscle in large arteries and resistance vessels.

Some studies aimed at associating genetic factors with specific events in wall morphology have highlighted the difference between medial and intimal structure. In jejunal arteries cross-transplanted between normotensive Wistar-Kyoto rats (WKY) and SHR, it was shown that medial hypertrophy only occurred in the SHR hosts, that is, independent of genetic factors.¹¹ In contrast, calcification of aortic atheromatous lesions was found to be genetically determined in inbred mouse strains.¹²

Morphological studies in hypertensive and normotensive rats have shown that the arterial wall structure may be specifically modified by long-term treatment with angiotensin-converting inhibitors, leading to functional increase in arterial compliance.^{13 14} It has also been shown that angiotensin II has a pressure-independent effect on smooth muscle hypertrophy¹⁵ and is a major stimulant for collagen synthesis in vitro.¹⁶

An epidemiological study to demonstrate a genetic association with pulse pressure in preference to either systolic or diastolic pressure was performed in a group of 151 nuclear families that constituted 80% of the total population of the French West Indies island of La Désirade.¹⁷ The results of this study, however, do not agree with those of other studies involving twins or relatives of hypertensive subjects who show some degree of genetic linkage with systolic pressure even among normotensive subjects.¹⁸ Without further supporting evidence, it is difficult to interpret these results in relation to structural aspects of large arteries. Furthermore, conclusions drawn on pulse pressure alone do not necessarily pertain to pulsatile arterial function alone but pertain also to a combined effect of pulsatile arterial hemodynamic and ventricular ejection.¹⁹

Several investigators measured structural and functional parameters of the aorta and large arteries in families with hereditary connective tissue disorders. Although alteration of arterial wall structure in certain monogenic syndromes such as Ehlers-Danlos or Marfan's is different from that which occurs with age or hypertension, changes in functional arterial parameters relate to changes in basic properties of load-bearing components. Pulse wave velocity in the upper limb and aortic trunk and lower limb is markedly reduced in families with ecchymotic Ehlers-Danlos syndrome, a condition associated with a collagen type III deficiency.²⁰ Although this genetic factor is involved in improved arterial distensibility, it is at the expense of a serious structural disorder of the arterial wall, which predisposes it to rupture because of the generally weakened structural collagenous support. Specific aortic structural changes have also been described for other connective tissue disorders. Aortic root dilatation and increased wall stiffness occur in the hereditary conditions of osteogenesis imperfecta and Marfan's syndrome.^{21 22} These conditions are associated with an increased frequency of hypertension.²³

Environmental Factors: Population Studies, Pulse Wave Velocity, Arterial Pressure, and Dietary Salt
The contribution of environmental factors to the structure and function of large arteries has been extensively studied in the attempt to uncover the mechanisms responsible for the development of hypertension. Whereas many early studies confirmed the age-related increase in arterial pressure²⁴ and increased arterial stiffness of the aortic wall, others showed that these phenomena are present in different degrees in different populations. In highland populations of New Guinea, the aortic caliber increased with age in males and females to the same degree, whereas pulse pressure decreased in males and increased in females.⁵ Overall, this population did not exhibit the age-related increase in arterial pressure seen in other Western populations. Urban and rural Chinese communities exhibit markedly different increases in arterial pressure and pulse wave velocity with age.^{25 26} The same value of aortic pulse wave velocity in a Southern Guangzhou rural community occurred 30 years of age later compared with that of a Northern Beijing urban community. This difference in increase in pulse wave velocity with age was similar to the prevalence of hypertension in the two communities. The main factor that was implicated to explain the large difference between the two communities was the consumption of dietary salt (7.3 g/d in Guangzhou; 13.3 g/d in Beijing).

While the association between salt consumption and arterial pressure has been subjected to exhaustive investigation, the specific association of salt with properties of the arterial wall has been studied to a lesser degree. Cross-sectional studies of pulse wave velocity in salt-free subjects indicate that wall stiffness is significantly reduced compared with that in age-matched control subjects.²⁷ Decreased arterial compliance has also been found in the carotid, brachial, and femoral arteries of salt-sensitive subjects with borderline hypertension.²⁸ In terms of genetic influences in different racial groups, salt sensitivity is higher in black populations compared with white populations, and this is associated with a higher prevalence of hypertension in blacks.^{29 30} Saline infusion also has been shown to reduce regional brachial artery compliance.³¹ This suggests possible modifications of viscoelastic properties of large arteries in this group of subjects, although confirmation of this would require specific measurements of mechanical properties together with morphological quantification of structural changes. Environmental factors such as aerobic exercise also have been demonstrated to improve arterial pulse wave velocity and wall stiffness³² and total systemic compliance.³³

Aortic Structure
The geometric structure of the aorta in oriental and occidental populations has been examined in a recent study involving postmortem perfusion-fixed aortic specimens of American, Chinese, and Australian subjects.^{34 35} The American and Australian subjects were combined to form the occidental group and were compared with the Chinese (oriental) group. Population data and causes of death are given in Table 1. Compared with the occidental population, the Chinese population was slightly older, had a lower average body weight, and was of a smaller stature. Mortality was lower for cardiovascular causes but much greater for cancer-related causes.

View this table: [in this window] [in a new window]   Table 1. Population Data

Outer circumference, medial thickness, intimal thickness, and degree of intimal atheroma were measured at four separate locations along the aortic trunk (ascending aorta, upper descending thoracic aorta at the level of T6, suprarenal abdominal aorta, and lower abdominal aorta) in subjects ranging from 18 to 103 years of age (n=521). The effects of shrinkage due to tissue processing were previously determined.³⁵ Fixation caused an average retraction in length of 5.8% and in circumference of 6.5%. Embedding caused an average reduction of circumference of 18.9%. Since all specimens were processed in a similar manner, it was deemed unnecessary to correct for these effects when comparing similar age groups.

Comparison of the oriental with the occidental population showed a substantial difference in age-related change of aortic morphology along the aortic trunk. The Chinese showed a relatively lower average intimal thickness throughout the aorta, with a significant difference in the abdominal aorta (Table 2, top). This correlated with a lower atherosclerosis score in this location (Table 2, bottom) and is consistent with the usually accepted fact that oriental populations have a lower prevalence of atherosclerosis than occidental populations.³⁵

View this table: [in this window] [in a new window]   Table 2. Arterial Parameters

The most striking result from this study was the marked difference in the ratio of radius to medial thickness (R/h). Since the aortas were all fixed at the same pressure (100 mm Hg), R/h is proportional to wall stress (S) from Laplace's law: S=P · (R/h). When corrected for the effects of age, height, and weight, the ratio R/h was significantly higher in the Chinese ascending aorta (16%; P<.001), with little variation along the aortic trunk (Figure). Although the Chinese population was of relatively smaller body size, the ascending aorta was larger and the wall thinner. Thus, it is subjected to a relatively higher wall stress. One outcome of this is that the structure of the wall undergoes adaptive changes by increasing the stiffness to compensate for the higher stress. That is, the left ventricle of an oriental subject ejects into a relatively stiffer ascending aorta; thus a similar stroke volume would generate a higher primary pulse pressure. Since the profile of wall stress along the aortic trunk is different, relative stiffness would also be different, thereby affecting the secondary phenomenon of pressure augmentation due to wave reflection. Hence, simply on structural parameters alone, the aortas of oriental subjects would generate a higher pulse pressure compared with the aortas of occidental subjects. On this basis alone, one would conclude that oriental populations are subjected to a higher probability of developing hypertension.

View larger version (15K): [in this window] [in a new window]   Figure 1. Line graph shows values of ratio of aortic radius to medial thickness (R/h) for ascending aorta (A), descending aorta (B), suprarenal abdominal aorta (C), and lower abdominal aorta (D) for oriental (Chinese) and occidental (Australian [AUS] and American [US]) subjects. Values (mean, SEM) are plotted as a function of average distance along the aortic trunk from the ascending aorta (distance=0 cm). The values for the ascending aorta of Chinese subjects are 16% greater (P<.001). Because R/h is proportional to wall stress (see text), the wall stress distribution along the aorta of Chinese subjects is more uniform, whereas that in the aorta of occidental subjects shows a progressive increase.

	Discussion

Top Abstract Introduction Pulsatile Arterial Function and... Discussion References

 
The effects of genetic and environmental factors on the structure and function of large arteries are relevant to the understanding of the pathophysiology of hypertension and arterial disorders. There is some preliminary indirect evidence that genetic factors are linked to pulsatile pressure, but no conclusive evidence of whether this is related to specific structural aspects of large arteries has been found. Geographic and environmental factors such as dietary salt consumption and exercise have been shown to be related to indexes of arterial wall stiffness such as pulse wave velocity and regional arterial compliance. Structural attributes of the ascending aortic wall may provide an explanation for the difference in prevalence of hypertension among different populations independent of other factors. It is not known, however, whether these attributes are due to genetic factors or other modifying environmental influences in different racial groups.

	References

Top Abstract Introduction Pulsatile Arterial Function and... Discussion References

 

1. Murphy EA. Genetics in hypertension. Circ Res. 1973;32(suppl I):I-129-I-137.
2. Watt GCM, Foy CJW, Hart JT, Bingham G, Edwards C, Hart M, Thomas E, Walton P. Dietary sodium and arterial blood pressure: evidence against genetic susceptibility. Br Med J. 1985;291:1525-1528.
3. Folkow B. Pathophysiology of hypertension: differences between young and elderly. J Hypertens. 1993;11(suppl 4):S21-S24.
4. Maddocks I. Possible absence of essential hypertension in two complete Pacific Island populations. Lancet. 1961;2:396-399. [Medline] [Order article via Infotrieve]
5. Sinnett PF, Whyte HM. Epidemiological studies in a total highland population, Tukisenta, New Guinea. J Chronic Dis. 1973;26:265-290. [Medline] [Order article via Infotrieve]
6. Tripodo NC, Frolich ED. Similarities of genetic (spontaneous) hypertension: man and rat. Circ Res. 1981;48:309-319. [Free Full Text]
7. Limas C, Westrum B, Limas CJ, Cohn JN. Effect of salt on the vascular lesions of spontaneously hypertensive rats. Hypertension. 1980;2:477-489. [Abstract/Free Full Text]
8. Guyton AC, Coleman TG, Cowley AW, Manning RD, Normal RA, Ferguson JD. A systems analysis approach to understanding long-range arterial blood pressure control and hypertension. Circ Res. 1974;35:159-176. [Free Full Text]
9. Folkow B. Physiological aspects of primary hypertension. Physiol Rev. 1982;62:347-504. [Free Full Text]
10. Dubay C, Vincent M, Samani NJ, Hilbert P, Kaiser MA, Beressi J-P, Kotelevtsev Y, Beckmann JS, Soubrier F, Sassard J, Lathrop GM. Genetic determinants of diastolic and pulse pressure map to different loci in Lyon hypertensive rats. Nat Genet. 1993;3:354-357. [Medline] [Order article via Infotrieve]
11. Pang SC, Scott TM. An examination of the arterial media in transplanted arteries of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY). Artery. 1985:12:382-387.
12. Qiao JH, Xie PZ, Fishbein MC, Kreuzer J, Drake TA, Demer LL, Lusis AJ. Pathology of atheromatous lesions in inbred and genetically engineered mice: genetic determination of arterial calcification. Arterioscler Thromb. 1994;14:1480-1497. [Abstract/Free Full Text]
13. Michel JB, Heudes D, Michel O, Poitevin P, Philippe M, Scalbert E, Corman B, Levy BI. Effect of chronic ANG I-converting enzyme inhibition on aging processes, II: large arteries. Am J Physiol. 1994;267:R124-R135. [Abstract/Free Full Text]
14. Levy BI, Michel JB, Salzman JL, Poitevin P, Devissaguet M, Scalbert E, Safar ME. Long-term effects of angiotensin-converting enzyme inhibition on the arterial wall of adult spontaneously hypertensive rats. Am J Cardiol. 1993;71:8E-16E. [Medline] [Order article via Infotrieve]
15. Griffin SA, Brown WCB, MacPherson FF, McGrath JC, Wilson VG, Korsgaard N, Mulvany MJ, Lever AF. Angiotensin II causes hypertrophy in part by a nonpressor mechanism. Hypertension. 1991;17:626-635. [Abstract/Free Full Text]
16. Kato H, Suzuki H, Tajima S, Ogata Y, Tominaga T, Sato A, Saruta T. Angiotensin II stimulates collagen synthesis in cultured vascular smooth muscle cells. J Hypertens. 1991;9:17-22. [Medline] [Order article via Infotrieve]
17. Darlu P, Sagnier P-P, Bois E. Evidences pour une transmission genetique de la pulsatilite arterielle. C R Acad Sci III. 1994;317:62-69. [Medline] [Order article via Infotrieve]
18. Weinberger MH, Miller JZ, Luft FC, Fineberg NS, Grim CE, Christian JC. Genetic aspects of the blood pressure control system. Clin Exp Hypertens. 1981;3:569-581.
19. O'Rourke MF. Arterial Function in Health and Disease. Edinburgh, Scotland: Churchill Livingstone Inc; 1982:276.
20. Francois B, de Paepe A, Matton MT, Clement D. Pulse wave velocity recordings in a family with ecchymotic Ehlers-Danlos syndrome. Int Angiol. 1986;5:1-5. [Medline] [Order article via Infotrieve]
21. Kalath S, Tsipouras P, Silver FH. Increased aortic root stiffness associated with osteogenesis imperfecta. Ann Biomed Eng. 1987;15:91-99. [Medline] [Order article via Infotrieve]
22. Buntin CM, Tsipouras P, Silver FH. Noninvasive assessment of aortic mechanical properties of patients with the Marfan syndrome and osteogenesis imperfecta. In: Proceedings of IEEE/Ninth Annual Conference of the Engineering in Medicine and Biology Society; 1987;1479-1480.
23. Beylot C, Doutre MS, Beylot-Barry M, Busquet M. Arterial involvement in hereditary dysplasia of connective tissue. Rev Med Interne. 1994;15:193-209.[Medline] [Order article via Infotrieve]
24. Hamilton M, Pickering GW, Roberts JAF, Sowry GSC. Aetiology of essential hypertension: arterial pressure in the general population. Clin Sci. 1954;1:13-16.
25. Avolio AP, Chen SG, Wang RP, Zhang CL, Li MF, O'Rourke MF. Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community. Circulation. 1983;68:50-58. [Abstract/Free Full Text]
26. Avolio AP, Deng FQ, Li WQ, Luo YF, Huang ZD, Xing LF, O'Rourke MF. Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China. Circulation. 1985;71:202-210. [Abstract/Free Full Text]
27. Avolio AP, Clyde KM, Beard TC, Cooke HM, O'Rourke MF. Improved arterial distensibility in normotensive subjects on a low salt diet. Arteriosclerosis. 1986;6:166-169. [Abstract/Free Full Text]
28. Draajier P, Kool MJ, Maessen JM, van Bortel LM, de Leeuw PW, van Hooff JP, Leunissen KM. Vascular distensibility and compliance in salt-sensitive and salt-resistant borderline hypertension. J Hypertens. 1993;11:1199-1207. [Medline] [Order article via Infotrieve]
29. Brier ME, Luft FC. Sodium kinetics in white and black normotensive subjects: possible relevance to salt-sensitive hypertension. Am J Med Sci. 1994;307(suppl 1):S38-S42.
30. Flack JM, Ensrud KE, Mascioli S, Launer CA, Svendsen K, Elmer PJ, Grimm RH Jr. Racial and ethnic modifiers of the salt-blood pressure response. Hypertension. 1991;17(suppl I):I-115-I-121.
31. Levenson JA, Simon AC, Maarek BE, Gitelman RJ, Fiessinger JN, Safar ME. Regional compliance of brachial artery and saline infusion in patients with arteriosclerosis obliterans. Arteriosclerosis. 1985;5:80-87. [Abstract/Free Full Text]
32. Vaitkevecius PV, Fleg JL, Engel JH, O'Connor FC, Wright JG, Lakatta LE, Yin FCP, Lakatta EG. Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation. 1993;88:1456-1462. [Abstract/Free Full Text]
33. Cameron JD, Dart AM. Exercise training increases total systemic arterial compliance in humans. Am J Physiol. 1994;266:H693-H701. [Abstract/Free Full Text]
34. Virmani R, Avolio AP, Mergner WJ, Robinowitz M, Herderick EE, Cornhill JF, Guo SY, Liu TH, Ou DY, O'Rourke MF. Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis: comparison between occidental and Chinese communities. Am J Pathol. 1991;139:1119-1129. [Abstract]
35. Avolio A, Corea R, Guo SY, Liu TH, Ou DY, Mergner W, O'Rourke MF, Virmani R. Aortic dimensions in oriental and occidental populations associated with different prevalence of hypertension. J Hypertens. 1994;12(suppl 3):S78. Abstract.

This article has been cited by other articles:

				M. E. Safar, M. Lajemi, A. Rudnichi, R. Asmar, and A. Benetos Angiotensin-Converting Enzyme D/I Gene Polymorphism and Age-Related Changes in Pulse Pressure in Subjects with Hypertension Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 782 - 786. [Abstract] [Full Text] [PDF]

				O. O. Aalami, T. D. Fang, H. M. Song, and R. P. Nacamuli Physiological Features of Aging Persons Arch Surg, October 1, 2003; 138(10): 1068 - 1076. [Full Text] [PDF]

				E. G. Lakatta and D. Levy Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part I: Aging Arteries: A "Set Up" for Vascular Disease Circulation, January 7, 2003; 107(1): 139 - 146. [Full Text] [PDF]

				J.-J. Mourad, G. Ducailar, A. Rudnicki, M. Lajemi, A. Mimran, and M. E Safar Age-related increase of pulse pressure and gene polymorphisms in essential hypertension: a preliminary study Journal of Renin-Angiotensin-Aldosterone System, June 1, 2002; 3(2): 109 - 115. [Abstract] [PDF]

				O. Hanon, V. Luong, J. J. Mourad, L. A. Bortolotto, X. Jeunemaitre, and X. Girerd Aging, Carotid Artery Distensibility, and the Ser422Gly Elastin Gene Polymorphism in Humans Hypertension, November 1, 2001; 38(5): 1185 - 1189. [Abstract] [Full Text] [PDF]

				J. Blacher, A. P. Guerin, B. Pannier, S. J. Marchais, and G. M. London Arterial Calcifications, Arterial Stiffness, and Cardiovascular Risk in End-Stage Renal Disease Hypertension, October 1, 2001; 38(4): 938 - 942. [Abstract] [Full Text] [PDF]

				C. Labat, P. Lacolley, M. Lajemi, M. de Gasparo, M. E. Safar, and A. Benetos Effects of Valsartan on Mechanical Properties of the Carotid Artery in Spontaneously Hypertensive Rats Under High-Salt Diet Hypertension, September 1, 2001; 38(3): 439 - 443. [Abstract] [Full Text] [PDF]

				R. P. Kelly, S. C. Millasseau, J. M. Ritter, and P. J. Chowienczyk Vasoactive Drugs Influence Aortic Augmentation Index Independently of Pulse-Wave Velocity in Healthy Men Hypertension, June 1, 2001; 37(6): 1429 - 1433. [Abstract] [Full Text] [PDF]

				J. Blacher, A. P. Guerin, B. Pannier, S. J. Marchais, M. E. Safar, and G. M. London Impact of Aortic Stiffness on Survival in End-Stage Renal Disease Circulation, May 11, 1999; 99(18): 2434 - 2439. [Abstract] [Full Text] [PDF]

				J. Blacher, B. Pannier, A. P. Guerin, S. J. Marchais, M. E. Safar, and G. M. London Carotid Arterial Stiffness as a Predictor of Cardiovascular and All-Cause Mortality in End-Stage Renal Disease Hypertension, September 1, 1998; 32(3): 570 - 574. [Abstract] [Full Text] [PDF]

				L. P. Svetkey, Y.-T. Chen, S. P. McKeown, L. Preis, and A. F. Wilson Preliminary Evidence of Linkage of Salt Sensitivity in Black Americans at the ß2-Adrenergic Receptor Locus Hypertension, April 1, 1997; 29(4): 918 - 922. [Abstract] [Full Text]

				L. P. Svetkey, S. P. McKeown, and A. F. Wilson Heritability of Salt Sensitivity in Black Americans Hypertension, November 1, 1996; 28(5): 854 - 858. [Abstract] [Full Text]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Avolio, A. Search for Related Content PubMed PubMed Citation Articles by Avolio, A.