(Hypertension. 1997;29:583-586.)
© 1997 American Heart Association, Inc.
Articles |
Combined Effects of Hypertension and Hypercholesterolemia on Radial Artery Function
Cattedra di Medicina Interna I, Universita di Milano and Ospedale S. Gerardo Monza; Centro di Fisiologia Clinica e Ipertensione, Universita di Milano and Ospedale Maggiore, Milano; and Centro Auxologico Italiano, Milano, Italy.
Correspondence to Prof Giuseppe Mancia, Medicina Interna I, Universita di Milano, Ospedale S. Gerardo Monza, Via Donizetti 106, Monza (Milano), Italy.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Compliance and distensibility of middle-sized conduit arteries are increased in hypertension and reduced in hypercholesterolemia. Despite their frequent association in the same individual, the combined effect of these two conditions on arterial mechanical properties is unknown. We studied four groups of age- and sex-matched subjects: 10 normotensive normocholesterolemic subjects, 10 mild hypertensive normocholesterolemic subjects, 10 mild hypercholesterolemic normotensive subjects, and 10 mild hypertensive and mild hypercholesterolemic subjects. We measured radial artery diameter by an echotracking device and beat-to-beat blood pressure from an ipsilateral finger. Compliance-pressure and distensibility-pressure curves were derived by Langewouters' formula. Between-group comparisons were made by calculating for both compliance and distensibility the integral of the area under the portion of the curve common to the four groups ("isobaric" compliance and distensibility). Blood pressure was similarly elevated in the two hypertensive groups, and serum cholesterol was similarly elevated in the two hypercholesterolemic groups. Compared with values in normotensive normocholesterolemic subjects, isobaric compliance and distensibility were greater in hypertensive normocholesterolemic (+38% and 47%, respectively) and smaller in normotensive hypercholesterolemic (-6% and -23%) subjects. However, when both hypertension and hypercholesterolemia were present, isobaric compliance and isobaric distensibility were significantly reduced (-26% and -18%, P<.05). Therefore, hypercholesterolemia reverses the effect of hypertension on arterial compliance and causes arterial stiffening, as when present alone.
Key Words: compliance • hypercholesterolemia • atherosclerosis
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Previous studies have shown that when measured in muscle arteries, arterial compliance and distensibility are affected in opposite directions by hypercholesterolemia and hypertension1 2 3 4 ; that is, for a given blood pressure (BP) value, compliance and distensibility are reduced in subjects with an elevated serum cholesterol1 2 and increased in subjects with a mild or moderate BP elevation.3 4 No information exists on the effect of combined hypercholesterolemia and hypertension on arterial compliance and distensibility, despite the frequent coexistence of these conditions in the same person. Therefore, we addressed this issue in the present study.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Subjects
We studied 40 outpatients ranging in age from 39 to 76 years. The subjects were 10 normotensive normocholesterolemic healthy control subjects, 10 normotensive hypercholesterolemic subjects, 10 hypertensive normocholesterolemic subjects, and 10 hypertensive hypercholesterolemic subjects. BP values were measured during two visits made 2 weeks apart with the use of a mercury sphygmomanometer and with the subject in the sitting position for at least 5 minutes. Serum cholesterol was measured at the second visit from a blood sample withdrawn from an antecubital vein. Hypertensive subjects were included if after washout from treatment (see below) their diastolic BP was between 90 and 114 mm Hg. Hypercholesterolemic subjects were included if their total serum cholesterol was higher than 250 mg/dL. Subjects were excluded from the study if they had a history of cardiovascular disease; evidence of cardiac, renal, or cerebral damage at routine clinical and laboratory examinations; or evidence of atherosclerotic plaques restricting the arterial lumen by more than 30% at carotid and femoral echo-Doppler examinations. No hypercholesterolemic subject was taking lipid-lowering drugs. Hypertensive subjects who were taking antihypertensive drugs stopped taking the drugs 2 weeks before the study (see below). All subjects volunteered to participate in the study after being informed of its nature and purpose. The study protocol was approved by the Ethics Committees of the institutions involved.
Arterial Compliance and Distensibility
Arterial compliance and distensibility were measured in the left radial artery by an A-mode, ultrasonic, echotracking device (NIUS01, Asulab and Capital Medical Service) as described in detail in previous studies.1 2 3 4 5 6 7 8 9 Briefly, with the subject supine and the arm fixed at the heart level, a 10-MHz probe was positioned over the radial artery, 2 to 4 cm above the wrist, and oriented perpendicularly to the longitudinal axis of the artery by use of the Doppler signal as a guide. Direct contact with the skin and arterial deformation were prevented by use of an ultrasonic gel. After the switch to A-mode, the backscattered echoes from the inner anterior and posterior walls were visualized on a screen, and the related radiofrequency signals were peaked by an electronic tracer, the displacement of which allowed evaluation of the vessel diameter at 50 Hz.10 Continuous (analog) recording of radial artery diameter was coupled with continuous (analog) recording of BP by a finger pressure device (Finapres 2300, Ohmeda) positioned on the middle finger of the ipsilateral hand and capable of providing BP values similar to the ones taken invasively from the radial artery.11 Both signals were stored (fast analog/digital transformer) and digitized for continuous display on the screen. The arterial diameter and BP signals were sent to a computer programmed to provide diameter-pressure curves over the BP values from diastole to systole obtained by the finger recording. The curve was then analyzed according to its fit with the arc tangent model of Langewouters, which is based on the following formula:
 |
, ß, and 
are three optimal parameters describing the spatial position of the diameter-pressure curve.12 From this formula, cross-sectional compliance (C=
S/P10 ) can be calculated as
 |
Other Measurements
Heart rate values were obtained via the finger pressure signal as the reciprocal of the interval between consecutive systolic beats. The venous blood sample was used for measurement of not only total serum cholesterol but also high-density lipoprotein cholesterol and triglycerides and calculation of low-density lipoprotein cholesterol.
Protocol and Data Analysis
The study was conducted in the morning after subjects had abstained 24 hours from cigarette smoking and alcohol and caffeine consumption. The protocol of the study was as follows: (1) Each subject was placed in the supine position and fitted with the finger pressure and echotracking devices; (2) after 20 minutes, BP, heart rate, radial artery diameter, radial artery compliance, and radial artery distensibility were continuously measured for 15 minutes. To obtain baseline values, we averaged each variable first over 4-second periods and then for five 4-second periods taken at 3-minute intervals. Diameter-pressure curves, compliance-pressure curves, and distensibility-pressure curves from individual subjects were summed and expressed as mean curves for each group. Average values were also obtained for (1) radial artery diameter at the diastolic BP value, (2) the integral of the area under the curve relating compliance to the BP values common to the four groups, referred to as the isobaric compliance index; and (3) the integral of the area under the curve relating distensibility to the BP values common to the four groups, referred to as the isobaric distensibility index. We used isobaric compliance and distensibility indexes for statistical comparisons between groups. The statistical significance of between-group differences was assessed by two-way ANOVA. We used Student's unpaired two-tailed t test with the Bonferroni correction to identify differences between groups. A value of P<.05 was taken as the level of statistical significance.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
As shown in the Table
, the number of men and women was similar in the four groups. Age was slightly greater in the two hypertensive than the two normotensive groups, but the differences were not statistically significant. Body surface area was superimposable in the four groups, whereas as expected, BP (sphygmomanometric values) and total cholesterol, serum low-density lipoprotein cholesterol, and triglycerides were significantly greater in the two hypertensive and two hypercholesterolemic groups, respectively. Finger BP values were lower than sphygmomanometric values but similarly higher in the two hypertensive than in the normotensive groups. Heart rate and serum high-density lipoprotein cholesterol were not significantly different in the four groups.
|
The top panels of the Figure show that in all groups, radial artery diameter increased progressively and slightly from diastolic to systolic finger BP and that diameter-pressure curves and diameter values at diastolic BP were significantly greater in normotensive normocholesterolemic than in hypertensive hypercholesterolemic subjects, the remaining two groups showing intermediate values. In all groups, radial artery compliance-pressure curves decreased progressively and markedly from diastolic to systolic BP (Figure, middle). Compared with the curve in normotensive normocholesterolemic subjects, the compliance-pressure curve was (1) displaced upward in hypertensive normocholesterolemic subjects, (2) displaced slightly downward in normotensive hypercholesterolemic subjects, and (3) displaced markedly downward in hypertensive hypercholesterolemic subjects. The differences in isobaric compliance index between normotensive normocholesterolemic, hypertensive normocholesterolemic, and hypertensive hypercholesterolemic subjects were statistically significant. Similar findings were obtained for isobaric radial artery distensibility, which, however, was reduced to a similarly marked degree in normotensive hypercholesterolemic and hypertensive hypercholesterolemic subjects (Figure, bottom).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Our study confirms that isobaric radial artery compliance and distensibility are increased in hypertensive3 4 and reduced in hypercholesterolemic1 2 subjects. However, it also provides the first evidence that when both hypertension and hypercholesterolemia are present, isobaric radial artery compliance and distensibility are reduced and that therefore the effect of an increase in serum cholesterol on arterial elasticity prevails over that of an increase in BP. This has a practical relevance because hypertension and hypercholesterolemia are frequently present in the same individual, particularly when, as was the case in our study, the BP and serum cholesterol elevations are both mild.14 15
The mechanisms responsible for the changes in radial artery compliance and distensibility occurring in hypertension and hypercholesterolemia have never been satisfactorily elucidated. It has been suggested, however, that arterial compliance is increased in hypertension because of an increase in vascular smooth muscle at the expense of stiffer tissue components such as collagen.3 4 5 16 It has also been suggested that arterial compliance is reduced in hypercholesterolemia because of (1) an increased content of collagen and calcium subsequent to deposition of lipids in the intima,17 (2) a cholesterol-dependent impairment in the secretion of endothelial factors that cause smooth muscle relaxation,2 18 and (3) a potentiating effect of elevated cholesterol levels on the responsiveness of vascular smooth muscle to sympathetic stimuli, leading to an increased smooth muscle contraction.19 20 This is because smooth muscle relaxation and contraction are accompanied by an increase and reduction in radial artery compliance, respectively,9 as is also the case when alterations in sympathetic modulation of radial artery tone are involved.9 Irrespective of the nature of the factors involved, it is obvious that the reduction in arterial compliance and distensibility associated with hypercholesterolemia prevents or supersedes the effect of hypertension on conduit artery mechanics.3 4 5 16
Three other points should be mentioned. First, the four groups of subjects had somewhat different ages; however, the differences were not statistically significant. Furthermore, the effects of cholesterolemia on arterial compliance were similar in the group with the youngest subject and in that with the oldest. Finally, age has been shown to have no substantial effect on peripheral artery mechanics.21 Thus, aging per se cannot account for our results. Second, our study did not address the question of the effect of combined hypertension and hypercholesterolemia on large elastic arteries because in these arteries, in situ or nearby BP cannot be easily measured, and thus reliable compliance-pressure and distensibility-pressure curves cannot be properly obtained.21 However, although not always unequivocal,22 studies that have made use of techniques different from the dynamic one used in the present investigation suggest that in middle and large elastic arteries, elevations in both BP and serum cholesterol reduce arterial compliance.23 24 25 26 27 It is therefore reasonable to speculate that their association in the same individual is accompanied by a reduction of large-artery compliance and distensibility even more pronounced than that seen at the radial artery level. Finally, changes in arterial compliance may affect atherogenesis by absorbing to a greater or lesser extent the traumatic effect of BP on the vessel wall, as shown by the marked increase in atherosclerosis that follows experimental reduction of arterial compliance in animals.28 29 30 In this context, it can be speculated that the increase in arterial compliance associated with hypertension delays atherogenesis and that this favorable effect is lost by the concomitant occurrence of mild hypercholesterolemia.
Received April 25, 1996;
first decision May 24, 1996;
first decision September 9, 1996;
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Giannattasio C, Mangoni AA, Failla M, Carugo S, Stella ML, Stefanoni P, Grassi G, Vergani C, Mancia G. Impaired radial artery compliance in normotensive subjects with familial hypercholesterolemia. Atherosclerosis. 1996;124:249-260.[Medline] [Order article via Infotrieve]
2.
Hayoz D, Weber R, Rutschmann B, Darioli R, Burnier M, Waeber B, Brunner HR. Post-ischemic blood flow response in hypercholesterolemic patients. Hypertension. 1995;26:497-502.
3. Laurent S, Hayoz D, Trazzi S, Boutouyrie P, Waeber B, Omboni S, Brunner HR, Mancia G, Safar M. Isobaric compliance of the radial artery is increased in patients with essential hypertension. J Hypertens. 1993;11:89-98.[Medline] [Order article via Infotrieve]
4.
Hayoz D, Rutschmann B, Perret F, Niedelberger M, Tardy Y, Mooser V, Nussberger J, Waeber B, Brunner HR. Conduit artery compliance and distensibility are not necessarily reduced in hypertension. Hypertension. 1992;20:1-6.
5.
Laurent S, Girerd X, Mourad JJ, Boutouyrie P, Safar M. Elastic modulus of the radial artery wall is reduced in hypertensives. Arterioscler Thromb. 1994;14:1223-1231.
6. Giannattasio C, Failla M, Stella ML, Mangoni AA, Carugo S, Pozzi M, Grassi G, Mancia G. Alterations of radial artery compliance in patients with congestive heart failure. Am J Cardiol. 1995;76:381-385.[Medline] [Order article via Infotrieve]
7. Giannattasio C, Mangoni AA, Stella ML, Carugo S, Grassi G, Mancia G. Acute effects of smoking on radial artery compliance in humans. J Hypertens. 1994;12:691-696.[Medline] [Order article via Infotrieve]
8.
Giannattasio C, Failla M, Stella ML, Mangoni AA, Turrini D, Carugo S, Pozzi M, Grassi G, Mancia G. Angiotensin-converting enzyme inhibition and radial artery compliance in patients with congestive heart failure. Hypertension. 1995;26:491-496.
9.
Grassi G, Giannattasio C, Failla M, Pesenti A, Peretti G, Marinoni E, Fraschini M, Vailati S, Mancia G. Sympathetic modulation of radial artery compliance in congestive heart failure. Hypertension. 1995;26:348-354.
10. Tardy Y, Meister JJ, Perret F, Brunner HR, Arditi M. Non invasive estimate of the mechanical properties of peripheral arteries from ultrasonic and photoplethysmographic measurements. Clin Phys Physiol Meas. 1991;3:360-367.
11.
Parati G, Casadei R, Groppelli A, Di Rienzo M, Mancia G. Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing. Hypertension. 1989;13:647-655.
12. Langewouters GJ, Zwart A, Busse R, Wesseling KH. Pressure diameter relationship of segments of human finger arteries. Clin Phys Physiol Meas. 1986;7:43-45.[Medline] [Order article via Infotrieve]
13. Girerd X, Mourad JJ, Acar C, Heudes D, Chiche S, Bruneval P, Mignot JP, Billaud E, Safar M, Laurent S. Non invasive measurement of medium size artery wall thickness in humans: in vitro validation. J Vasc Res. 1994;31:114-120.[Medline] [Order article via Infotrieve]
14.
Hypertension Detection and Follow-up Program Cooperative Group. Five-year findings of the HDFP: reduction in mortality of persons with high blood pressure, including mild hypertension. JAMA. 1979;242:2562-2571.
15. Kannel B, Castelli WP, Gordon T. Cholesterol in the prediction of the atherosclerotic disease: new perspectives based on the Framingham Study. Ann Intern Med. 1979;90:85-91.
16. Girerd X, Mourad JJ, Copie X, Moulin C, Acar C, Safar M, Laurent S. Non invasive detection of vascular hypertrophy in untreated and treated hypertensive patients. Am J Hypertens. 1994;7:1076-1084.[Medline] [Order article via Infotrieve]
17.
Ross R, Glomset J. Atherosclerosis and the arterial muscle cells: proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science. 1973;180:1332-1339.
18. Chowienczyk PJ, Watts GF, Cockcroft JR, Ritte JR. Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolemia. Lancet. 1992;340:1430-1432.[Medline] [Order article via Infotrieve]
19. Asada Y, Yamamoto R, Takasaki K, Sumiyoshi A. Vascular contraction in perfused carotid arteries of cholesterol-fed rabbits. Atherosclerosis. 1992;94:233-239.[Medline] [Order article via Infotrieve]
20. Dupoy P, Geshwind HJ, Pelle G, Gallot D, Dubois Rande JL. Assessment of coronary vasomotor tone by intracoronary ultrasound. Am J Hypertens. 1993;126:76-85.
21. Kawasaki T, Sasayama S, Yagi SI, Asakawa T, Hirai T. Non invasive assessment of the age-related changes in stiffness of major branches of the human arteries. Cardiovasc Res. 1987;21:678-687.[Medline] [Order article via Infotrieve]
22.
O'Rourke G. Mechanical principle in arterial disease. Hypertension. 1995;26:2-9.
23.
Roman MJ, Saba PS, Pini R, Spitzer M, Pickering TG, Rosen S, Albermann M, Devereux R. Parallel cardiac and vascular adaptation in hypertension. Circulation. 1992;86:1909-1918.
24.
Riley WA, Freedmann DS, Higgs NA, Barnes RW, Zinkgraf SA, Berenson GS. Decreased arterial elasticity associated with cardiovascular disease risk factors in the young: Bogalusa Heart Study. Arteriosclerosis. 1986;6:378-386.
25.
Farrar DJ, Bond MG, Riley WA, Sawyer JK. Anatomic correlates of aortic pulse wave velocity and carotid artery elasticity during atherosclerosis progression and regression in monkeys. Circulation. 1991;83:1754-1763.
26. Newman DL, Gosling RG, Bowden NLR. Changes in aortic distensibility and area ratio with the development of atherosclerosis. Atherosclerosis. 1971;14:231-240.[Medline] [Order article via Infotrieve]
27. Dart AM, Lacombe F, Yeoh JK, Cameron JD, Jennongs GL, Laufer E, Esmone DS. Aortic distensibility in patients with isolated hypercholesterolemia, coronary artery disease or cardiac transplant. Lancet. 1991;338:270-273.[Medline] [Order article via Infotrieve]
28. Booth RFG, Martin JF, Honey AC, Hassal DG, Beesley JE, Moncada S. Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular manipulation. Atherosclerosis. 1989;76:257-268.[Medline] [Order article via Infotrieve]
29. Baron BW, Glagov S, Giddens DP, Zarins CK. Effect of coarctation on matrix content of experimental aortic atherosclerosis: relation to location, plaque size and blood pressure. Atherosclerosis. 1993;102:37-49.[Medline] [Order article via Infotrieve]
30. Bassiouny HS, Zarins CK, Kadowaki NH, Glagov S. Hemodynamic stress and experimental aortoiliac atherosclerosis. J Vasc Surg. 1994;19:426-434.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  E. M. Urbina, R. V. Williams, B. S. Alpert, R. T. Collins, S. R. Daniels, L. Hayman, M. Jacobson, L. Mahoney, M. Mietus-Snyder, A. Rocchini, et al. Noninvasive Assessment of Subclinical Atherosclerosis in Children and Adolescents: Recommendations for Standard Assessment for Clinical Research: A Scientific Statement From the American Heart Association Hypertension, November 1, 2009; 54(5): 919 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Laurent, J. Cockcroft, L. Van Bortel, P. Boutouyrie, C. Giannattasio, D. Hayoz, B. Pannier, C. Vlachopoulos, I. Wilkinson, H. Struijker-Boudier, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications Eur. Heart J., November 1, 2006; 27(21): 2588 - 2605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Dart, C. D. Gatzka, J. D. Cameron, B. A. Kingwell, Y.-L. Liang, K. L. Berry, C. M. Reid, and G. L. Jennings Large Artery Stiffness Is Not Related to Plasma Cholesterol in Older Subjects with Hypertension Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 962 - 968. [Abstract] [Full Text]
|
|
|
|
 |
|
 I. B. Wilkinson, K. Prasad, I. R. Hall, A. Thomas, H. MacCallum, D. J. Webb, M. P. Frenneaux, and J. R. Cockcroft Increased central pulse pressure and augmentation index in subjects with hypercholesterolemia J. Am. Coll. Cardiol., March 20, 2002; 39(6): 1005 - 1011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Giannattasio, M. Failla, A. Grappiolo, M. L. Stella, A. Del Bo, M. Colombo, and G. Mancia Fluctuations of Radial Artery Distensibility Throughout the Menstrual Cycle Arterioscler Thromb Vasc Biol, August 1, 1999; 19(8): 1925 - 1929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-J. Mourad, X. Girerd, P. Boutouyrie, S. Laurent, M. Safar, and G. London Increased Stiffness of Radial Artery Wall Material in End-Stage Renal Disease Hypertension, December 1, 1997; 30(6): 1425 - 1430. [Abstract] [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||