© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Carotid Intimal-Medial Thickness and Stiffness Are Not Affected by Hypercholesterolemia in Uncomplicated Essential Hypertension
From the Department of Medicine (M.J.R., R.B.D.), New York Hospital–Cornell Medical Center, New York, NY; the Institute of Clinical Medicine (P.S.S., A.G.), University of Sassari, Sassari, Italy; the Institute of Internal Medicine (C.L., D.S.), University of Ferrara, Ferrara, Italy; and the Division of Gerontology and Geriatrics (R.P.), University of Firenze, Firenze, Italy.
Correspondence to Mary J. Roman, MD, Division of Cardiology, New York Hospital–Cornell Medical Center, 525 E 68th St, New York, NY 10021. E-mail mroman{at}mail.med.cornell.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Abstract—The combined effects of hypertension and hypercholesterolemia on carotid anatomy and stiffness were studied in 62 normotensives, 141 uncomplicated essential hypertensives with a total cholesterol level <240 mg/dL, and 60 essential hypertensives with a total cholesterol level
240 mg/dL. Carotid ultrasonography was
performed to evaluate intimal-medial thickness (IMT), relative wall
thickness, and the presence of plaque. Carotid pressure waveforms were
recorded by applanation tonometry to measure carotid stiffness
(ß) and pressure wave reflection (ie, augmentation index). After
adjusting for age, body mass index, and smoking habit by
analysis of covariance, no significant differences were
found between normocholesterolemic hypertensives and
hypercholesterolemic hypertensives in terms of IMT
(0.79±0.19 versus 0.81±0.19 mm), relative wall thickness
(0.27±0.07 versus 0.28±0.07), carotid stiffness (6.1±3.2 versus
5.6±2.7), augmentation index (18.7±12.9% versus 17.3±12.8%), and
prevalence of plaque (30.8% versus 30.7%). In the whole population,
carotid IMT was significantly related to age (r=0.43),
systolic (r=0.35) and diastolic
(r=0.35) blood pressures, body surface area
(r=0.22), and cholesterol levels
(r=0.22) (all P<0.05). Carotid stiffness
was significantly related to age, blood pressure, body mass index, and
body surface area but not to cholesterol levels. In
multivariate analyses, age, body surface area,
and systolic blood pressure, but not cholesterol,
smoking habit, or sex, were independent correlates of IMT (multiple
R=0.54, P<0.0001), whereas carotid
stiffness was independently associated with age, body surface area, and
sex (R=0.38, P<0.0001). In conclusion,
hypertension is a potent stimulus of vascular hypertrophy.
The superimposition of hypercholesterolemia
does not substantially augment these changes or further increase
arterial stiffness in uncomplicated hypertensive
subjects.
Key Words: hypertension • hypercholesterolemia • carotid arteries • atherosclerosis • arterial tonometry
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Hypertension and hypercholesterolemia are major risk factors for cardiovascular morbidity and mortality in Western countries.1 2 Both conditions are common in the general population and are frequently associated, thereby steeply increasing the risk of overall and coronary heart disease mortality.1 Identification of patients at high risk by detection of preclinical disease, when target-organ damage may be in an early and potentially reversible stage, has been emphasized in recent years as a key step in the prevention of major clinical events.3 Previous reports have shown a close relationship between carotid atherosclerosis and both cerebrovascular and coronary artery disease,4 5 suggesting that carotid artery evaluation may help to identify high-risk subjects. However, carotid plaque may represent a late stage in the evolution of atherosclerotic disease in several vascular beds.6 7 8
The recent availability of high-resolution ultrasound techniques allows the detection of early arterial modifications, such as intimal-medial thickening, which may precede the development of atherosclerotic plaques. Previous reports have indicated that carotid intimal-medial thickening is associated with coronary artery disease9 10 and cardiovascular morbidity and mortality.11 12 13 14 15 Moreover, carotid intimal-medial thickening has been described in association with hypertension16 17 and hypercholesterolemia.18 19 Studies of hypercholesterolemia have, however, included subjects with mild hypertension and/or symptomatic cardiovascular disease, and thus, they could not assess the independent contributions of uncomplicated hypertension and hypercholesterolemia to intimal-medial thickening.
Although arterial stiffening has been described in animals with diet-induced hypercholesterolemia in association with structural arterial modifications,20 21 few data are presently available on the effect of hypercholesterolemia on arterial viscoelastic properties in humans. Because an increased pulse wave velocity has been described in hypercholesterolemic monkeys,21 an earlier return of reflected pressure waves to the central aorta in hypercholesterolemia may augment central systolic blood pressure22 and thereby ventricular afterload. This study evaluated a population of uncomplicated hypertensive patients with normal and high cholesterol levels to assess the relative contribution of hypercholesterolemia to carotid structural and functional modifications associated with hypertension.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Study Population
The study is a retrospective evaluation of a population of 395 normotensive and uncomplicated hypertensive subjects enrolled in a cooperative study of preclinical cardiovascular disease in hypertension conducted at Cornell University Medical Center, New York, NY; the Institute of Clinical Medicine, University of Sassari, Sassari, Italy; and the Institute of Internal Medicine, University of Ferrara, Ferrara, Italy. Exclusion criteria were a history or clinical signs of coronary artery disease, heart failure, or valvular heart disease; secondary hypertension; diabetes mellitus; and renal insufficiency. Hypertension was defined as a cuff blood pressure
140 mm Hg systolic and/or 90
mm Hg diastolic on repeated measurements taken by mercury
sphygmomanometry. Sixty-two normotensive,
normocholesterolemic subjects and 201 uncomplicated
essential hypertensives were selected from this population, based on
the availability of cholesterol data. All antihypertensive
drug therapy was stopped at least 3 weeks before the study in the 116
(58%) patients who had been on antihypertensive treatment. None of the
patients were on lipid-lowering therapy.
The effect of hypercholesterolemia in
association with hypertension on carotid structure and stiffness was
evaluated by dividing the study population into 3 groups:
normal-cholesterol normotensives,
normal-cholesterol hypertensives, and
high-cholesterol hypertensives, on the basis of a normal to
borderline-high (<6.22 mmol/L, or 240 mg/dL) or a high
(6.22 mmol/L) fasting total serum cholesterol level
obtained within 1 month of the vascular examination.23
Body habitus was evaluated by body mass index (BMI, weight in kilograms
per square of height in meters squared) and body surface area (BSA,
obtained from height and weight measurements by standard nomograms).
The study protocol was approved by the Committee on Human Rights in
Research of Cornell University Medical College in 1989 and at intervals
thereafter and by the Ethics Committees of the Universities of Sassari
and Ferrara.
Carotid Ultrasonography
Carotid ultrasonography was performed in subjects recruited in
New York (n=199) by using a Biosound Genesis II system (OTE
Biomedica) equipped with a 7.5-MHz probe; subjects recruited in
Sassari (n=43) and Ferrara (n=21) were examined with a Toshiba 270 HG
system equipped with a 7.5-MHz probe. With the subject in the supine
position and the neck in slight hyperextension, the common carotid
artery, carotid bulb, and the extracranial portions of internal and
external carotid arteries were identified. Two-dimensionally guided
M-mode tracings of the distal common carotid artery (
1 cm proximal
to the carotid bulb) were obtained with simultaneous ECG
and contralateral carotid pressure waveform tracings (see below) and
recorded on 1/2-in. Super VHS videotape. After the videotape
was reviewed, suitable frames for measurement of M-mode images were
obtained by using a frame grabber (Imaging Technology Inc) interfaced
with a high-resolution (640x480 pixels) video monitor and stored on
diskette.
Carotid measurements were performed on the stored images by using mouse-driven software written by 1 of the investigators (R.P.), after calibration for depth and time. The simultaneous carotid pressure tracing (see below) was used to time the carotid artery measurement at end diastole (minimum arterial pressure) and at the time of peak systolic pressure. Measurements included the combined intimal-medial thickness (IMT) of the far wall at end diastole, as have been validated in anatomic correlation studies,24 and end-diastolic and peak systolic internal dimensions obtained by continuous tracing of the intima-lumen interface of the near and far walls. All measurements were performed on several cycles and averaged.
Relative wall thickness (RWT) of the artery was calculated according to
the formula 2xfar-wall diastolic
thickness/end-diastolic diameter. Because increased
distending pressure, as occurs in hypertensive patients, could decrease
the IMT due to vessel wall stretching, carotid intimal-medial
cross-sectional area was also calculated as {[(diastolic
diameter/2)+far-wall diastolic
thickness]2x
}-[(diastolic
diameter/2)2x] as an estimate of
circumferential intimal-medial tissue mass.17 25 Both
carotid arteries were scanned to identify the presence and size of
atherosclerotic plaques, defined as focal increases in IMT >50% of
the surrounding wall; standard wall thickness measurements were never
obtained at the level of a discrete plaque.
To minimize operator variability, ultrasonography and tonometry were always performed in each center under the guidance of the same operator (M.J.R., P.S.S., D.S.), and measurements of carotid anatomy were carried out by 2 investigators (M.J.R. for the New York data and P.S.S. for the Sassari and Ferrara data). As previously reported, intraobserver (r=0.98, SEE=0.04 mm for both) and interobserver (r=0.97, SEE= 0.05 mm) reproducibility of blinded wall thickness measurements between the 2 readers was high.16
Carotid Stiffness
In association with carotid ultrasonography, carotid pressure
waveforms were obtained as described elsewhere26 27 28 by
using a high-fidelity external pressure transducer (Millar Instruments,
Inc) applied to the skin overlying the pulse of the contralateral
common carotid artery.
The transducer is internally calibrated (0.2 V/100 mm Hg) and registers absolute changes in applied pressure over a range of 300 mm Hg. To obtain actual carotid blood pressure values, the waveforms require additional external calibration. Based on the observation that mean arterial pressure is nearly identical in all capacitance vessels,29 30 31 brachial artery pressure was measured by the cuff and mercury sphygmomanometer method with the patient in the supine position, and mean pressure was calculated as diastolic blood pressure+(1/3xpulse pressure). The resultant value was assigned to the planimetrically computer-derived mean blood pressure of the carotid waveforms with software written by 1 of the investigators (R.P.). Carotid artery stiffness was estimated by Young’s modulus and the stiffness index. Young’s modulus (E; wall tension per centimeter of thickness for a 100% diameter increase) was calculated according to the formula E=[(Ps-Pd)/(Ds-Dd)]x(D/h), where Ps and Pd are systolic and diastolic pressures, respectively; Ds and Dd are systolic and diastolic carotid dimensions, respectively; and D and h are carotid mean diameter and wall thickness, respectively.32 Carotid stiffness was also calculated by the pressure-independent stiffness index ß according to the formula33 34 ß=[ln(Ps/Pd)]/[(Ds-Dd)/Dd]. This index takes into account the logarithmic relation between arterial pressure and diameter.
Pressure Wave Reflection
The systolic portion of the carotid waveform was
analyzed to calculate the augmentation index,35 36
a means of quantifying the contribution of reflected pressure waves to
the central pulse pressure. After identification of the early and late
systolic peaks and the inflection that separates them,
pressures were determined at peak systolic pressure
(Ppk) and at the inflection point
(Pi) by using the previously described calibrated
computer system. The augmentation index was calculated as
(Ppk-Pi)/pulse pressure
(when Ppk occurred in late systole) or as
(Pi-Ppk)/pulse pressure
(when Ppk occurred in early
systole).36 Pulse wave analysis was performed by a
single investigator (P.S.S.); measurements were repeated on several
cycles and averaged.
Plasma Lipid Determinations
Total cholesterol and triglycerides were
determined by standard enzymatic methods; the HDL
cholesterol fraction was determined after precipitation of
apolipoprotein B–containing lipoproteins, and LDL
cholesterol was calculated as described by Friedewald et
al.37 Hypercholesterolemia was
defined as total cholesterol 6.22 mmol/L (240
mg/dL).23
Statistical Analysis
Data were stored and analyzed by using the
Crunch4 Statistical Package (Crunch Software Corp).
Relationships between continuous variables were evaluated by linear
regression analyses. Comparisons between normotensive and
hypertensive subjects were performed by Student’s t test.
Carotid anatomy and stiffness were compared among
normal-cholesterol normotensives and normal- and
high-cholesterol hypertensives by ANOVA. ANCOVA was also
performed to compare groups after controlling for differences in age,
BSA, and smoking habit. Both analyses were followed by the
Ryan, Einot, Gabriel, and Welsch F test multiple-comparison procedure.
Power analysis was performed to assess the minimal difference
in IMT detectable in our study. Based on the size of our groups and
within-group SDs, differences as small as 0.07 mm for the IMT were
detectable between normal and high-cholesterol
hypertensives with an 
error of 0.05 and a statistical power of
0.90; this detectable difference is lower than the absolute
between-group difference in IMT associated with a significantly higher
risk of cardiovascular and/or cerebrovascular
events.38 39 Multiple regression analyses
were performed to assess independent determinants of carotid
intimal-medial cross sectional area and the stiffness index in
normotensive and hypertensive subjects. Data are expressed as mean±SD.
A 2-tailed P value <0.05 was considered significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Characteristics of Normotensive and Hypertensive Subjects
Among the 201 hypertensive patients, 141 had total cholesterol levels <6.22 mmol/L (240 mg/dL), while 60 had a total cholesterol level
6.22 mmol/L (Table 1
). Hypertensive patients with
higher cholesterol levels were significantly older than
normocholesterolemic hypertensive and normotensive
subjects. Both hypertensive groups had significantly greater body
weights and BMIs than did normotensives, while the distribution of sex
and height was similar among the groups. BSA was significantly greater
in normocholesterolemic hypertensives than in
normotensive subjects. Both hypertensive groups had similar blood
pressure levels, and the normocholesterolemic groups
did not differ in total and LDL cholesterol. The total-HDL
ratio was significantly increased in
hypercholesterolemic hypertensives.
Hypercholesterolemic hypertensives were more likely to
be current or former smokers.
|
Carotid Anatomy and Stiffness in Normal- and
High-Cholesterol Hypertensive Patients
Carotid wall thickness, RWT, cross-sectional area, and prevalence
of plaque were significantly greater in both hypertensive groups than
in the normotensive subjects, while normal- and
high-cholesterol hypertensives did not differ in these
parameters (Table 2). Neither
the stiffness index nor Young’s elastic modulus differed significantly
among the 3 groups, whereas the augmentation index was similarly higher
in both hypertensive groups than in normotensive subjects. ANCOVA,
after controlling for differences in age, BSA, and smoking habit,
yielded similar results (Table 2, values in parentheses). To
avoid a potentially inadequate adjustment for age in ANCOVA, each
hypertensive group was also stratified by age into 2 subsets (<50 and
50 years); carotid parameters were then analyzed
in relation to the cholesterol levels. There were no
significant differences between the 2 subgroups comparable by age but
different in cholesterol level. For example, mean carotid
IMT was 0.75±0.17 and 0.71±0.16 mm in
hypercholesterolemic and
normocholesterolemic patients <50 years old and
0.88±0.19 and 0.85±0.19 mm in older
hypercholesterolemic and
normocholesterolemic patients (P=0.38 and
0.40, respectively).
|
Univariate Correlates of Carotid Anatomy and
Stiffness Parameters in Normotensive and Hypertensive
Subjects
In the entire population (upper portion of Table 3), carotid wall thickness and
cross-sectional area were directly and significantly related to total
and LDL cholesterol, age, BMI, BSA, and systolic
and diastolic blood pressures. Similarly, RWT was directly
related to cholesterol levels, age, BMI, and
systolic pressure but not to BSA or diastolic blood
pressure (Table 3). Carotid lumen diameter was most closely
related to older age and higher blood pressure. Young’s modulus was
significantly related to age and systolic blood pressures and
negatively to BMI and BSA. The stiffness index was directly related to
age and negatively to BSA; no stiffness index showed a significant
relationship with cholesterol levels. Similar results were
obtained after repeating the analysis in the hypertensive
population only (lower portion of Table 3).
|
Independent Predictors of Carotid IMT and Stiffness Index
Multiple regression analyses were performed to
assess independent predictors of carotid IMT and stiffness (Table 4). Age, BSA, and systolic blood
pressure were independent predictors of carotid IMT (multiple
R=0.54, P<0.0001), while total
cholesterol, smoking history, and sex did not enter the
model. Age, BSA, and male sex, but not cholesterol level,
smoking history, and systolic blood pressure, were independent
predictors of arterial stiffness (multiple
R=0.38, P<0.0001).
|
In the subset of hypertensive patients, age and BSA were independent
predictors of carotid IMT (multiple R=0.42,
P<0.01), and no residual correlation was found with
cholesterol levels (Figure 1). Similarly, Young’s elastic modulus
of the carotid was independently predicted by systolic blood
pressure and BSA, while the stiffness index was independently
positively correlated with age and smoking history and negatively with
cholesterol levels (Figure 2).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The present study indicates that mild to moderate hypercholesterolemia does not play a primary role in increasing common carotid artery IMT in otherwise-healthy hypertensive patients. In fact, although significant, positive, multivariate relationships were found between carotid structure and cholesterol levels after controlling for age and other potentially confounding parameters, hypertensive patients with normal and high cholesterol levels did not differ in carotid wall thickness, RWT, and cross-sectional area. In contrast, the association of hypertension with increased IMT was evident in both groups. Accordingly, independent predictors of carotid cross-sectional area included older age and higher BSA and systolic blood pressure but not total serum cholesterol (Table 4
). These data are partially in contrast with previous reports that indicated a role of hypercholesterolemia in inducing carotid intimal-medial thickening.12 19 40 41 42 43 44 However, 2 of these studies19 42 included hypercholesterolemic patients with mild or moderate hypertension; moreover, diabetic patients and/or subjects with signs or symptoms of cardiovascular disease were not excluded. Nevertheless, although Poli et al42 detected a significant increase in IMT in their hypercholesterolemic group, there was no significant correlation between carotid IMT and plasma cholesterol levels. In contrast, in the population described by Wendelhag et al,19 the distribution of IMT in hypercholesterolemic patients appeared to be similar to that in normocholesterolemic subjects except for a few subjects in whom IMT values suggested the inclusion of plaques in the calculation. In addition, studies conducted in normotensive children with familial hypercholesterolemia and very high cholesterol levels showed only modest associations between carotid IMT and cholesterol levels.43 44
Although it is unclear whether it is more clinically and prognostically meaningful to exclude from the calculation of IMT all discrete areas of wall thickening, measurements performed in arterial segments including discrete plaques could overemphasize the association between risk factors for atherosclerotic disease and the IMT of representative segments of the arterial tree. Data from our study suggest that when IMT is measured in areas free of discrete atherosclerotic lesions, common carotid wall thickness in hypertensive patients is not strongly affected by mild to moderate hypercholesterolemia. Moreover, our results are in accordance with experimental studies45 that suggest that intimal-medial thickening is mainly related to increased deformational arterial stresses due to blood pressure elevation, whereas hypercholesterolemia may be more influential in the genesis of discrete atherosclerotic plaques by focal deposition of lipids in the subintimal layers of the arterial wall. This concept is in agreement with observations that normotensive hypercholesterolemic children had mean wall thicknesses similar to those of normocholesterolemic controls, whereas the maximum IMT was significantly higher in the hypercholesterolemic group.43
A potential limitation of ultrasonographic evaluation of the arterial intimal-medial complex is that it does not allow separation of increased medial mass due to hypertrophy from increased intimal mass due to atherosclerosis and arteriosclerosis. Therefore, early atherosclerotic lesions involving only the intimal layer may cause only small increases in the composite wall thickness measured by vascular ultrasonography that might be confused with medial hypertrophy in the presence of hypertension. Although this could be a major limitation of ultrasonographic studies of preclinical atherosclerosis, the consistent ability of increased IMT to predict cardiovascular events in multiple populations11 12 13 14 15 suggests that the different processes that increase overall carotid wall thickness are all prognostically adverse. Furthermore, since the atherosclerotic process typically involves the arterial wall in a focal fashion, whereas hypertension induces diffuse thickening of the intimal-medial complex,46 ultrasonographic identification of focal intimal-medial thickening can be considered a reliable indicator of atherosclerosis per se.
Surprisingly, carotid stiffness, which is commonly considered an early indicator of vascular damage, was not increased by hypercholesterolemia. In fact, the stiffness index, which takes into account the nonlinearity of the pressure-diameter relation, and Young’s elastic modulus, which considers adaptive wall thickening, were not elevated in either hypertensive group, and in particular, were not increased in the hypercholesterolemic patients. Multiple regression analysis conducted in the whole population indicated that age, BSA, and sex, but not cholesterol levels, were independent predictors of the stiffness index. However, in a subanalysis of the hypertensive population, an unexpected modest but significant independent inverse relationship was found between stiffness index and cholesterol level. This surprising finding, which needs verification by other studies, confirms the lack of positive correlations between carotid stiffness and cholesterol levels after controlling for age and smoking history. Moreover, the augmentation index, which is related to aortic pulse wave velocity, was equally elevated in normocholesterolemic and hypercholesterolemic hypertensives, suggesting that neither carotid nor aortic compliance was substantially modified by mild-to-moderate hypercholesterolemia. The evidence for altered arterial stiffness in hypertensive patients when the pressure-sensitive augmentation index was used but not with the pressure-insensitive stiffness index is in accordance with previous reports that did not detect an impact of hypertension on arterial stiffness evaluated at a standardized pressure level.47 48 Although studies in hypercholesterolemic animals indicated increased arterial stiffness,20 21 results may have been affected by use of the pressure-dependent pulse wave velocity as the index of vascular stiffness. Other human observations did not detect reduced arterial compliance in nonfamilial hypercholesterolemia49 or an effect of high cholesterol levels on age-related increases in arterial stiffness.50 51 Moreover, a recent study reported a lack of association between aortic stiffening and extracoronary atherosclerotic disease, after controlling for the affect of age.52
Although ultrasonographic evaluation of uncomplicated hypertensive subjects allows the assessment of vascular damage in a preclinical phase of atherosclerotic disease, the lack of cholesterol-induced arterial modifications in our study may be due to selection of hypertensive subjects at relatively low risk. In fact, the prevalence of carotid plaques, although significantly higher than in normocholesterolemic subjects, was relatively low in the high-cholesterol hypertensive group (31%).
In conclusion, this study indicates that in patients with relatively mild, uncomplicated essential hypertension, sporadic hypercholesterolemia does not substantially affect carotid wall thickness or stiffness. However, although the relatively small sample size of this study had adequate power to detect a moderate intimal-medial thickening induced by high cholesterol levels, lesser changes might have gone undetected in our moderately sized population. Additionally, in the present study, the impact of hypercholesterolemia may have been overwhelmed by hypertension-induced arterial modifications. Further larger studies are needed to assess the independent effect of high cholesterol levels on arterial anatomy and stiffness in normotensive subjects.
|
Acknowledgments |
|---|
This study was supported in part by grants HL-18323 and HL-47540 from the National Heart, Lung, and Blood Institute, Bethesda, Md; the Michael Wolk Heart Foundation; and grant 97.04129.CT04 from Consiglio Nazionale delle Ricerche and grant ex-40% 1997 from MURST, Italy (to A.G.). P.S.S. has been the recipient of a research grant from Regione Autonoma della Sardegna, Italy.
Received December 15, 1998; accepted April 19, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Kannel WB, Neaton JD, Wentworth D, Thomas HE, Stamler J, Hulley SB, Kjelsberg MO. Overall and coronary heart disease mortality rates in relation to major risk factors in 325,348 men screened for the MRFIT Study. Am Heart J.. 1986;112:825–836.[Medline] [Order article via Infotrieve]
2. Kannel WB, Castelli WP, Gordon T, McNamara PM. Serum cholesterol, lipoproteins and the risk of coronary heart disease: the Framingham Study. Ann Intern Med.. 1971;74:1–12.
3.
Devereux RB, Alderman MH. Role of preclinical
cardiovascular disease in the evolution from risk
factor exposure to development of morbid events.
Circulation.. 1993;88:1444–1455.
4.
Hennerici M, Hulsbomer HM, Hefter H, Lammerts D,
Rautemberg W. Natural history of asymptomatic extracranial
arterial disease. Brain.. 1987;110:777–791.
5.
Craven TE, Ryu JE, Espeland MA, Kahl FR, McKinney WM,
Toole JF, McMahan MR, Thompson CJ, Heiss G, Crouse JR III. Evaluation
of the associations between carotid artery
atherosclerosis and coronary artery
stenosis: a case-control study. Circulation.. 1990;82:1230–1242.
6.
Giral P, Pithois-Merli I, Filitti V, Levenson J,
Plainfosse MC, Mainardi C, Simon AC. Risk factors and early
extracoronary atherosclerotic plaques detected by three-site
ultrasound imaging in hypercholesterolemic men.
Arch Intern Med.. 1991;151:950–956.
7.
Suurküla M, Agewall S, Fagenberg B, Wendelhag I,
Widgren B, Wikstrand J. Ultrasound evaluation of atherosclerotic
manifestations in the carotid artery in high-risk hypertensive
patients. Arterioscler Thromb.. 1994;14:1297–1304.
8. Young W, Gofman JW, Tandy R, Malamud N, Waters ESG. The quantification of atherosclerosis, III: the extent of correlation of degrees of atherosclerosis within and between the coronary and cerebral vascular beds. Am J Cardiol.. 1960;6:300–308.
9. Mitchell JRA, Schwartz CJ. Relationship between arterial disease in different sites: a study of the aorta and coronary, carotid and iliac arteries. BMJ. 1962;1:1293–1301.
10.
Geroulakos G, O’Gorman DJ, Kalodiki E, Sheridan DJ,
Nicolaides AN. The carotid intima-media thickness as a marker of severe
symptomatic coronary artery disease. Eur
Heart J.. 1994;15:781–785.
11.
Burke GL, Evans GW, Riley WA, Sharrett AR, Howard G,
Barnes RW, Rosamond W, Crow RS, Rautaharju PM, Heiss G.
Arterial wall thickness is associated with prevalent
cardiovascular disease in middle-aged adults: the
Atherosclerosis Risk in Communities (ARIC) Study.
Stroke.. 1995;26:386–391.
12. Salonen JT, Salonen R. Arterial wall thickness, carotid atherosclerosis and the risk of myocardial infarction and cerebrovascular stroke. In: Touboul PJ, Crouse JR, eds. Intima-Media Thickness and Atherosclerosis. New York, NY: Parthenon Publishing Group; 1997.
13.
Kuller LH, Shemanski L, Psaty BM, Borhani NO, Gardin J,
Haan MN, O’Leary DH, Savage PJ, Tell GS, Tracy R. Subclinical disease
as an independent risk factor for cardiovascular
disease. Circulation.. 1995;92:720–726.
14.
O’Leary DH, Polak JF, Kronmal RA, Kittner SJ, Bond MG,
Wolfson SK Jr, Bommer W, Price TR, Gardin JM, Savage PJ. Distribution
and correlates of sonographically detected carotid artery disease in
the Cardiovascular Health Study. Stroke.. 1992;23:1752–1760.
15.
Belcaro G, Nicolaides AN, Laurora G, Cesarone MR, De
Sanctis M, Incandela L, Barsotti A. Ultrasound morphology
classification of the arterial wall and
cardiovascular events in a 6-year follow-up study.
Arterioscler Thromb Vasc Biol.. 1996;16:851–856.
16.
Roman MJ, Saba PS, Pini R, Spitzer M, Pickering TG,
Rosen S, Alderman MH, Devereux RB. Parallel cardiac and vascular
adaptation in hypertension. Circulation.. 1992;86:1909–1918.
17.
Lemne C, Jogestrand T, deFaire U. Carotid intima-media
thickness and plaque in borderline hypertension. Stroke.. 1995;26:34–39.
18. Poli A, Tremoli E, Colombo A, Sirtori M, Pignoli P, Paoletti R. Ultrasonographic measurement of the common carotid artery wall thickness in hypercholesterolemic patients: a new model for the quantitation and follow-up of preclinical atherosclerosis in living human subjects. Atherosclerosis.. 1988;70:253–261.[Medline] [Order article via Infotrieve]
19.
Wendelhag I, Wiklund O, Wikstrand J.
Arterial wall thickness in familial
hypercholesterolemia: ultrasound measurement of
intima-media thickness in the common carotid artery. Arterioscler
Thromb.. 1992;12:70–77.
20.
Burattini R, Montanari L, Mulligan LJ, Cannon MS, Gross
DR. Evaluation of hypercholesterol diet-induced changes in
viscoelastic properties of carotid circulation in pigs. Am J
Physiol.. 1992;263:H1919–H1926.
21.
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.
22. Yaginuma T, Cohn JN. Introduction to wave reflection, wave travel and changes with modification of geometric and physical parameters. J Hypertens. 1992;10(suppl):S71–S72.
23. Working Group on Management of Patients with Hypertension and High Blood Cholesterol. National Education Programs Working Group report on the management of patients with hypertension and high blood cholesterol. Ann Intern Med.. 1991;114:224–237.
24.
Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R.
Intimal plus medial thickness of the arterial wall: a
direct measurement with ultrasound imaging. Circulation.. 1986;74:1399–1406.
25.
Roman MJ, Pickering TG, Pini R, Schwartz JE, Devereux
RB. Prevalence and determinants of cardiac and vascular
hypertrophy in hypertension. Hypertension.. 1995;26:369–373.
26. Roman MJ, Pini R, Pickering TG, Devereux RB. Noninvasive measurement of arterial compliance in hypertensive compared with normotensive adults. J Hypertens. 1992;10(suppl 6):S115–S118.
27. Saba PS, Roman MJ, Pini R, Spitzer M, Ganau A, Devereux RB. Relation of pressure waveform to left ventricular and carotid anatomy in normotensive subjects. J Am Coll Cardiol.. 1993;22:1873–1880.[Abstract]
28. Saba PS, Scorzoni D, Cavallini C, Longhini C, Pini R, Ganau A. Arterial tonometry: principles and clinical applications in hypertension. High Blood Press.. 1996;5:241–250.
29. Hamilton WF, Dow P. An experimental study of the standing waves in the pulse propagated through the aorta. Am J Physiol. 1939;125:48–59.
30. Schnabel TG Jr, Fitzpatrick HF, Peterson LH, Rashkind WJ, Talley D, Raphael RL. A technic of vascular catheterization with small plastic catheters: its utilization to measure the arterial pulse wave velocity in man. Circulation. 1952;5:257–262.[Medline] [Order article via Infotrieve]
31.
Kroeker EJ, Wood EH. Comparison of
simultaneously recorded central and
peripheral arterial pressure pulses during
rest, exercise and tilted position in man. Circ Res.. 1955;3:623–632.
32.
O’Rourke MF. Arterial stiffness,
systolic blood pressure and logical treatment of
arterial hypertension. Hypertension. 1990;15:339–347.
33. 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]
34.
Hirai T, Sasayama S, Kawasaki T, Yagi SI. Stiffness of
systemic arteries in patients with myocardial infarction: a noninvasive
method to predict severity of coronary
atherosclerosis. Circulation. 1989;80:78–86.
35.
Kelly R, Daley J, Avolio A, O’Rourke M.
Arterial dilation and reduced wave reflection: benefit of
dilevalol in hypertension. Hypertension.. 1989;14:14–21.
36.
Murgo JP, Westerhof N, Giolma JP, Altobelli SA. Aortic
input impedance in normal man: relationship to pressure wave forms.
Circulation.. 1980;62:105–116.
37. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem.. 1972;18:499–502.[Abstract]
38.
O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke
GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk
factor for myocardial infarction and stroke in older adults:
Cardiovascular Health Study Collaborative Research
Group. N Engl J Med.. 1999;340:14–22.
39.
Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu
C-r, Liu C-h, Azen SP. The role of carotid arterial
intima-media thickness in predicting clinical coronary events.
Ann Intern Med.. 1998;128:262–269.
40.
Crouse JR, Toole JF, McKinney WM, Dignan MB, Howard G,
Kahl FR, McMahan MR, Harpold GH. Risk factors for extracranial carotid
artery atherosclerosis. Stroke.. 1987;18:990–996.
41.
Handa N, Matsumoto M, Maeda H, Hougaku H, Ogawa S,
Fukunaga R, Yoneda S, Kimura K, Kamada T. Ultrasonic evaluation of
early carotid atherosclerosis. Stroke.. 1990;21:1567–1572.
42. Poli A, Tremoli E, Colombo A, Sirtori M, Pignoli P, Paoletti R. Ultrasonographic measurement of the common carotid artery wall thickness in hypercholesterolemic patients: a new model for the quantitation and follow-up of preclinical atherosclerosis in living human subjects. Atherosclerosis.. 1988;70:253–261.
43.
Pauciullo P, Iannuzzi A, Sartorio R, Irace C, Covetti
G, Di Costanzo A, Rubba P. Increased intima-media thickness of the
common carotid artery in hypercholesterolemic children.
Arterioscler Thromb.. 1994;14:1075–1079.
44.
Tonstad S, Joakimsen O, Stensland-Bugge E, Leren TP,
Ose L, Russel D, Bønaa KH. Risk factors related to carotid
intima-media thickness and plaque in children with familial
hypercholesterolemia and control subjects.
Arterioscler Thromb Vasc Biol.. 1996;16:984–991.
45.
Dobrin PB. Mechanical factors associated with the
development of intimal and medial thickening in vein grafts subjected
to arterial pressure: a model of arteries exposed to
hypertension. Hypertension.. 1995;26:38–43.
46.
Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W,
Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW. A
definition of initial, fatty streak, and intermediate lesions of
atherosclerosis: a report from the Committee on
Vascular Lesions of the Council on
Arteriosclerosis, American Heart Association.
Circulation.. 1994;89:2462–2478.
47. Devereux RB, Waeber B, Roman MJ. Conclusions on the measurement of arterial wall thickness: anatomic, physiologic and methodologic considerations. J Hypertens. 1992;10(suppl 6):S119–S121.
48.
Laurent S, Caviezel B, Beck L, Girerd X, Billaud E,
Boutouyrie P, Hoeks A, Safar M. Carotid artery distensibility and
distending pressure in hypertensive humans. Hypertension.. 1994;23:878–883.
49. Giannattasio C, Mangoni AA, Carugo S, Bombelli M, Stefanoni P, Failla M, Stella ML, Sega R, Grassi G, Vergani C, Mancia G. Arterial compliance in familial hypercholesterolemia: a preliminary report. J Hypertens. 1993;11(suppl 5):S82–S83.
50. Dart AM, Lacombe F, Yeoh JK, Cameron JD, Jennings GL, Laufer E, Esmore DS. Aortic distensibility in patients with isolated hypercholesterolemia, coronary artery disease, or cardiac transplant. Lancet.. 1991;338:270–273.[Medline] [Order article via Infotrieve]
51. O’Rourke MF, Avolio AP, Clyde K, Simons L, Ho K, Bains D. High serum cholesterol and atherosclerosis do not contribute to increased arterial stiffening with age. J Am Coll Cardiol. 1986;7(suppl A):247A. Abstract.
52. Megnen JL, Simon A, Denarie N, Del Pino M, Gariepy J, Segond P, Levenson J. Aortic stiffening does not predict coronary and extracoronary atherosclerosis in asymptomatic men at risk from cardiovascular disease. Am J Hypertens.. 1998;11:293–301.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  B. Williams, P. S. Lacy, J. K. Cruickshank, D. Collier, A. D. Hughes, A. Stanton, S. Thom, H. Thurston, and for the CAFE and ASCOT Investigators Impact of Statin Therapy on Central Aortic Pressures and Hemodynamics: Principal Results of the Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) Study Circulation, January 6, 2009; 119(1): 53 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Magyar, G. Paragh, E. Katona, A. Valikovics, I. Seres, L. Csiba, and D. Bereczki Serum Cholesterols Have a More Important Role Than Triglycerides in Determining Intima-Media Thickness of the Common Carotid Artery in Subjects Younger Than 55 Years of Age J. Ultrasound Med., September 1, 2004; 23(9): 1161 - 1169. [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]
|
|
|
|
 |
|
 D. Liao, T. Y. Wong, R. Klein, D. Jones, L. Hubbard, and A. R. Sharrett Relationship Between Carotid Artery Stiffness and Retinal Arteriolar Narrowing in Healthy Middle-Aged Persons Stroke, April 1, 2004; 35(4): 837 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. ZUREIK, A. BENETOS, C. NEUKIRCH, D. COURBON, K. BEAN, F. THOMAS, and P. DUCIMETIERE Reduced Pulmonary Function Is Associated with Central Arterial Stiffness in Men Am. J. Respir. Crit. Care Med., December 15, 2001; 164(12): 2181 - 2185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sun, K. M. Dwyer, C. N. B. Merz, W. Sun, C. A. Johnson, A. M. Shircore, and J. H. Dwyer Blood Pressure, LDL Cholesterol, and Intima-Media Thickness : A Test of the "Response to Injury" Hypothesis of Atherosclerosis Arterioscler Thromb Vasc Biol, August 1, 2000; 20(8): 2005 - 2010. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||