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1 Departments of Clinical Physiology, 2 Pediatrics, 3 Clinical Chemistry, and 4 Medicine and 5 Turku Centre for Positron Emission Tomography and 6 Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, FIN-20520 Turku, Finland
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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To characterize brachial artery flow-mediated dilatation (FMD) in children, we monitored arterial diameter changes with ultrasound between 40 and 180 s after a 4.5-min forearm cuff occlusion-induced hyperemia in 105 healthy children (mean age, 11 yr; range, 9-16 yr). The peak FMD was 7.7 ± 4.0% and occurred 79 ± 33 s after cuff release. FMD at 60 s (5.3 ± 4.0%) was significantly lower than the peak FMD (P < 0.0001). Twenty-three percent of the children (n = 24) reached peak FMD first after 110 s of postocclusion. Compared with others, these late responders weighed less, had smaller vessel size, and were more often girls, but had similar peak FMD. In multivariate analysis, FMD responses were inversely associated with brachial artery baseline diameter and serum cholesterol concentration. We conclude that the time to reach the peak FMD response in children varies considerably. When studying endothelial function in children with the use of the noninvasive ultrasound method, several brachial artery diameter measurements up to 120 s after cuff release are needed to determine the true FMD peak response.
atherosclerosis; ultrasound; endothelium; cholesterol
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THE ATHEROSCLEROTIC PROCESS begins in childhood and develops gradually for decades before clinical symptoms arise (19). This provides a window for identification of high-risk individuals already in the subclinical stages of the atherosclerotic disease. The earliest stages of the atherosclerotic process are characterized by impairment of arterial endothelial function (19). The integrity of endothelial vasoreactivity can be noninvasively assessed by measuring flow-mediated dilatation (FMD) of conduit arteries with high-resolution ultrasound (5). The brachial artery dilatation response to increased shear stress is mainly due to endothelial release of nitric oxide (13) and correlates with coronary endothelial function (2). With the use of this method, endothelial dysfunction has been documented already in children and adolescents at high risk for atherosclerotic diseases (5, 7, 9, 15, 21).
Despite increasing use of this noninvasive imaging technique as an intermediate endpoint in interventional risk factor modification and followup studies already in pediatric subjects (15), the methodological aspects have received relatively little attention. There is increasing need for further study of the methodology as well as for the standardization of methods employed to study vascular changes in children to enhance measurement reliability and reproducibility and to improve comparability among studies. Although not recommended for routine clinical use, the potential value of the noninvasive ultrasound test as a clinical tool to help in decision making about the initiation of pharmacological primary prevention therapies and for early identification and management of asymptomatic high-risk subjects has been discussed (17, 23). This study was undertaken gain insight on the temporal nature of the brachial artery vasodilatation response to endothelium-dependent and -independent stimuli in healthy children and adolescents for methodological standardization purposes.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects
We studied 105 children (mean age, 10 yr; range, 9-16 yr; 59 boys) who either participated a study aiming at decreasing children's exposure to known environmental atherosclerotic risk factors (16) or were children of Turku University staff members. All subjects were nonsmokers and without any regular medication. The characteristics of the subjects are shown in Table 1. The study was conducted according to the Declaration of Helsinki, and the study protocol had been approved by the Joint Commission on Ethics of the Turku University and the Turku University Central Hospital. Written informed consent was acquired from the legal guardians of the children, and they were also encouraged to get an approval from the child.
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Ultrasound Studies
All studies were performed by an experienced vascular sonographer using an Acuson Sequoia 512 mainframe (Acuson; Mountain View, CA) with a 13.0-MHz linear array transducer. The studies were done in the morning to fasting patients between 7:30 and 9:00 AM. To minimize external stimuli, all studies were carried out in silence in a clinical research laboratory room. Blood pressure was measured from the nondominant arm using a sphygmomanometer three times during the study.Brachial artery physiology. Brachial artery diameter was measured from B-mode ultrasound images. In all studies, scans were obtained at rest and during reactive hyperemia. The subjects laid quietly for 10 min before the first scan. The brachial artery was scanned in longitudinal section 5-15 cm above the elbow. Depth and gain settings were set to optimize images of the lumen/arterial wall interface, and the operating parameters were not changed during the study. When a satisfactory transducer position was found, the position was marked on the skin and the arm remained in the same position throughout the study. All ultrasound scans were recorded on super-VHS tapes for off-line analysis. A resting scan was performed, and arterial flow velocity was measured using a Doppler signal. Increased flow was then induced by inflation of an adult-size (12 × 44.5 cm) pneumatic tourniquet placed around the forearm (distal to the scanned part of the artery) to a pressure of 250 mmHg for 4.5 min, followed by release. We use an adult-size cuff in children, because in our experience the use of a narrower pediatric cuff often causes discomfort in pediatric patients. Subsequent scans were taken continuously between 40 and 180 s after cuff deflation. We also included a repeated flow velocity recording for the first 15 s after the cuff was released. Because a shift in brachial artery position frequently occurs when the cuff is released, great care was taken to find and image the largest lumen diameter (the center of the artery) during the measurement interval between 40 and 180 s of postocclusion.
Vessel diameter was measured by an experienced reader blinded to the study subjects' laboratory data. The arterial diameter was measured at a fixed distance from an anatomic marker (e.g., a fascial plane) using ultrasonic calipers. Measurements were taken from the anterior to the posterior "m" line (5) at end diastole, incident with the R-wave on a continuously recorded electrocardiogram every 10 s between 40 and 120 s after cuff deflation and every 15 s from 120 to 180 s of postocclusion (including a total of 13 measurements). The first posthyperemia scan was taken at 40 s because it was the earliest time point practicable because flow velocity was recorded for the first 15 s after the cuff release. The maximal proportional dilatation from baseline (FMD, in %) and the total dilatation response, defined as the area under the FMD vs. time curve during the 40- to 180-s period after hyperemia (AUC, in % · s), were assessed. Nitrate-mediated endothelium-independent dilatation (NMD) capacity was tested by administering four consecutive sublingual 50-µg doses of glyceryltrinitrate (GTN), all 5 min apart (cumulative dose, 200 µg). Brachial artery diameter was measured 5 min after each dose to acquire a dose-response curve. Maximum diameter 5 min after maximum cumulative nitrate administration was also used to calculate the proportional increase in diameter from the baseline value. The methods described above have been previously shown to be accurate and reproducible for measurement of small changes in arterial diameter (12, 22). In our laboratory, the between-observer reliability of the brachial artery baseline diameter and FMD measurements have recently been found to be excellent, with intraclass correlation coefficients being 0.998 and 0.964, respectively (12).Serum Lipoproteins
Venous blood samples were taken in the morning, after an overnight fast (10-12 h). Serum total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and triglyceride concentrations were measured using standard enzymatic methods (Boehringer-Mannheim) with a fully automated analyzer (model 917, Hitachi; Tokyo, Japan). The low-density lipoprotein-cholesterol (LDL-C) concentration was calculated using Friedewald's equation (10).Statistical Methods
Results are expressed as means ± SD unless stated otherwise. Univariate associations between the study variables were analyzed by calculating the Pearson's correlation coefficients (r). The correlates of arterial dilatation responses were studied by multivariate analyses using the linear regression technique. The following explanatory variables were included in the analysis: age, gender, body mass index (BMI), blood pressure, total cholesterol or LDL-C, HDL-C, and brachial baseline diameter. All statistical analyses were performed using a statistical analysis system (SAS Institute; Cary, NC) (20).| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The mean brachial artery diameter was 3.1 ± 0.3 mm, and the
mean peak endothelium-dependent dilatation was 7.7 ± 4.0% (Table 1). The development of the brachial artery dilatation response between
40 and 180 s after occlusion-induced induced hyperemia is shown in
Fig. 1. The highest mean dilatation
(5.5 ± 3.9%) occurred at 70 s after cuff deflation, but all
mean values between 40 and 180 s of postocclusion exceeded the
baseline values by >3%. The average time to the true peak
dilatation was 79 ± 33 s (median, 70 s) after cuff
release. The time to the peak dilatation response did not correlate
with the peak response (r = 0.03, P = 0.79). The peak dilatation response was greater than dilatation at
70 s of postocclusion (7.7 ± 4.0 vs. 5.3 ± 4.0%,
P < 0.0001). By 120 s of postocclusion, >90% of
the subjects had reached their peak response (Fig.
2). Had we used the traditional
measurement window of 40-60 s after the cuff deflation, 58% of
all peak FMD responses would have gone undetected (Table
2).
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A substantial proportion of the children reached their peak FMD
response in the second half of the measurement window (after 110 s
of postocclusion), indicating that many children reach the peak FMD
response rather late. The late responders, arbitrarily defined as
children having a greater AUC between 110 and 180 s of
postocclusion (AUC 110-180) than the AUC between 40 and 110 s
of postocclusion (AUC 40-110), differed clearly from the early responders (Table 3). The late responders
(n = 24, 23%) weighed less and had a smaller brachial
luminal diameter and lower baseline flow compared with the early
responders. Gender distributions of the groups also differed, because
the late responders were more often girls, but the peak FMD (Table 3)
and serum lipid levels (data not shown) in the two groups were closely
similar. Figure 3 shows the development
of the FMD response in these two groups.
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The mean maximum NMD of the study children was 11.5 ± 4.5%, in practice a dilatation value similar to the dilatation observed after administration of the final dose (cumulative dose, 200 µg) of GTN (11.1 ± 4.6, P = 0.55), suggesting that a plateau dilatation had not been achieved.
The univariate correlations of FMD and NMD with relevant physiological
parameters are shown in Table 4. Peak FMD
associated inversely with the brachial artery diameter
(r = 
0.32, P < 0.001) but was not
correlated with the relative increase in blood flow during hyperemia
(increase in the flow velocity × time interval) (r = 0.11, P = 0.29). The FMD values associated inversely
with LDL-C and total cholesterol concentrations (Table 4). In the multivariate regression model, the only significant explanatory variables for FMD responses were the brachial artery baseline diameter
and serum total cholesterol concentration (Table
5).
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NMD was inversely associated with the brachial artery diameter
(r = 0.32, P < 0.001), BMI
(r = 0.28, P = 0.007), and serum total cholesterol (r = 0.23, P = 0.03) (Table 4). The association between NMD and serum cholesterol
concentration also remained significant after adjustment for sex, BMI,
and vessel size (P = 0.05).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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This study characterizes features of the brachial artery dilatation response after occlusion-induced hyperemia in children and adolescents and therefore has important implications in the study of arterial properties in this age group. Because arterial vasoreactivity is increasingly used as an intermediate endpoint in risk factor modification studies, the methodology should be meticulously depicted and standardized. Previous studies have documented that exposure of children to environmental risk-increasing factors such as dyslipidemia and diabetes (5, 7, 9, 11, 14, 15, 21) or atheroprotective risk factor modification, e.g., antioxidant therapy (15), can alter arterial vasoreactivity. In line with these earlier observations, FMD associated inversely with serum total cholesterol and LDL-C in the present study, and the associations were also seen in the multivariate regression model. These data thus show that serum cholesterol concentration influences endothelial physiology in healthy children and adolescents.
The use of brachial artery FMD as a measure of systemic endothelial function has been well characterized, with comparisons of baseline diameter and hyperemic diameter acquired at 45-60 s after ischemia, expressed as a percent increase in baseline diameter (5). Our results, however, imply that the time needed to achieve maximal hyperemia-induced vasodilatation varies a great deal between study subjects, and diameter measurements should, therefore, be taken during a longer time interval after hyperemia. If endothelial function is defined as the percent increase in luminal diameter at 60-s postocclusion, only a small proportion of true peak responses will be recorded. In the present study, peak FMD would have gone undetected in 58% of all children studied if the commonly used measurement window between 40 and 60 s of postocclusion was used. Therefore, a large proportion of previous studies have underestimated the peak FMD, because vessel diameter has only been measured at one early time point after hyperemia. Previous small-scale studies in adults have suggested that the average FMD peaks at 60 s after cuff deflation, but the mean time to reach the true peak dilatation response may be as long as 81 s (4). In a recent study, Berry and co-workers (3) reported that peak endothelium-dependent dilatation after hyperemia in adults is detected on average at 71-s postocclusion when using an upper arm cuff placement and already at 49 s when using a forearm cuff similar to the present study. Our findings show that most children reach peak dilatation between 40 and 120 s after cuff release (Table 2) and that the average time of peak dilatation is 79 s after cuff deflation and, i.e., much later than in the adult subjects (3). In our study, the mean FMD in children was greatest at 70 s of postocclusion. Our current finding that the true peak response may even be over 2 percent units higher than the response at 60-s postocclusion is in line with the findings of Bressler et al. (4). It has been suggested that the sufficient change in FMD for definite conclusions in intervention trials would be as low as 2 percent units (22). Therefore, our results emphasize the importance of using several time points for measurement of FMD in each study participant, because the true peak dilatation response often differs by >2 percent units from the response measured at any other single time point during the induced hyperemia. It has also been proposed that serial measurements of vessel diameter ranging from 30 to 90 s of postocclusion should be used (3), and, according to the current results, the time point of the last diameter measurement should not be earlier than at 2 min after cuff release. Holding the ultrasound probe for up to 3 min after cuff release, however, increases the risk of shift in the brachial artery image, so that the scanned vessel diameters may change due to "off-center" imaging. Therefore, great care needs to be taken to maintain the probe position throughout the imaging interval by finding a relaxed position for the hand holding the transducer and by using anatomic markers.
We measured brachial artery diameter from 40 to 180 s of postocclusion mainly due to the assumption that the high majority of peak FMD responses would be observed after 40 s of postocclusion. It might, however, be preferable to take the first postocclusion diameter measurements already at 20-30 s after cuff deflation. The Doppler measurement of increased blood flow velocity during the first 15 s after cuff release has hampered diameter measurements during the first 30 s of hyperemic flow. In light of our results there is, however, no justified reason why the increase in blood flow during the endothelial test should be assessed because there is no relationship between the increase in blood flow velocity and FMD.
Interestingly, a small group of children differed from the majority by having a remarkably late dilatation response (the late responders, n = 24). Features of these children also differed from the others but, nevertheless, the peak FMD values in the two groups were closely similar (Table 3). As our understanding of this noninvasive technique for studying the integrity of physiological endothelial function increases, variables such as the time to the peak dilatation may turn out to be informative, in addition to the extent of vasodilatation per se.
Smooth muscle-dependent NMD has been used as a control test for the FMD test to ensure that the decreased FMD capacity observed in the test is truly a consequence of endothelial dysfunction, not a reflection of underlying smooth muscle dysfunction (5). It seems, however, that vascular wall smooth muscle relaxation attenuates when the atherosclerotic processes progress (1, 18), but the changes become evident rather late in the process and are usually preceded by endothelial dysfunction. Therefore, it may be futile to measure smooth muscle function in addition to FMD, because it no longer can be considered a valid control for the endothelium dependency of impaired vasoreactivity. The measurement of smooth muscle function may, however, be warranted in the study of the atherosclerotic process and when vasoreactivity in patients on long-acting nitrate medication is being followed up.
Former studies assessing endothelium-independent smooth muscle function in children have used GTN doses of 400 µg, which correspond to antianginal doses used in clinical practice (5). The use of large GTN doses has, however, resulted in adverse effects such as headache in a large proportion of children studied. Therefore, we used four consecutively administered doses of sublingual GTN to avoid discomfort and side effects and to acquire a dose-response curve (Fig. 1). The cumulative dose of 200 µg (administered in 15 min) failed to induce a plateau response in the children studied, because maximal NMD correlated inversely with weight, and the dilatation response increased with every consecutive dose of GTN. None of the children studied, however, experienced side effects such as headache, dizziness, or decreased blood pressure, and the maximal NMD was significantly higher than the peak FMD. In light of previous results it may not be necessary to administer doses great enough to achieve the plateau response, because in adults the plateau responses of coronary patients and healthy controls are in fact similar, and the differences in NMD are only evident in submaximal doses (18). It may be plausible to use consecutive administrations of GTN in small doses when studying smooth muscle-dependent vasoreactivity in children. If the response plateau has to be reached, a cumulative dose exceeding 200 µg should be used. Previous studies (6, 8, 9, 21) in healthy adolescents without cardiovascular risk factors have reported plateau NMD responses as high as 12.4-21%.
In summary, the time to reach the peak FMD response varies considerably in healthy children and adolescents, and therefore when studying endothelial function in children using the noninvasive ultrasound method, several brachial artery diameter measurements up to 120 s after cuff release are needed to determine the true FMD peak response.
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ACKNOWLEDGEMENTS |
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The authors thank Mia Laakkonen and Tuula Laukkanen for skillful technical assistance and Pohl-Boskamp for providing the nitroglycerin preparation used in this study.
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FOOTNOTES |
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This study was financially supported by the Finnish Medical Foundation, the Medical Society Duodecim in Turku, the Research Foundation of Orion Corporation, the Lydia Maria Julin Foundation, the Wäinö Edward Miettinen Foundation, the Turku University Foundation, the Academy of Finland, the Juho Vainio Foundation, the Finnish Foundation of Cardiovascular Research, the Foundation for Pediatric Research, and the Signe and Arne Gyllenberg Foundation.
Address for reprint requests and other correspondence: M. J. Järvisalo, Centre of Applied and Preventive Cardiovascular Medicine, Kiinamyllynkatu 10, FIN-20520 Turku, Finland (E-mail: mikko.jarvisalo{at}utu.fi).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 12 July 2001; accepted in final form 20 September 2001.
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REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Adams, MR,
Robinson J,
McCredie R,
Seale JP,
Sorensen KE,
Deanfield JE,
and
Celermajer DS.
Smooth muscle dysfunction occurs independently of impaired endothelium- dependent dilation in adults at risk of atherosclerosis.
J Am Coll Cardiol
32:
123-127,
1998
2.
Anderson, TJ,
Uehata A,
Gerhard MD,
Meredith IT,
Knab S,
Delagrange D,
Lieberman EH,
Ganz P,
Creager MA,
and
Yeung AC.
Close relation of endothelial function in the human coronary and peripheral circulations.
J Am Coll Cardiol
26:
1235-1241,
1995[Abstract].
3.
Berry, KL,
Skyrme-Jones RA,
and
Meredith IT.
Occlusion cuff position is an important determinant of the time course and magnitude of human brachial artery flow-mediated dilation.
Clin Sci (Colch)
99:
261-267,
2000[Medline].
4.
Bressler, B,
Chan S,
and
Mancini GB.
Temporal response of brachial artery dilation after occlusion and nitroglycerin.
Am J Cardiol
85:
396-400,
2000[ISI][Medline].
5.
Celermajer, DS,
Sorensen KE,
Gooch VM,
Spiegelhalter DJ,
Miller OI,
Sullivan ID,
Lloyd JK,
and
Deanfield JE.
Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.
Lancet
340:
1111-1115,
1992[ISI][Medline].
6.
Celermajer, DS,
Sorensen K,
Ryalls M,
Robinson J,
Thomas O,
Leonard JV,
and
Deanfield JE.
Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents.
J Am Coll Cardiol
22:
854-858,
1993[Abstract].
7.
Clarkson, P,
Celermajer DS,
Donald AE,
Sampson M,
Sorensen KE,
Adams M,
Yue DK,
Betteridge DJ,
and
Deanfield JE.
Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels.
J Am Coll Cardiol
28:
573-579,
1996[Abstract].
8.
Clarkson, P,
Celermajer DS,
Powe AJ,
Donald AE,
Henry RM,
and
Deanfield JE.
Endothelium-dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease.
Circulation
96:
3378-3383,
1997
9.
Donaghue, KC,
Robinson J,
McCredie R,
Fung A,
Silink M,
and
Celermajer DS.
Large vessel dysfunction in diabetic adolescents and its relationship to small vessel complications.
J Pediatr Endocrinol Metab
10:
593-598,
1997[ISI][Medline].
10.
Friedewald, WT,
Levy RI,
and
Fredrickson DS.
Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
Clin Chem
18:
499-502,
1972[Abstract].
11.
Jarvisalo, MJ.
Endothelial function is impaired in children with type 1 diabetes (Abstract).
Circulation
102, Suppl II:
326,
2000
12.
Jarvisalo, MJ,
Jartti L,
Toikka JO,
Hartiala JJ,
Ronnemaa T,
and
Raitakari OT.
Noninvasive assessment of brachial artery endothelial function with digital ultrasound and 13-MHz scanning frequency: feasibility of measuring the true inner luminal diameter using the intima-lumen interface.
Ultrasound Med Biol
26:
1257-1260,
2000[ISI][Medline].
13.
Joannides, R,
Haefeli WE,
Linder L,
Richard V,
Bakkali EH,
Thuillez C,
and
Luscher TF.
Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo.
Circulation
91:
1314-1319,
1995
14.
Leeson, CP,
Kattenhorn M,
Morley R,
Lucas A,
and
Deanfield JE.
Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life.
Circulation
103:
1264-1268,
2001
15.
Mietus-Snyder, M,
and
Malloy MJ.
Endothelial dysfunction occurs in children with two genetic hyperlipidemias: improvement with antioxidant vitamin therapy.
J Pediatr
133:
35-40,
1998[ISI][Medline].
16.
Niinikoski, H,
Viikari J,
Ronnemaa T,
Lapinleimu H,
Jokinen E,
Salo P,
Seppanen R,
Leino A,
Tuominen J,
Valimaki I,
and
Simell O.
Prospective randomized trial of low-saturated-fat, low-cholesterol diet during the first 3 years of life. The STRIP baby project.
Circulation
94:
1386-1393,
1996
17.
Raitakari, OT,
and
Celermajer DS.
Flow-mediated dilatation.
Br J Clin Pharmacol
50:
397-404,
2000[ISI][Medline].
18.
Raitakari, OT,
Seale JP,
and
Celermajer DS.
Impaired vascular responses to nitroglycerin in subjects with coronary atherosclerosis.
Am J Cardiol
87:
217-219,
2001[ISI][Medline].
19.
Ross, R.
The pathogenesis of atherosclerosis-an update.
N Engl J Med
314:
488-500,
1986[ISI][Medline].
20.
SAS Institute.
SAS User's Guide/STAT. Cary, NC: SAS Institute, 1998.
21.
Sorensen, KE,
Celermajer DS,
Georgakopoulos D,
Hatcher G,
Betteridge DJ,
and
Deanfield JE.
Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level.
J Clin Invest
93:
50-55,
1994.
22.
Sorensen, KE,
Celermajer DS,
Spiegelhalter DJ,
Georgakopoulos D,
Robinson J,
Thomas O,
and
Deanfield JE.
Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility.
Br Heart J
74:
247-253,
1995
23.
Tonstad, S.
Role of lipid-lowering pharmacotherapy in children.
Paediatr Drugs
2:
11-22,
2000[Medline].
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) and late responders
(
). Children who had a greater area under the
flow-mediated dilatation vs. time curve (AUC) between 110 and 180 s of postocclusion (AUC 110-180) than between 40 and 110 s of
postocclusion (AUC 40-110) were defined to be late responders
(n = 24), whereas the other children were regarded as
early responders (n = 81).