(Stroke. 1999;30:1572-1576.)
© 1999 American Heart Association, Inc.
Original Contributions |
From the Departments of Clinical Physiology (K.J.-U.) and Cardiology (M.J.-U.) and the Research Center of General Medicine (J.J.), Karolinska Hospital, Stockholm, Sweden.
Correspondence to Dr Kerstin Jensen-Urstad, Department of Clinical Physiology, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail Kerstin.Jensen-Urstad{at}kirurgi.ki.se
| Abstract |
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MethodsCCA diameter and IM thickness of the distal right and left CCAs were measured by high-frequency ultrasound methods. Fifty-seven men (73% of the invited men) and 47 women (62% of the invited women) participated.
ResultsIn the whole group the CCA diameter was correlated with gender (P<0.001), cholesterol (P=0.007), triglycerides (P<0.001), apoB (P<0.001), apoB/A-1 (P<0.001), systolic blood pressure (P=0.001), and glucose (P=0.006). HDL was inversely correlated with mean CCA diameter (P=0.003). In men the CCA diameter was correlated with a combined risk factor score (P=0.005), systolic blood pressure (P=0.011), platelet count (P=0.033), apoB (P=0.025), and occurrence of plaque (P=0.003). In women the CCA diameter was correlated with a combined risk factor score (P=0.010), systolic blood pressure (P=0.033), body mass index (P<0.001), cholesterol (P=0.009), triglycerides (P=0.14), apoB (P=0.002), and apoB/A1 (P=0.003). IM thickness was correlated with systolic blood pressure (P<0.001).
ConclusionsThere are correlations between risk factors for cardiovascular disease and carotid artery diameter and IM thickness in both women and men in a population of 55-year-old subjects. The increased vessel diameter in subjects with cardiovascular risk factors may be a sign of attenuated vasoregulation, which could be an important factor during the development of atherosclerosis.
Key Words: cardiovascular diseases carotid arteries epidemiology ultrasonography
| Introduction |
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We have previously shown9 that in healthy 35-year-old subjects, brachial artery diameter is correlated with risk factors for cardiovascular disease. Whether there is a relationship between arterial diameters and cardiovascular risk factors in a population at an age at which manifest atherosclerosis is more common has been studied less. In an elderly population (aged 59 to 72 years), luminal enlargement was related to risk factors such as male gender and systolic blood pressure but not to LDL cholesterol.10
Arterial diameters have usually been studied at the site of a vessel stenosis and discussed in terms of compensatory enlargement, whereas vessel diameters in plaque-free areas are studied less frequently. This study characterizes carotid artery IM thickness and diameter in the distal common carotid artery (CCA) with ultrasonography in a 55-year-old population and investigates the possible relationship between these measures and conventional risk factors for cardiovascular disease, such as gender, smoking, elevated blood lipids, and high blood pressure.
| Subjects and Methods |
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Fifty-seven of the 78 men (73%) and 47 of the 76 women (62%) were recruited as control subjects. Of these, 55 men and 45 women underwent a vascular ultrasound study. The ultrasound study was not performed in 2 men and 2 women because of sudden illness and the inaccessibility of ultrasound at a later time. The main reasons given for not participating in the study were lack of time (5 men, 6 women) and illness (4 men, 8 women). We were unable to establish contact with 9 subjects (6 men and 3 women).
Height and weight of the men and women were 1.80±0.07 m and 83±11 kg and 1.65±0.06 m and 70±13 kg, respectively. Body mass index (BMI) was 25.1±3.6 kg/m in the men and 25.8±2.8 kg/m in the women (P=0.30). None of the subjects had clinical signs or symptoms of infectious disease. They underwent a physical examination and answered standardized questions about medical history, smoking habits, and family history of disease. This was followed by donation of blood for analysis. The ethics committee of Karolinska Institute approved the study.
Methods
Blood pressure was taken in duplicate after 5 minutes of rest in
the sitting position. All measurements were taken between 7:30
AM and 9 AM by the same nurse and with the
same equipment.
Blood Chemistry
Blood was drawn on one occasion between 8 AM and 10
AM after 15 minutes' rest from subjects who had been
fasting since 9 PM the previous evening. Analysis
included leukocyte count, hemoglobin, platelet count, and blood
glucose and serum lipoproteins. Lipoproteins were analyzed for
serum cholesterol and serum triglycerides by
enzymatic techniques. HDL cholesterol was measured in serum
after precipitation of the apoB-containing lipoproteins. LDL
cholesterol was calculated by the Friedewald formula. Serum
was analyzed for the concentration of apoA-I, apoB, and
apo(a).
Risk Factor Score
We used the following scoring system for conventional risk
factors: 1 point for current smoking or ex-smoking; 1 point for
heavy smoking, defined as
10 years of smoking >10 cigarettes a day;
1 point for cholesterol level of >6 mmol/L; and 1
point for systolic blood pressure of
140 or
diastolic
95 mm Hg.
Ultrasound Methods
Ultrasound scans were made using a duplex scanner (Acuson
128XP) with a 7.0-MHz ART linear array transducer in a quiet,
semidarkened room with the subject supine. Subjects were asked not to
drink coffee or tea for at least 2 hours before the study. The left and
right CCAs were scanned. Plaques were defined as a local increase in
wall thickness of >1 mm.
IM Thickness
Left and right CCAs were examined. The subject's head was
tilted to position the CCA just proximal to the bulb horizontally
across the screen. Magnified pictures were frozen incidentally with the
R wave on the ECG. Only the far walls of the artery were used for
calculation.11 The IM thickness was defined as the
distance between the leading edge of the luminal echo to the leading
edge of the media/adventitia echo. IM thickness was measured over a
length of 1 cm just proximal to the bulb. This was done by using the
calipers and the trace function of the ultrasound system12
and calculating the mean IM thickness over this length.
CCA Diameter
The vessel diameter was measured on the same picture of the
distal CCA as the IM thickness. Measures were taken from the leading
edge of the near-wall echogenic IM line to the leading edge of the
luminal echo of the far wall.11 One measure was taken. All
measures were done by the same physician. The intraobserver coefficient
of variation for repeated measures of CCA diameter was 2%.
Statistics
Results are given as mean±SD. Univariate or
stepwise multiple linear regression analyses were used. Groups
were compared with Student's 2-tailed unpaired t test.
Probability levels of
0.05 were considered significant.
| Results |
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Blood Chemistry
Men had higher levels of triglycerides than women
(P=0.039). Women had higher levels of HDL
cholesterol (P<0.001), apoA-I
(P=0.017), and apoB/A-I (P<0.001).
Risk Factors
Smoking
Twelve men were smokers; 6 of these were heavy smokers (defined
above). Seven women were smokers; 3 of the 7 were heavy smokers.
Cholesterol
Twenty-two men and 22 women had cholesterol >6
mmol/L.
Blood Pressure
Twenty men and 13 women had systolic blood pressure of
140 mm Hg and/or diastolic blood pressure of
90 mm Hg.
| Carotid Ultrasound Investigation |
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IM Thickness
IM thicknesses in left and right CCAs were similar in men and
women.
CCA Diameter
The CCA diameter was larger in men than in women, with a mean
diameter of 6.3±0.6 mm in men versus 5.6±0.5 mm in women
(P<0.001). The men and women with plaques had larger
carotid artery diameter than those without plaques, 6.4±0.84 mm
versus 5.89±0.64 mm (P=0.008). They also had thicker
IM, 0.70±0.10 mm versus 0.62±0.07 mm (P<0.001).
There was no difference in blood lipids between those with and without
plaques.
| Correlations With Risk Factors |
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Gender, smoking, systolic blood pressure, BMI, platelet count, triglycerides, apoA-1, apoB, glucose, and occurrence of plaque was entered in a multiple regression analysis against CCA diameter. Gender, systolic blood pressure, BMI, apoB and occurrence of plaque had independent contributions to the equation.
Analyses were also made separately in men and women (because there was a difference in vessel size between men and women).
Men
The CCA diameter was correlated with a combined risk factor score
(r=0.40, P=0.005), systolic blood
pressure (r=0.34, P=0.011), platelet count
(r=0.287, P=0.033), apoB (r=0.30,
P=0.025), and occurrence of plaque (P=0.003).
When systolic blood pressure, platelet count, apoB,
occurrence of plaque, smoking, glucose, and BMI were entered in a
multiple regression analysis against CCA diameter, occurrence
of plaque was the only factor with an independent contribution to the
equation; other factors contributing to the equation were apoB,
systolic blood pressure, and platelet count.
Women
In women the CCA diameter was correlated with a combined
risk factor score (r=0.41, P=0.010),
systolic blood pressure (r=0.32,
P=0.033), BMI (r=0.56, P<0.001),
cholesterol (r=0.38, P=0.009),
triglycerides (r=0.36, P=0.14), apoB
(r=0,45, P=0.002), and apoB/A1
(r=0,43, P=0.003). When systolic blood
pressure, BMI, apoA-1, apoB, triglycerides, occurrence of
plaque, smoking, and glucose were entered into a multiple regression
analysis against CCA diameter, BMI and apoB had independent
contributions to the equation.
IM Thickness
IM thickness (Table 3
) was
correlated with systolic blood pressure (r=0.40,
P<0.001). In men IM thickness was correlated with a
combined risk factor score (r=0.29, P=0.047),
systolic blood pressure (r=0.50,
P<0.001), diastolic blood pressure
(r=0.40, P<0.001), and occurrence of plaque
(P=0.002). In women IM thickness was correlated with
diastolic blood pressure (r=0.34,
P=0.023) and hemoglobin (r=-0.35,
P=0.019).
|
All Subjects
IM thickness was entered into a multiple regression
analysis against gender, BMI, smoking,
triglycerides, apoA-1, apoB, systolic blood
pressure, occurrence of plaque, glucose, and hemoglobin.
Systolic blood pressure, plaque, gender, and hemoglobin had
independent contributions to the equation (Table 2
).
Correlations Between Variables
The mean IM thickness was correlated with carotid artery diameter
(r=0.32, P=0.001).
| Discussion |
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Vessel diameters generally increase with age. However, independent of age, there is a greater increase in coronary artery diameters in subjects with atherosclerosis than in subjects without atherosclerosis.13 Labropoulus and coworkers14 studied vessel diameters throughout the vascular system in 67±12-year-old subjects with and without atherosclerosis and found that all arteries dilate in the stage of early atherosclerotic plaque formation. They concluded that dilation of the artery occurs to preserve luminal area.
In the EVA study10 the carotid artery was examined in 1272 subjects aged 59 to 71 years. Increased IM thickness and plaque were accompanied by an increase in lumen diameter, and systolic blood pressure was related to lumen diameter. These results are similar to our findings in a somewhat younger population with a much lower prevalence of plaque.
The increase in arterial diameter in subjects with atherosclerosis is usually discussed in terms of compensatory enlargement, ie, compensatory in relation to stenoses, an increase in vessel diameter to preserve luminal area.14 However, none of the subjects in the present study had carotid stenosis, and the few subjects in whom a plaque was diagnosed had very small plaques (just over 1 mm). Furthermore, the relationship between vessel diameter and risk factors remained when the few subjects with plaque were excluded. This is in line with our previous studies in 35-year-old subjects (at an age long before atherosclerotic lesions usually appear), in which the brachial artery vessel diameter was correlated with risk factors for cardiovascular disease.9
Our findings suggest that the mechanism behind the increased carotid artery vessel diameter in the subjects with risk factors in the present study may be related to regulatory mechanisms present before compensatory enlargement to preserve lumen area and that vessel diameter may be used as a risk factor indicator.
There was a correlation between vessel diameter and IM thickness, but the CCA diameter correlated to more cardiovascular risk factors than IM thickness. The lack of correlation between IM thickness and some risk factors in our study could be due to the fact that relatively few subjects were studied, compared with previous risk factor studies which have included large number of patients. We have, however, excluded 1 main confounding factor, as the study population is of the same age.
It is possible that the vessel diameter in itself is a measure of vascular regulatory function. The regulation of flow and blood pressure is complex, and how it affects arterial diameters is only partly understood. A malfunction of any factor involved in vasoregulation, including baroreceptor function, could result in an increased vessel diameter. A possible reason for increased vessel diameter could be an increased flow. In the microcirculation there is evidence of an increased flow in hyperglycemia,17 18 19 and in the present study there was a correlation between carotid artery diameter and blood glucose levels.
The large vessel diameter may in itself lead to disturbed blood flow regulation, because a larger vessel will have a lesser ability to respond to increased blood flow by both endothelium-dependent and nonendothelium-dependent mechanisms9 20 and thereby possibly be a factor in promoting the development of atherosclerosis.
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| Acknowledgments |
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Received March 23, 1999; revision received May 17, 1999; accepted May 18, 1999.
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