World Journal of Cardiovascular Diseases, 2013, 3, 414-418 WJCD
http://dx.doi.org/10.4236/wjcd.2013.36065 Published Online September 2013 (http://www.scirp.org/journal/wjcd/)
The impact of vascular risk factors multiplicity on severity
of carotid atherosclerosis—A retrospective analysis of 1969
Egyptian subjects
Essam Baligh1, Foad Abd-Allah2*, Reham Mohammed Shamloul2, Ehab Shaker2, Hani Shebly1,
Mohamed Abdel-Ghany1
1Department of Cardiovascular Medicine, Cairo University, Cairo, Egypt
2Department of Neurology, Cairo University, Cairo, Egypt
Email: *foadneuro@hotmail.com
Received 22 June 2013; revised 25 July 2013; accepted 15 August 2013
Copyright © 2013 Essam Baligh et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Background and Purpose: Carotid atherosclerosis has
been recognized as a major cause of stroke. The cur-
rent study aimed to describe the effect of multiplicity
rather than the type of vascular risk factors on sever-
ity of carotid atherosclerosis among a large sample of
Egyptian population. Methods: We analyzed the data
of 1969 Egyptian subjects, who proved to have extra
cranial carotid atherosclerotic disease by duplex
scanning at the vascular laboratories of Cairo Uni-
versity Hospitals. Demographic, clinical data and
causes of referral were recorded and correlated with
ultrasound findings. Atherosclerotic indices, namely
IMT, plaque number and percentage of stenosis were
used for evaluation of severity of carotid atheroscle-
rosis. Furthermore, subjects were classified according
to multiplicity of major atherosclerotic risk factors
and multivariate regression analysis was performed
to detect independent predictors of significant carotid
disease. Results: Out of 1969 subjects with proved
signs of extracranial carotid atherosclerosis by duplex
ultrasonographic scan, 225 (11.4%) showed hemody-
namic significant stenosis (50%). Multiplicity of risk
factors beyond the age of 50 years was the strongest
predictor of significant stenosis. Conclusion: Age
more than 50 years and multiplicity rather than the
type of risk factors were the strongest predictors of
significant carotid atherosclerotic disease (CAD).
Keywords: Carotid; Atherosclerosis; Risk Factors;
Duplex; Carotid Stenosis
1. INTRODUCTION
Identification of risk factors in asymptomatic and/or
symptomatic patients is the preferred method to improve
the quality of clinical practice and patient care. It is well
known that multiple risk factors contribute to athero-
sclerosis that causes cerebrovascular disease (CVD) and
these risk factors interact multiplicatively [1,2].
Ultrasound measurements of IMT and plaque in the
carotid arteries are important not only for the assessment
of structural alterations but also because the extent of
atherosclerosis in these vessels reflects the severity of
arterial damage in other vascular territories [3].
Recent studies have suggested that clustering of sev-
eral risk factors may strongly promote increased intima
media thickness in the carotid arteries [4,5] and therefore
might be a strong predictor for future stroke [6-8]. Nev-
ertheless, the significance of multiple risk factors and
their relation to atherosclerosis has been mainly exam-
ined in European, American and Asian population [9]. It
remains to be clarified whether multiple risk factors are
related to severity of atherosclerosis and/or are predictive
to atherosclerosis of the carotid arteries in the Egyptian
population.
2. MATERIALS AND METHODS
2.1. Study Population
This study is a retrospective analytical study based on the
clinical and duplex ultrasound finding of 1969 subjects
who proved to have extracranial carotid atherosclerotic
disease at vascular laboratories of Cairo University hos-
pitals during period from January 1st 2008 to January 1st
2010. The study population recruited from cases referred
to vascular ultrasound laboratories due to:
*Corresponding author: Foad Abd-Allah, Associate professor o
f
N
eurology, Cairo University, Egypt.
OPEN ACCESS
E. Baligh et al. / World Journal of Cardiovascular Diseases 3 (2013) 414-418 415
1) Cerebrovascular symptoms either stroke or
TIAs (sym- ptomatic group)
2) Checkup either routine or before coronary by-
pass graft surgery (Asymptomatic group )
2.2. Clinical Data and Cardiovascular Risk
Factors
The following data were collected from each individual
patient prior to ultrasound examination: Age, Sex, Hy-
pertension, Diabetes Mellitus, Dyslipidemia, Obesity,
Smoking, and history of Ischemic heart disease (IHD).
Hypertension was defined as blood pressure >140/90 mm
Hg for 2 repeated measurements or if a subject was on
antihypertensive medications [10]; diabetes mellitus as
repeated fasting plasma glucose > 126 mg/dl or a patient
on anti-diabetic measures [11]; dyslipidemia as fasting
serum total cholesterol of 200 mg/dl, LDL cholesterol
of 130 mg/dl, HDL cholesterol of <40 mg/dl for men
and <50 mg/dl for women or triglyceride concentration
of 150 mg/dl or if the subject was on lipid-lowering
drugs or gave a history of established diagnosis of dys-
lipidemia [12]. Obesity was defined as a body mass in-
dex of 30 [13]. History of cigarette smoking was posi-
tive if subjects smoked 10 cigarettes per day for >10
years and ischemic heart disease was defined as evi-
dence of the disease based on ECG, echocardiography,
stress test or coronary angiography or if the patient was
known to have ischemic heart disease.
2.3. Ultrasonographic Data (Carotid Duplex Scan)
Carotid duplex scanning was performed by qualified vas-
cular operators using Philips HDI 5000 machines. A
high-frequency (7- to 10-MHz) linear array transducer
was employed to scan the carotid from the most proximal
common carotid artery (CCA) to the internal carotid ar-
tery (ICA) as far as the mandible permitted. The exami-
nation starts by a B-mode transverse scanning of the
vessels so as to examine the arterial wall morphology,
detect intima media changes and presence of atheroma-
tous plaques.
2.3.1. Intima Media Thickness
Longitudinal scanning and quantification of the intima
media thickness (IMT) at the distal far wall of the CCA
was done, IMT 1.0 mm was considered abnormal [14].
2.3.2. Assessment of Extra-Cranial Carotid Plaques
Plaques were defined by the presence of focal, severe
wall thickening (IMT > 2 mm). Echogenicity and surface
characteristics were evaluated and number of plaques
was recorded in each subject [15].
2.3.3. Degree of Carotid Artery Stenosis
Pulsed Doppler signals were routinely recorded from the
CCA just proximal to the bifurcation, the origin of the
external carotid artery, proximal, mid and if accessible
distal ICA. They were recorded in the longitudinal view
with less than 60˚ insonation angle. PSV and end-dia-
stolic velocities were recorded at the proximal ICA, the
distal CCA and the PSV ICA/CCA ratio was calculated.
In case of a stenosis on B-mode and color Doppler im-
aging, the Doppler signal was recorded from the site of
maximum stenosis, i.e. from the area of maximum flow
turbulence on color Doppler imaging. The degree of
stenosis was primarily assessed according to the Doppler
information. Hemodynamically insignificant plaque (<
50% stenosis) was diagnosed if plaque was detected on
B-mode image and PSV was <125 cm/s. Moderate ICA
stenosis (50%) was diagnosed by PSV ICA 125 cm/s
and PSV ICA/CCA ratio 2, severe ICA stenosis (70%)
according to NASCET criteria [16] by PSV ICA 230
cm/s and PSV ICA/CCA ratio 4, and critical ICA
stenosis (>80%) by end-diastolic velocity 140 cm/s.
ICA occlusion was diagnosed when occluding material
was visualized in B-mode, color and pulsed Doppler
signal was absent and diastolic velocity in the ipsilateral
CCA was low or absent. Carotid arteries were considered
normal if the intima-media thickness was <1.0 mm, no
plaque detected and peak systolic velocity at the pro-
ximal ICA (PSV ICA ) was less than 125 cm/s. Carotid
atherosclerotic disease was considered present if the in-
tima-media complex showed diffuse thickening (1.0
mm) or if carotid plaques were detected.
3. STATISTICAL ANALYSIS
Data were described as mean ± standard deviation (SD),
range, frequencies (number of cases) and relative fre-
quencies (percentages). Categorical variables were ex-
pressed as percentages and continuous variables were
expressed as mean ± SD, with a 95% confidence interval
(CI). Comparative statistics were performed with Stu-
dent’s t test, Mann-Whitney U or Χ2 test as appropriate.
Multivariate regression analysis was performed to detect
independent predictors of carotid atherosclerosis and
carotid stenosis. A probability value (p value) less than
0.05 was considered statistically significant. All statistic-
cal calculations were performed using Microsoft Excel
version 7 and SPSS version 15 for MS windows (Statis-
tical Package for the Social Science, SPSS Inc., Chicago,
Ill., USA).
4. RESULTS
A total of 1969 subjects were included in the study. Age,
gender and the number of risk factors are demonstrated
in Table 1.
Carotid Atherosclerotic Disease (CAD) was defined as:
IMT 1 mm and/or presence of plaques. Increase IMT
Copyright © 2013 SciRes. OPEN ACCESS
E. Baligh et al. / World Journal of Cardiovascular Diseases 3 (2013) 414-418
416
Table 1. Demographic data and distribution of risk factors
among study population.
Item
Mean age ± SD 61.89 ± 9.97
Males
Females
1460 (74%)
509 (26%)
Number of risk factors
No risk
1 risk
2 risks
3risks
10 (0.5%)
134 (6.8%)
434 (22%)
1391 (70%)
Smoking 799 (41%)
IHD 905 (46%)
HTN 835 (42%)
DM 635 (32%)
Obesity 227 (12%)
Dyslipidemia 96 (5%)
only without associated plaques were detected in
(15.08%) and presence of carotid plaque existed in
(84.91%). Hemodynamic significant stenosis 50% was
found in 225 patients (11.4%) of subjects. Among those
patients 155 (7.87%) had moderate stenosis (50% -
<70%), 67 (3.4%) had severe carotid artery stenosis
(70%) and 3 (0.15%) subjects only showed total occ-
lusion (Table 2).
Multivariate stepwise logistic regression analysis
showed that age > 50 followed by presence of multiple
risk factors (3 risk factors) were the strongest predictors
for the hemodynamic significant stenosis (50%) and
severe stenosis (70%) (Table 3).
5. DISCUSSION
This study highlights the strong relationship between
aggregation of major cerebrovascular risk factors and
severity of carotid atherosclerosis among a large sample
of Egyptian subjects. This retrospective analysis showed
a strong correlation between age and multiplicity of risk
factors (3) on one side and severity of carotid athero-
sclerosis on the other side.
In agreement with our results, several studies include-
ing previous reports from Egypt found that among all
risk factors investigated, age has by far the strongest in-
dependent association with carotid atherosclerosis. Age
may affect the pathogenesis of atherosclerosis by induc-
ing physiological vascular changes and by increasing the
exposure to traditional risk factors [17-19].
It has been suggested that different risk factors domi-
nate in different stages of atherosclerosis. Risk factors
found to have a stable effect across age could be impor-
tant in initiating atherosclerosis, whereas risk factors
Table 2. Duplex measures of different degrees of Carotid
atherosclerosis among the study population.
Item Overall subjects
(n = 1969)
IMT 1mm
(no associated plaques) 297 15.08%
Atherosclerotic plaque +ve1672 84.92%
<50%
50% :
50% - <70%
70%
Totally occluded
1447
225
155
67
3
73.49%
11.4%
7.87%
3.4%
0.15%
Table 3. Logistic regression analysis, showing predictors of the
hemodynamic significant stenosis (50%) and severe stenosis
(70%).
Risk
factors
Hemodynamic significant
stenosis (50%)
Severe stenosis
(70%)
ORLower Upperp
value OR Lower Upperp
value
Age > 502.04021.18013.5273<0.01 2.0945 1.006 4.3607<0.01
3 RF1.87451.31822.6655<0.01 2.1327 1.1085 4.1031<0.01
Significant p value < 0.05, RF = Risk Factor.
which have an increasing effect with age, such as hyper-
tension and hyperlipidemia, may be more associated with
the progression of atherosclerosis [20].
In the current study, the only two predictors of signi-
ficant (50%) and severe stenosis (70%) were age and
multiplicity of risk factors. This finding supports the
view that multiple risk factors have a synergistic effect
on the risk and severity for CAD, as it has been demon-
strated by others [21].
Our study proved that hemodynamic significant steno-
sis 50% was found in (11.4%) of subjects, (7.87%) had
moderate stenosis (50% - <70%), (3.4%) had severe
carotid artery stenosis (70%) and (0.15%) subjects only
showed total occlusion. This finding confirms the fol-
lowing; there is a trend increasing in the incidence of sig-
nificant carotid stenosis among Egyptians compared to
previously published data. Comparing this finding with
one of the American studies, the Cardiovascular Health
Study [22] examined 5441 community-dwelling people
aged 65 years. Carotid stenosis >50% was found in 7%
of the men and 5% of the women, and 1.2% of men and
1.1% of women had a 75% - 99% stenosis. The current
data confirm that Atherosclerosis among Egyptians is
rising and this is a call for health authorities to monitor
the noncommunicable diseases and invest into health
education and prevention programs.
Our study was underpowered to identify the role of
gender, due to the high prevalence of males in our sam-
ple (72.5%), therefore, an under representation of high-
Copyright © 2013 SciRes. OPEN ACCESS
E. Baligh et al. / World Journal of Cardiovascular Diseases 3 (2013) 414-418 417
risk women is also possible. However, the higher preva-
lence of atherosclerotic lesions in males was in accor-
dance with that found in other studies as the Cardiovas-
cular Health Study which showed that among the elderly
(65 years), women have less carotid atherosclerosis
than men. The Atherosclerosis Risk in Communities
(ARIC) Study [23] revealed that the carotid wall in-
tima-media thickness is greater in men than in women
aged 45 to 64 years. Caplan et al. [24] demonstrated that
female may be more susceptible to intracranial arterial
occlusive disease than extracranial carotid disease [25].
In conclusion, according to the current study, multiple
risk factors are more predictive than a single risk factor
for atherosclerosis in the carotid arteries. Since unfavor-
able risk factor profile is associated with an increase in
the severity of atherosclerosis and age is non modifiable,
our study highlights the importance of controlling modi-
fiable risk factors early in life which may retard athero-
sclerosis development and hence delay the onset of pro-
gression to clinical cerebrovascular insults.
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