The impact of vascular risk factors multiplicity on severity of carotid atherosclerosis—A retrospective analysis of 1969 Egyptian subjects

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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: *[email protected]

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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