Asian Cardiovasc Thorac Ann 2003;11:217-221
© 2003 Asia Publishing EXchange Ltd
Carotid Intima-Media Thickness and Coronary Artery Disease: an Indian Perspective
Gupta Hansa, MD,
Kartikeya Bhargava, MD,
Manish Bansal, MD,
Sharad Tandon, DNB,
Ravi R Kasliwal, DM
Noninvasive Cardiology, Escorts Heart Institute and Research Centre, New Delhi, India
For reprint information contact: Ravi R Kasliwal, DM Tel: 91 11 6825000 Fax: 91 11 6825013 email: rrkasliwal{at}hotmail.com Department of Cardiology, Escorts Heart Institute and Research Centre, Okhla Road, New Delhi – 110025, India.
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ABSTRACT
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To determine whether carotid intima-media thickness is associated with coronary artery disease and cardiovascular risk factors in the Indian population, carotid intima-media thickness was measured using high-resolution B-mode ultrasonography in 101 patients with coronary artery disease and 140 control subjects. Carotid intima-media thickness was measured at 3 predefined sites on each side. The maximum carotid intima-media thickness was significantly higher in the coronary disease group compared to the controls (1.02 vs. 0.80 mm). The average intima-media thickness was also significantly higher in the coronary disease group (0.82 vs. 0.67 mm). On multivariate logistic regression analysis, carotid intima-media thickness was the only factor found to be an independent predictor of coronary artery disease. There was a significant association between risk factor count and the average and maximum intima-media thickness values in the combined study population. These results indicate that raised values of average and maximum carotid intima-media thickness are significantly associated with the presence of coronary artery disease and this association is independent of the presence of other conventional cardiovascular risk factors.
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INTRODUCTION
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During the past 30 years, coronary artery disease (CAD) rates have doubled in both rural and urban India while they have been halved in the United States. By 2015, cardiovascular diseases are expected to account for 34% of male deaths and 32% of female deaths, amounting to a total of 1.5 million deaths.1 It is imperative to shift the focus to disease prevention rather than palliation. Prevention requires early identification of individuals at risk of developing cardiovascular disease but still clinically asymptomatic, so that intensive preventive measures may be instituted to arrest the progression of disease. Cardiovascular disease is the end result of the atherosclerotic process. The various diagnostic modalities used currently (exercise electrocardiography, stress echocardiography, thallium scanning, coronary angiography) can detect atherosclerotic disease only when it becomes well advanced and occlusive. Similarly, various risk-factor assessment scores can predict the risk of future cardiovascular events, but fail to identify the ongoing atherosclerotic process. Carotid intima-media thickness (IMT) measurement is a promising tool for detecting atherosclerosis in its pre-occlusive phase. Atherosclerosis is a generalized process that affects all arterial beds, and the risk factors for atherosclerosis are shared by all arterial beds including the carotid and coronary arteries.2 Thus atherosclerosis in the carotids should reflect coronary involvement, a fact that has been confirmed histologically by autopsy studies.2–4 Extracranial carotid arteries provide excellent and reproducible sites for IMT assessment because of accessibility, adequate size, and limited movement.5 Studies in Western patients have suggested that raised carotid IMT is an excellent predictor of the risk of future cardiovascular events, and it can also detect the presence of CAD.6–14 However, there are very limited data regarding the role of carotid IMT in Indians with CAD who differ from the Western population in cardiovascular risk profile, morbidity, and mortality.15–19 This study aimed to assess the role of carotid IMT in Indian patients with CAD.
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METHODS
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Two hundred and forty-one individuals from the inpatient and outpatient departments of the institute were enrolled in the study. They were divided into two groups: group 1 comprised 140 randomly selected individuals with no symptoms of CAD who came for a routine cardiology checkup; group 2 comprised 101 patients with established CAD. A stress test was performed in group-1 subjects to confirm the absence of significant CAD. The diagnosis of CAD was established in group 2 by a history of documented myocardial infarction or critical stenosis in at least one epicardial coronary artery on angiography. A long-term anti-atherosclerotic regimen is known to decrease IMT, and patients who have undergone any major cardiac intervention (angioplasty or coronary bypass grafting) are most likely to be compliant with a good anti-atherosclerotic regimen, therefore, such patients were excluded. Those with symptomatic cerebrovascular disease were excluded because occlusive carotid artery disease might interfere with IMT estimation. Patients with peripheral vascular disease were excluded because pulse-wave velocity estimation was included in the study for other purposes. The study was approved by the ethics committee of the institute, and informed consent was obtained from all subjects. Both groups underwent clinical evaluation, biochemical tests, and carotid IMT assessment. Stress testing (exercise electrocardiography or stress echocardiography) was carried out in everyone in group 1 and selected patients in group 2. Clinical examinations included blood pressure recording, assessment of cardiovascular status, height and body weight measurements. Biochemical assessment included fasting and postprandial blood sugar, and fasting lipid profile. Patients were evaluated for the presence and duration of conventional cardiovascular risk factors (hypertension, diabetes mellitus, family history of premature CAD, dyslipidemia, and current smoking). Hypertension was defined as systolic blood pressure > 140 mm Hg, or diastolic blood pressure > 90 mm Hg, or self-reported use of antihypertensive medications. Diabetes mellitus was defined as a fasting blood glucose > 126 mg•dL-1, or non-fasting blood glucose > 200 mg•dL-1 or pharmacological treatment for diabetes. Dyslipidemia was defined as low-density lipoprotein > 130 mg•dL-1, or high-density lipoprotein < 40 mg•dL-1, or triglycerides > 200 mg•dL-1. Family history was coded as positive if a first-degree relative had a coronary event before the age of 55 years in males or 65 years in females. Current smoking or tobacco use in any form was also considered a conventional risk factor.
Carotid artery scanning was performed with a high-resolution Sonos 5500 (Hewlett Packard, Inc., Anaheim, CA, USA) with a duplex B-mode scanner and a linear phased array transducer of 7.5 MHz frequency. Scanning was undertaken by a physician who was unaware of the clinical status of the subjects. Intima-media thickness was taken as the distance between the leading edge of the first echogenic line of the far wall of the carotid artery (lumen-intima interface) and the leading edge of the second echogenic line (media-adventitia interface). Measurements of IMT were made at end-diastole (peak of the R wave) at 3 segments on each side: the distal 1 cm of common carotid artery just before the bifurcation, the carotid bifurcation, and the proximal 1 cm of internal carotid artery. Measurements were taken only on longitudinal scans and not on transverse scans. For each individual, the maximum and average of all measurements at the 6 predefined sites were considered for further analysis.
The 2 groups were compared in terms of the number of risk factors, average IMT, and maximum IMT. Values were expressed as mean ± standard error or as a percentage. Student’s unpaired t test and the chi-squared test were used where appropriate. Interquartile ranges of average and maximum IMT were determined for each group. The risk factor count of each subject was calculated as the sum of conventional risk factors (diabetes, hypertension, dyslipidemia, smoking, and family history). The relationship of average and maximum IMT to risk factor count was analyzed using linear regression, and the Pearson correlation coefficient was determined. A p value < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 10.0 software (SPSS, Chicago, IL, USA).
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RESULTS
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The baseline characteristics of the study groups are shown in Table 1
. There was no statistically significant difference between the groups, except that diabetes mellitus was less prevalent in group 1 than group 2. The maximum and average carotid IMT values are shown in Table 2. The distribution of IMT values in the groups is depicted in Figures 1 and 2. The differences in maximum and average IMT between groups were highly significant (p < 0.0001). On multiple logistic regression analyses, maximum and average IMT values were found to be the only independent predictors (p < 0.001) of CAD among the variables studied (Table 3). In addition, a significant association was found between the number of conventional coronary risk factors in a particular individual and the average and maximum IMT (Table 4). The average IMT values and the risk-factor counts (for the entire study population) were linearly related with the regression equation: average IMT = 0.681 + 0.028 x risk-factor count (Pearson correlation coefficient, 0.222; p < 0.001). Similarly, the maximum IMT and the risk factor count were also linearly related with the regression equation: maximum IMT = 0.801 + 0.053 x risk-factor count (Pearson correlation coefficient, 0.28; p < 0.001); although the correlation coefficients were 0.222 and 0.28, the association was statistically significant.
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DISCUSSION
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Carotid IMT is a valid marker of early atherosclerosis and thus has the potential to detect cardiovascular disease in its subclinical phase. Both average and maximum IMT were used in analyses. Average IMT has the advantage of stability and reflects the extent of disease, whereas maximum IMT reflects more on the severity of atherosclerosis. Several studies have shown that carotid IMT is strongly associated with cardiovascular risk factors.15,20,21 It possibly reflects the cumulative deleterious effects of various cardiovascular risk factors over time. The Chennai Urban Population Study reported significantly raised mean IMT values in diabetic patients (0.95 ± 0.31 mm) compared to non-diabetic subjects (0.74 ± 0.14 mm; p < 0.001).15 Similarly, in the Atherosclerosis Risk in Communities (ARIC) study, carotid IMT was significantly higher in individuals with cardiovascular risk factors compared to normal controls.20 In our study, a significant linear relationship was also found between risk-factor count and both the average and maximum carotid IMT.
The role of carotid IMT as an indicator of CAD has been assessed in various studies.10–14 In the ARIC study which included 13,870 subjects, carotid far-wall IMT was consistently greater in those with clinical cardiovascular disease than in disease-free controls.10 Visona and colleagues11 showed that common carotid artery IMT in CAD patients (1.45 ± 0.95 mm) was significantly higher than in controls (0.87 ± 0.1 mm; p < 0.005). In a study of 75 male patients undergoing coronary angiography for chest pain, Geroulakos and colleagues12 showed that common carotid IMT was not only higher in patients with CAD, but also had a significant linear relationship with the number of involved coronary arteries (r = 0.44, p < 0.0001). In this respect, the results of our study are in agreement with previous studies showing a significant association between raised IMT and the presence of CAD. Moreover, maximum IMT and average IMT were the only independent predictors of the presence of CAD.
Our study has certain limitations. Absence of CAD was not documented by coronary angiography in group-1 subjects for ethical reasons. However, in view of the absence of symptoms suggestive of CAD in these individuals and the expectation that the stress test would detect the majority of cases of significant CAD, this should not unduly influence the results. Another limitation is that we did not enroll consecutive patients undergoing coronary angiography. Consequently, we cannot derive a positive or negative predictive value or a cut-off value of IMT for the detection of CAD.
It was concluded that the easy applicability and noninvasive nature of carotid B-mode ultrasonography make it suitable for use as a surrogate endpoint in measuring the atherosclerotic burden in asymptomatic subjects. Its role in predicting the risk of future cardiovascular events in Western populations has already been established by several large-scale prospective studies. Many of these studies have also shown that carotid IMT can indicate the presence and extent of CAD. This study suggests a significant association between IMT and the presence of CAD in the Indian population also. However, more data are needed to establish carotid IMT as a noninvasive tool for the detection of CAD in symptomatic or asymptomatic individuals.
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Acknowledgments
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We thank our statistician Mr S Shekhawat for his invaluable assistance in statistical analysis of the data.
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ABSTRACT
Introduction
