Background– cardiovascular disease (CAD)is one of the leading causes of morbidity and mortality. There is a need to diagnose CAD at subclinical stage so that appropriate lifestyle and pharmacological measures be taken to prevent CAD and its complications. This study was done to find association between CIMT and presence and severity of CAD. Method -It was a case control study in which120 subjects were enrolled and divided into 2 groups which includes 60 cases and 60 controls respectively. Cases comprise individuals that coronary angiography proven CAD and controls include asymptomatic subjects with normal ECG and echocardiogram or individuals with normal coronary angiography study. Carotid artery intima media thickness was measured in all 120 subjects using carotid artery doppler. Result -The mean age of cases and controls was 62.6 years and 60.05 years respectively. Male to female ratio was not statistically significant (cases1:1 and controls and was 1.6:1). The mean CIMT of right and left carotid artery in cases were1.06±0.26 mm and 1.06±0.28 mm respectively which was significantly higher than mean CIMT of controls which was0.63±0.23 mm and 0.60±0.28 mm on respective sides. Mean CIMT in patients of single, double and triple vessel disease on coronary angiography were1mm, 1.07mm and 1.14mm in right carotid artery and 0.97 mm, 1.04 mm and 1.2mm in left carotid artery respectively which depicts that higher CIMT was associated with increased number of vessels involvement based on coronary angiography. Additionally, CIMT exhibited significant associations with established cardiovascular risk factors including DM, smoking, hypertriglyceridemia, hypercholesterolemia, low HDL levels, and elevated LDL levels. Conclusion Increase in CIMT is associated with both the presence and severity of coronary artery disease. Therefore, measuring CIMT may be a valuable tool for predicting CAD at an early stage.
CAD is one of the leading causes of morbidity and mortality in world(1). It is characterized by inadequate supply of oxygen and blood to myocardium due to mismatch between coronary demand and supply. It may present with various symptoms such as chest pain, shortness of breath, diaphoresis, nausea, epigastric pain etc. It can be diagnosed based on ECG, echocardiogram, cardiac biomarkers,coronary CT angiography, cardiac MRI, coronary perfusion scintigraphy, coronary angiography. Among them, coronary angiography is the gold standard investigation for diagnosing CAD(2) but the procedure is invasive, expensive and associated withradiation exposure, patient discomfort and potentially serious adverse events. Atherosclerosis is a systemic condition, and evaluating the carotid arteries can provide valuable insights into overall cardiovascular risk. Their superficial location makes them easily accessible via doppler ultrasound assessment which is safe, non-invasive and pocket friendly way of evaluating atherosclerosis without serious complications (3). Also, atherosclerotic disease has already reached at an advanced stage of involvement when patient presents with clinical symptoms. Thus, the benefit obtained from interventions beyond that point is limited which depicts the need for diagnosing CAD before onset of clinical symptoms that is in subclinical stage. Carotid artery intima media thickness is a marker of subclinical atherosclerosis and can detect atherosclerosis at an earlier stage by carotid artery doppler study.
In our study, we aimed to find the association of CIMT with presence of CAD and its association with number of vessels involved on coronary angiography in CAD patients.
One hundred twenty subjects attending Medicine and Cardiology department of Rajendra Hospital Patiala were included in the study. Informed consent was taken from them in their vernacular language. The subjects were categorized into two groups- cases and controls.
Cases included individuals that had undergone coronary angiography and percutaneous coronary intervention or coronary artery bypass graft. Controls include asymptomatic healthy adults with normal ECG and echocardiogram or individuals with coronary angiography reporting normal study. Patients with history of TIA, stroke, neck mass, large vessel vasculitis, neck surgery or cervical trauma were excluded from the study.
Carotid artery doppler was performed in all 120 individuals using a Phillip Epiq 5 USG machine using linear probe with transducer L12-3 available in our hospital. All subjects were examined in supine position with head slightly extended to opposite direction of carotid artery being examined. Both right and left common carotid arteries were examined. The distance between two echogenic lines separated by echolucent space in arterial wall was used to calculate CIMT. The criteria for abnormal CIMT is>1mm (4).
STATISTICAL ANALYSIS
The data generated was filled in Microsoft excel spreadsheet and was analyzed. Quantitative variables were expressed as mean ± standard deviation and qualitative variables as percentage. Student t-test or Mann-Whitney U-test were applied for between-group comparisons of continuous variables while the chi-square test was used for between-group comparisons of categorical variables. A p value ≤ 0.05 was considered statistically significant.
The mean age of cases and controls were 62.6 years and 60.05 years respectively and was statistically non-significant. The ratio of male to female is 1.6:1 and there was no difference in distribution of cases and controls based on age and gender distribution with p value of 0.075 and 0.198 respectively. There was higher prevalence of hypertriglyceridemia in cases than controls and the difference was statistically significant(p=0.00034). More number of individuals had LDL level equal or above 130mg/dl in cases than controls and the difference was statistically significant. In our study, there was increased prevalence of low HDL level (HDL<40mg/dl) in cases than controls and it was statistically significant. The difference in prevalence of hypercholesterolemia, hypertension, diabetes and history of smoking were statistically insignificant. The demography of the population and prevalence of various cardiovascular risk factors was given in table 1.
TABLE 1: DEMOGRAPHIC CHARACTERSTICS AND PREVELANCE OF CARDIOVASCULAR RISK FACTORS AMONG THE PARTICIPANTS
|
CASES |
CONTROLS |
P value |
Mean Age |
62.68years |
60.05years |
0.075 |
Male/female ratio |
1:1 |
1.6:1 |
0.198 |
Prevalence of diabetes |
36(60%) |
26(43.3%) |
0.068 |
Prevalence of hypertension |
26(43.3%) |
22(36.7%) |
0.456 |
Prevalence of hypertriglyceridemia |
32(53.3%) |
13(21.7%) |
0.00034 |
Prevalence of hypercholesterolemia |
31(51.7%) |
21(35%) |
0.065 |
Presence of Serum LDL level >130mg/dl |
34(56.7%) |
23(38.3%) |
0.044 |
Presence of serum HDL <40mg/dl |
29(48.3%) |
8(30.8%) |
0.00003 |
Presence of History of smoking |
25(41.66%) |
16(26.6%) |
0.0832 |
The mean CIMT in right and left carotid artery among cases were 1.06mm on either side while mean CIMT on right and left side in controls were 0.63mm and 0.60mm respectively as shown in table 2. The mean CIMT was higher in cases than controls and the difference was statistically significant based on ANOVA test.
TABLE 2: MEAN CIMT(BOTH SIDES) OF CASES AND CONTROLS
|
RIGHT MEAN CIMT |
LEFT MEAN CIMT |
Controls |
0.63(±0.23) |
0.60(±0.21) |
Cases |
1.06(±0.26) |
1.06(±0.28) |
The mean CIMT in subjects with normal angiography were 0.59 mm and 0.57 mm in right and left carotid artery respectively. The mean right sided CIMT in single, double and triple vessel disease was 1mm,1.07mm and 1.14mm while mean CIMT in left carotid artery in single, double and triple vessel disease was 0.97mm, 1.04mm and 1.2mm respectively. The mean CIMT increases as the number of vessels involved on angiography increases and the difference was statistically significant using ANOVA test.
TABLE 3- DISTRIBUTION OF MEAN CIMT (mm) BASED ON NUMBER OF VESSELS INVOLVED ON CORONARY ANGIOGRAPHY
Number of vessels involved on coronary angiography |
Number of Individuals who had undergone coronary angiography |
RIGHT MEAN CIMT (mm) |
LEFT MEAN CIMT (mm) |
Normal study |
14 |
0.59 |
0.57 |
Single vessel |
21 |
1.00 |
0.97 |
Double vessel |
22 |
1.07 |
1.04 |
Triple vessel |
17 |
1.14 |
1.20 |
TABLE4–ASSOCIATION OF CIMT (of both sides) WITH CARDIOVASCULAR RISK FACTORS AMONG THE PARTICIPANTS
|
Number of individuals |
Right CIMT more than 1mm |
Left CIMT more than 1mm |
||
|
|
|
P value |
|
P value |
Prevalence of Diabetes |
62(51.7%) |
30(48.3%) |
0.018 |
24(38.7%) |
0.27 |
Presence of LDL level >130mg/dl |
57(47.5%) |
25(43.9%) |
0.17 |
25(43.9%) |
0.02 |
Presence of HDL <40mg/dl |
37(30.8%) |
20(54.05%) |
0.01 |
17(45.94%) |
0.05 |
Presence of Hypercholesterolemia(>200mg/d) |
52(43.3%) |
22(42.23%) |
0.34 |
23(44.23%) |
0.027 |
Prevalence of Triglyceride level (>150mg/dl) |
45(37.5%) |
23(51.1%) |
0.0175 |
21(46.6%) |
0.016 |
Prevalence of Hypertension |
48(40%) |
18(37.5%) |
1 |
16(33.3%) |
1 |
Presence of smoking |
41(34.16%) |
23(56.09%) |
0.002 |
19(46.3%) |
0.029 |
According to Table 4, there was significant association between the prevalence of diabetes and right CIMT (p = 0.018). The percentage of subjects with LDL level ≥ 130mg/dl with left CIMT >1mm were 43.9% and there was statistically significant association between high LDL level and left CIMT. The association between hypercholesterolemia and left CIMT>1mm was also statistically significant with p=0.027. There was significant association between serum triglyceride level and CIMT of both right and left carotid arteries. The association of history of smoking with CIMT was also significant on both sides.In contrast to above findings the association between hypertension and CIMT was found to be statistically insignificant.
ROC curve assessment of the diagnostic accuracy of right and left CIMT in predicting CAD depicts that right CIMT ≥ 0.77 mm has sensitivity and specificity of 83% and 75% respectively and left CIMT ≥ 0.755 has sensitivity and specificity of 85% and 83.3% in predicting CAD.
In our study, the mean age of cases and controls were 62.6 years and 60.05 years and right CIMT increases with increase in age of individual in cases and the ratio of male to female is 1.6:1 and there was no significant association between gender and CIMT respectively.
Our study shows significantly higher CIMT in patients of CAD as compared to normal individuals. Mean CIMT in the right and left carotid arteries was 1.06 ± 0.26 mm and 1.06 ± 0.28 mm in cases, versus 0.63 ± 0.23 mm and 0.60 ± 0.21 mm in controls (ANOVA, p < 0.05).As the thickness of carotid intima-media increases,more number of coronary vessels involvement was observed on coronary angiography. For the right carotid artery, CIMT was 1.00 mm in single-vessel disease, 1.07 mm in double-vessel, and 1.14 mm in triple-vessel disease. Corresponding values for left carotid CIMT were 0.97 mm, 1.04 mm, and 1.20 mm, indicating a positive correlation between CIMT and coronary disease severity.
Similar results were reported by Coskun et al study (5)and Khatri JK et al study (6). Coskun et al study includes 100 patients with stable angina pectoris and documented ischemia on stress test and divided it into 2 groups with non -critical and critical coronary obstruction and CIMT was measured in 2 groups. The mean CIMT was 0.78 ± 0.21 mm in group 1 and 1.48 ± 0.28mm in group 2.This study found that increased intima-media thickness of carotid arteries were seen with increased extent of CAD.
Khatri JK et al study (6)also reported that the mean CIMT was significantly correlated to number of obstructed coronary arteries. The mean CIMT in patients with single vessel disease, double vessel disease and triple vessel disease was 0.58±0.16mm, 0.718±0.206mm and 0.934± 0.301 mm respectively which was significantly higher than controls.
We also studied the association between various cardiovascular risk factors with CIMT (both right and left side). The association between diabetes and right CIMT was found to be significant with p value=0.018 and the association of low HDL level (<40mg/dl) was also found to be significant with right CIMT while no association was seen between HDL level and left carotid artery.
There was significant association between left CIMT with hypercholesterolemia (serum cholesterol≥200mg/dl) and raised LDL level(≥130mg/dl). Hypertriglyceridemia and history of smoking was associated with CIMT on both sides. In our study, hypertension was not found to be associated with right and left CIMT.
Our study depicts right CIMT ≥ 0.77mm was shown to indicate likelihood of CAD with sensitivity and specificity of 83% and 75% respectively and left CIMT ≥ 0.755mm was indicating CAD likelihood with sensitivity and specificity of 85% and 83.3% respectively using ROC curve analysis. We propose that right CIMT value ≥ 0.77 and left CIMT value ≥ 0.755 will increase the detection rate of CAD.
We have observed that association of CIMT with different CV risk factors may not be present on both carotid arteries all the time and may be seen unilaterally. Therefore, it is important to determine CIMT of both sides to predict the presence of CAD in individuals.
Inour study, association of CIMT with coronary angiography proven CAD patients with asymptomatic healthy controls was studied and concluded a significant association between them. Furthermore, our study found that CIMT increases as the number of vessels involved on coronary angiography increases. Therefore, assessment of CIMT may be used to predict the presence of CAD among the patients with cardiovascular risk factors. CIMT was also significantly associated with diabetes mellitus, hypertriglyceridemia, hypercholesterolemia, HDL level,LDL level and smoking history inour study.
LIMITATION
The limitation of our study was small number of participants included in our study population and single center study. Therefore, further studies with large number of participants may be required to validate this hypothesis and overcome the limitations of our study.
CONFLICT OF INTEREST
The study was cleared by Institutional ethical committee and there is no conflict of interest to declare.