A Comparison of Segment-Specific and Composite Measures of Carotid Intima-Media Thickness and their Relationships with Coronary Calcium

Abstract

Aims: The utility of carotid intima-media thickness (cIMT) as a marker for coronary heart disease is under heavy debate. This is predominantly due to the lack of a standard definition of cIMT, leading to inconsistent results. We investigated and compared the relationships of five different measures of cIMT with coronary calcium.

Methods: Japanese men aged 40-79y ( n=869) from Shiga Epidemiological Study of Subclinical Atherosclerosis were examined. Mean cIMT was measured in three segments of the carotid arteries: common carotid artery (CCA_mean), internal carotid artery (ICA_mean) and bifurcation (Bif_mean). Mean cIMT of average values (Mean cIMT) and mean cIMT of maximum values (Mean-Max cIMT) of all segments combined were assessed. Coronary calcium was assessed as coronary artery calcification (CAC). Ordinal logistic regression was used to determine the odds ratio (OR) of higher CAC per 1 standard deviation higher cIMT measure. Analyses were adjusted for cardiovascular covariates and stratified by age quartiles.

Results: All cIMT measures had positive associations with CAC (p＜0.001): [OR, 95% Confidence Interval]: ICA_mean [1.23, 1.07-1.42], CCA_mean [1.27, 1.08-1.49], Bif_mean [1.33, 1.15-1.53], Mean cIMT [1.42, 1.22-1.66], and Mean-Max [1.50, 1.28-1.75]. In age-stratified analyses, only Mean-Max cIMT maintained a significant relationship with CAC in every age quartile (p＜0.05), while CCA_mean had some of the weakest associations among age quartiles.

Conclusions: Mean-Max cIMT had consistently stronger associations with coronary calcium, independent of important confounders, such as age. The most oft-used measure, CCA_mean, was no longer associated with coronary calcium after age-adjustment and stratification.

Keywords: Carotid artery; Carotid atherosclerosis; Carotid intima-media thickness (cIMT); Coronary artery calcification (CAC); Coronary atherosclerosis.

Supplementary Fig.1. A schematic of the carotid artery segments and the walls used for the measurement of carotid intima-media thickness (cIMT)

CCA=common carotid artery, Bif=bifurcation, ICA=internal carotid artery. Of each segment, near walls are the carotid walls closest to ultrasound scanner and far walls are the farthest. A total of four walls of the artery were measured (indicated by numbers 1-4). With the exception of the far wall of the bifurcation, all near and far walls were measured with lengths of 1cm proximal to the bifurcation. Vertical lines indicate distinction between the segments.

Fig.1. Odds ratio for higher CAC score with a 1 standard deviation higher cIMT measure

Odds Ratios (OR) were determined using ordinal logistic regression for higher CAC grouping: 0-10, ＞10-100, ＞100-400, and ＞400 Agatston score. Covariates in Model 1: Computed tomography (CT) machine used (EBCT/MDCT); Model 2: CT machine＋age; Model 3: CT machine＋age＋cardiovascular disease (CVD) risk factors (body mass index, systolic blood pressure, hypertension medication (yes/no), non-high-density lipoprotein cholesterol, hemoglobin A1c, diabetes (yes/no), current drinker (yes/no), drinking amount, current smoker (yes/no), and smoking amount; Model 4: Model 3＋ICA _mean , CCA _mean , and Bif _mean .

Fig.2. Odds ratio for higher CAC score with a 1 standard deviation higher cIMT measure

Odds Ratios (OR) were determined using ordinal logistic regression for higher CAC grouping: 0-10, ＞10-100, ＞100-400, and ＞400 Agatston score. Covariates in the model were computed tomography machine used (EBCT/MDCT), age, and cardiovascular disease (CVD) risk factors (body mass index, systolic blood pressure, hypertension medication (yes/no), non-high-density lipoprotein cholesterol, hemoglobin A1c, diabetes (yes/no), current drinker (yes/no), drinking amount, current smoker (yes/no), and smoking amount). Age quartiles were (1) 40.2-57.7 y, (2) 57.9-64.1 y, (3) 64.1-71.5y, (4) 71.5- ~80 y.

Supplementary Fig.2.

Odds ratio for higher CAC score with a 1 standard deviation higher cIMT measure in SESSA men aged 40 to ~80 years, (including those on lipid medication), n =995 Odds Ratios (OR) were determined using ordinal logistic regression for higher CAC grouping: 0-10, ＞10-100, ＞100-400, and ＞400 Agatston score. Covariates in the model were computed tomography machine used (EBCT/MDCT), age, and cardiovascular disease (CVD) risk factors (body mass index, systolic blood pressure, hypertension medication (yes/no), non-high-density lipoprotein cholesterol, hemoglobin A1c, diabetes (yes/no), current drinker (yes/no), drinking amount, current smoker (yes/no), smoking amount and lipid medication (yes/no)). Age quartiles were (1) 40.2-58.2 y ( n =248), (2) 58.2-64.3 y ( n =249), (3) 64.3-72.0y ( n =249), (4) 72.0- ~80 y ( n =249).