Carotid intima-media thickness as surrogate marker: the clouding effect of submillimetric inaccuracies
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To the editor,
Shin et al. [1] published recently a study titled "Association between metabolically healthy obesity and carotid intima-media thickness in Korean adolescents with overweight and obesity" investigating the relationships among preclinical atherosclerosis, metabolic phenotypes, and cardiometabolic risk factors (CMRFs) in overweight and obese adolescents. As surrogate marker for preclinical atherosclerosis the authors used the carotid intima-media thickness (cIMT) measured by ultrasound [1]. The study included 111 participants (80 males and 31 females), 23 (20.7%) were classified as metabolically healthy obesity (MHO) and 88 (79.3%) as metabolically unhealthy obesity (MUO) [1]. The cIMT values did not differ between the MHO and MUO groups (mean, 459.7±9.7 μm vs. 470.1±5.8 μm; maximum 506.8±13.6 μm vs. 512.7±6.7 μm) [1]. When the participants were categorized into 3 groups based on tertiles of mean cIMT values: 40 (36.0%) low tertile (≤445.0 μm), 34 (30.6%) mid tertile (456.7–480.0 μm), and 37 (33.3%) high tertile (≥481.0 μm), it showed that the high cIMT tertile group exhibited higher systolic blood pressure than that demonstrated by the low cIMT tertile group (123.7±2.1 mmHg vs. 116.9±1.6 mmHg, P=0.028) [1]. The authors found that cIMT was associated with age and BMI, but did not differ significantly according to metabolic phenotype or presence of CMRFs (mean, 459.7±9.7 μm vs. 470.1±5.8 μm; maximum 506.8±13.6 μm vs. 512.7±6.7 μm) [1]. There are 2 main issues with the study of Shin et al. [1], which the author of this letter observes unfortunately too frequently in cIMT based studies and that lead to a clouding of the results: (a) measurement protocol and (b) cardiac synchronization. Point (a): Shin et al. [1] measured in one predetermined carotid artery (CA) section, the far wall of the common carotid artery (CCA) in proximity of the carotid bifurcation. Importantly to mind is that a single location cIMT measurement, namely at the far wall of the CCA [2] may coincide with a normal CA segment, disregarding potential atherosclerotic vessel segments outside of the measured area.
Kolaszyńska and Lorkowski [3] wrote in their paper, "Symmetry and asymmetry in atherosclerosis, the following, "Arterial regions mostly affected by atherosclerotic lesions are bifurcations, branch points and major curvatures. …Within the carotid tree atherosclerotic plaques mostly form in the common carotid and internal carotid artery… symmetry and asymmetry within the human vascular system play a crucial role in understanding arterial diseases, including atherosclerosis." [3] Given this complex presentation of atherosclerosis [3,4] including different CA segments for cIMT evaluation, e.g., near/far walls of the CCA, internal CA and bifurcation will capture consequently more precisely the general state of the vessel and reflect a more accurate cIMT [5,6]. Point (b): From the methodological description provided by the authors [1] it appears that cIMT measurement was not synchronized with the cardiac cycle (i.e., the end-diastolic phase) as it is recommended [2,7]. If no cardiac synchronization occurred very likely measurements occurred randomly in both cardiac phases and caused a major measurement bias, rendering the measures not solely between the subjects incomparable, but also for the very same subject (e.g., right cIMT evaluation in systole, while left cIMT evaluation in diastole); an average difference of cIMT of 0.041 mm between peak-systole and end-diastole was reported [7].
In conclusion, if cIMT is applied as surrogate marker, we have first to recall the most critical and fundamental issue, namely that cIMT values are expressed in the submillimetric range (e.g., cutoff 600 μm); consequently: (a) a meticulous measurement protocol needs to be in place and (b) high precision measurements by well-trained operators need to be applied. Furthermore, and in respect of the rigor of scientific reporting, the limitations of cIMT as surrogate marker and the pro and cons of the different measurement protocols need mentioning, to allow the reader for a full and balanced evaluation of the results. Given these multiple methodological issues in cIMT evaluation, the cIMT data and the related conclusions of this study 1) should be analyzed with due caution.
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Conflicts of interest
No potential conflict of interest relevant to this article was reported.