Carotid intima-media thickness, primary aldosteronism, and target organ damage in untreated hypertensive patients

Dear Sir,

Li et al. investigated in their study the association between primary aldosteronism (PA) and target organ damage (TOD) among patients with newly diagnosed hypertension.¹ The authors wrote, “Clinical studies have shown that PA is associated with an increased risk of TOD, including left ventricular hypertrophy (LVH), microalbuminuria and increased carotid intima-media thickness (CIMT), compared with essential hypertension (EH)”.¹ Fifty-seven patients with PA (mean age 44 years, 56% male gender) and 987 individuals (matched for age/gender) without PA were included.¹ As surrogate marker for preclinical atherosclerosis the CIMT was used.¹ The authors concluded that their research demonstrated “that individuals with PA had more severe TOD than those without PA, including LVH, carotid atherosclerosis, and microalbuminuria”.¹

Some comments are needed to evaluate the results and conclusions of this study in a more exhaustive way. As to their measurement, the authors wrote, “the vertical distance from the upper margin of vascular intima to the upper margin of the vascular adventitia of the distal common carotid artery (with an up–and–down range of 1.0 to 1.5 cm below the level of the bifurcation) or the initial segment of the internal carotid artery was measured as the intima-media thickness (IMT)”.¹ From the methodological description, namely the use of the word “or”, it appears that the authors measured not uniformly in (a) preestablished carotid artery (CA) segment(s) (e.g., common carotid artery (CCA) and internal carotid artery (ICA), CCA solely, ICA solely), but apparently chose for each subject a different segment of the CA, that is, the CCA or the ICA. Ultrasonography cannot differentiate intermediate stages between IMT and atherosclerotic plaque, whereby such conditions, while occasionally present at the CCA, are common at the bifurcation and the ICA.⁴ In the “Mannheim Carotid Intima-Media Thickness and Plaque Consensus paper” the important differentiation between IMT and plaque formation is made, “Epidemiological and intervention studies have shown that although both share common risk factors of atherosclerosis, its natural history, patterns of risk factors and the prediction of cardiac and cerebral events are different for carotid IMT and carotid plaque”.⁴ Ling et al., wrote in their meta-analysis, “CCA-IMT is more likely linked to systemic atherosclerosis and vascular remodeling in response to hemodynamic changes rather than ICA-IMT, which is related to localized atherosclerosis”.² It is not comprehensible why Li et al.¹ did not perform uniformly their CIMT measures at the same CA location(s) and instead adopted a highly heterogenic data acquisition. As to their selected cutoff, Li et al. wrote, “CIMT was defined as the mean of the bilateral IMT. CIMT < 1.0 mm was classified as normal, and 1.0 mm ≦ CIMT ≦ 1.5 mm was classified as CIMT thickening”.¹ Cutoff values in CIMT based studies are a problematic and controversial issue. Liao et al.³ wrote in their excellent paper, “Normative values for carotid intima-media thickness and its progression: Are they transferrable outside of their cohort of origin?” following “The distribution of CIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location, and ultrasound protocol”. As the smallest inaccuracies (at the sub-millimetric level) suffice to categorize subjects into different CIMT categories and given the unresolved debate regards CIMT cut-off values, the author of this letter suggests avoiding cutoffs and to indicate rather reference ranges (to allow also to account for a margin of error) without risking misclassifying immediately subjects.

A further critical point in CIMT acquisition that needs mentioning is if acquisitions were synchronized, as recommended, with the diastolic cardiac phase.⁴ CIMT values change during the cardiac cycle due to lumen-diameter variations, being thickest at end-diastole (ED) and thinnest at peak systole (PS).^{4, 5} If no synchronization occurred it is possible that Li et al.¹ measured inadvertently (randomly) in both cardiac phases, rendering uneven their measurements and potentially incomparable between the subjects of their cohort.. Li et al.¹ did not report further if the CIMT data acquisition was performed by one sole or multiple operators. Bauer et al. detailed this important aspect, “The interobserver variability of maximum CIMT in the CCA was found to be 0.14 ± 0.16 mm and 0.13 ± 011 mm for mean CIMT. The interobserver variability is reported to be slightly higher (0.20 ± 0.26 mm and 0.18 ± 0.24 mm, respectively)”.⁶

In summary: The CIMT results and the conclusion “that individuals with PA had more severe TOD than those without PA, including…carotid atherosclerosis …¹” should be considered with caution, within the context of the above-mentioned limitations of CIMT application.

Christian Saleh wrote and revised the manuscript.

The author declares no conflicts of interest.