Preclinical atherosclerosis and asthma

Dear Editor,

Winder and colleagues published in the January 2022 issue of the BMC an article titled, “The association of allergic asthma and carotid intima-media thickness in adolescence: data of the prospective early vascular ageing (EVA)-Tyrol cohort study”, investigating the relationship between asthma and cardiovascular risk factors (CVRF) [1]. The authors write, “In recent years, evidence has accumulated that asthma is associated with cardiovascular disease (CVD). …Given the important role of inflammatory processes and the immune system in human atherogenesis, it is plausible that subjects suffering from chronic inflammation—a hallmark characteristic of asthma—are more prone to CVD” [1]. To investigate this potential relationship, the authors used the carotid artery intima-media thickness (cIMT) as an ultrasonographic surrogate marker of pre-clinical atherosclerosis. In their community-based, non-randomized controlled trial involving 1,506 subjects with a mean age of 17.8 years (standard deviation: 0.90), 58 subjects (3.9%) had allergic asthma, 268 subjects (17.8%) had a physician-diagnosed inhalant allergy, 22 subjects (1.5%) had non-allergic asthma, and 1,158 subjects (76.8%) had no asthma or inhalant allergies. The measurement of the cIMT occurred on the distal wall of the common carotid arteries (CCA) by high-resolution ultrasound. The authors write, “Three representative measurements in longitudinal images on the distal 4 cm on both sides were done on digitally stored images by a single rater, experienced in ultrasound techniques without information on clinical characteristics of the participant. The mean from all six measurements was used for the present analysis (cIMT_MEAN)”. Subjects with non-allergic asthma (411.7 vs. 411.7 μm; p = 0.932) or inhalant allergy (420.0 vs. 411.7 μm; p = 0.118) did not have significantly higher carotid intima-media thickness (cIMT) compared to healthy controls. However, subjects “with allergic asthma had significantly higher cIMT (430.8 vs. 411.7 μm; p = 0.004) compared to those without and this association remained significant after multivariable adjustment for established cardiovascular risk factors”. The authors concluded, “our analysis revealed significant associations between allergic asthma and increased cIMT in adolescents. Physicians should therefore be aware of allergic asthma as a potential CVRF in children and adolescents”. Some comments are needed to evaluate the results and conclusions of the authors in a more balanced way. Winder et al. measured the cIMT only at the distal wall of the CCA [1]. A single location cIMT measurement can coincide with a normal carotid artery (CA) segment, while missing atherosclerotic vessel sections, given the asymmetric presentation of atherosclerosis. A composite cIMT measurement, including several sections of the CA tree (e.g. including proximal/distal walls of the CCA, bifurcation and the internal CA) reflects more accurately the actual cIMT than a single location measurement and represents a better predictor for CVD than a single location measurement [2]. A further aspect to consider, to obtain accurate measurements, is to synchronize cIMT measurement with the cardiac cycle as cIMT varies during the cardiac cycle [3] given vessel diameter changes in the two cardiac phases. Winder et al. did not specify if cIMT was synchronized with the cardiac cycle [1]; therefore, the differences in cIMT between the two groups can be due to measurements that occurred during different cardiac cycles. Although there is no consensus within the community as to cut-off values for pathologically increased cIMT, there is a consensus that a cIMT less than 600 μm is normal [4]. The mean cIMT (430.8 μm) in the asthma group by Winder et al. [1] falls still and largely within the normal range of cIMT and has consequently no diagnostic or prognostic value. There is a need for standardization of cIMT measurements among different age groups. Winder et al.’s conclusion that “Physicians should therefore be aware of allergic asthma as a potential CVRF in children and adolescents” [1], should be analyzed within the above-mentioned limitations of the applied methodology.