CIMT may not be a marker for sub-clinical atherosclerosis in the young, ALSPAC study.

Greater carotid intimal medial thickness (cIMT) is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood. In the recent ALSPAC study published in JACC, Cheisa et al have shown that subtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis.

Lifetime management of cardiovascular disease (CVD) risk factors is recognized as an important strategy for reducing future population burden of disease. Increased cIMT is a well-established marker for future adverse CVD outcomes in older populations and is frequently also used in young population cohorts to link emerging CVD risk factors to the earliest development of subclinical atherosclerosis. But the major limitation of cIMT is that whether an increase is due to intimal hyperplasia (reflecting atherosclerosis) or medial hypertrophy (reflecting remodelling changes) is not distinctly identified. Ultra-high frequency ultrasound technology (UHFUS) now permits the individual layers of the arterial wall to be studied in detail and can thus aid in differentiating the aforementioned changes.

In the ALSPAC study, associations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences.

Fat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT, whereas fat mass was negatively associated with cIMT. Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor−associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor.

cIMT is a well-established risk marker for atherosclerosis and although its use is not recommended in clinical guidelines for risk stratification―has been shown to predict future cardiovascular events independently of traditional risk factors in adults. Increases in FFM in the present study were found to be positively associated with both carotid lumen diameter and cIMT, which resulted in the maintenance of the IMT/lumen ratio and a preservation of vessel CWS when increases in body mass consisted of lean tissues.

This suggested that subtle changes in cIMT in young healthy populations appear to be confined to the medial layer and may predominantly represent physiological adaptation to differing levels of FFM mass rather than evidence of intimal disease and signs of early subclinical atherosclerosis.

"These findings are derived from a young and healthy population cohort free from established clinical disease. Additional studies are needed to establish whether the evolution of cIMT differs in individuals with differing risk factor profiles (e.g., young people with diabetes, familial hypercholesterolemia, and so on). Until such time, increases in cIMT should be interpreted with caution before adulthood", concluded the authors.

Source: JACC imaging: J Am Coll Cardiol Cardiovasc Imaging. 2021 Feb, 14 (2) 468–478