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Assessing vascular aging in young subjects with obesity: Usefulness and critical issues

  • Paolo Magni
    Correspondence
    Department of Pharmacological and Biomolecular Sciences, Universita’ degli Studi di Milano, 20133, Milan, Italy.
    Affiliations
    Department of Pharmacological and Biomolecular Sciences, Universita’ degli Studi di Milano, 20133, Milan, Italy
    IRCCS MultiMedica, Sesto San Giovanni, 20099, Milan, Italy
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      Keywords

      The assessment of carotid atherosclerosis markers is a valuable and established “best practice” in adults with several different conditions related to atherosclerotic cardiovascular disease (ASCVD). In particular, carotid intima-media thickness (CIMT), the thickness of the intimal and medial layer of the carotid artery wall, can be measured noninvasively by ultrasound imaging and is considered a marker for the early stage of arterial injury [
      • Libby P.
      • Ridker P.M.
      • Hansson G.K.
      Progress and challenges in translating the biology of atherosclerosis.
      ]. Moreover, CIMT progression has been shown to predict cardiovascular events in the general population, thus also having a prognostic value [
      • Lorenz M.W.
      • Polak J.F.
      • Kavousi M.
      • et al.
      Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data.
      ]. The presence of subclinical carotid plaques, in addition, is associated with higher risk of acute myocardial infarction depending on plaque size and stenosis [
      • Salonen J.T.
      • Salonen R.
      Ultrasonographically assessed carotid morphology and the risk of coronary heart disease.
      ]. Carotid stiffness (CS), evaluated by different parameters (distensibility coefficient, stiffness index β, Young's elastic modulus, Peterson's elastic modulus), is another important marker of arterial damage. Carotid imaging through non-invasive sonography may ultimately allow to collect relevant information for individual cardiovascular risk stratification in the general population [
      • Olmastroni E.
      • Baragetti A.
      • Casula M.
      • et al.
      Multilevel models to estimate carotid intima-media thickness curves for individual cardiovascular risk evaluation.
      ], as well as in high ASCVD risk patients [
      • Georgiopoulos G.
      • Mavraganis G.
      • Delialis D.
      • et al.
      Carotid ultrasonography improves residual risk stratification in guidelines-defined high cardiovascular risk patients.
      ], thereby contributing to precision medicine approaches in the cardiovascular field [
      • Usova E.I.
      • Alieva A.S.
      • Yakovlev A.N.
      • et al.
      Integrative analysis of multi-omics and genetic approaches-A new level in atherosclerotic cardiovascular risk prediction.
      ].
      Since arterial damage and atherosclerosis may begin at an early age in some conditions at greater ASCVD risk, like familial hypercholesterolemia (FH), the implementation of such carotid imaging techniques has appeared useful also in children affected by this genetic condition [
      • Narverud I.
      • Retterstøl K.
      • Iversen P.O.
      • et al.
      Markers of atherosclerotic development in children with familial hypercholesterolemia: a literature review.
      ,
      • Koeijvoets K.C.
      • Rodenburg J.
      • Hutten B.A.
      • et al.
      Low-density lipoprotein receptor genotype and response to pravastatin in children with familial hypercholesterolemia: substudy of an intima-media thickness trial.
      ]. Children with heterozygous FH were actually shown to have a significantly greater CIMT than normal subjects, with a significant deviation starting at age 12, and with greater impact on boys than girls [
      • Wiegman A.
      • de Groot E.
      • Hutten B.A.
      • et al.
      Arterial intima-media thickness in children heterozygous for familial hypercholesterolaemia.
      ]. Another pathological condition associated with greater ASCVD risk is obesity, which has currently epidemic proportions worldwide [
      • Jaacks L.M.
      • Vandevijvere S.
      • Pan A.
      • et al.
      The obesity transition: stages of the global epidemic.
      ]. In adults, obesity has been related to higher CIMT, also as a function of plasma leptin:adiponectin ratio [
      • Norata G.D.
      • Raselli S.
      • Grigore L.
      • et al.
      Leptin:adiponectin ratio is an independent predictor of intima media thickness of the common carotid artery.
      ] and of epicardial adipose tissue [
      • Baragetti A.
      • Pisano G.
      • Bertelli C.
      • et al.
      ,
      • Fracanzani A.L.
      • Pisano G.
      • Consonni D.
      • et al.
      Epicardial adipose tissue (EAT) thickness is associated with cardiovascular and liver damage in nonalcoholic fatty liver disease.
      ]. Today, childhood obesity represents a relevant public health problem in several countries and regions, including Europe [
      • Sares-Jäske L.
      • Grönqvist A.
      • Mäki P.
      • et al.
      Family socioeconomic status and childhood adiposity in Europe - a scoping review.
      ], and is associated with an earlier occurrence of different comorbidities, like type 2 diabetes mellitus and a greater ASCVD risk later in life [
      • Kindblom J.M.
      • Bygdell M.
      • Hjelmgren O.
      • et al.
      Pubertal body mass index change is associated with adult coronary atherosclerosis and acute coronary events in men.
      ]. Based on these considerations, the specific evaluation of carotid markers such as CIMT and CS in children with obesity may offer important information on their vascular status and this is examined in the paper published by Büschges et al. in this issue of Atherosclerosis [

      Buschges, J, Schaffrath, et al., Vascular aging in the young: new carotid stiffness centiles and association with general and abdominal obesity - the KIGGS cohort, Atherosclerosis, in press, 10.1016/j.atherosclerosis.2022.05.003.

      ]. A relevant knowledge gap in this field is the development of accurate CIMT and CS centiles in young subjects, to be then utilized in association with obesity markers, such as body mass index, waist circumference, waist-to-height-ratio, fat and fat-free mass measurement by bioimpedance, subscapular skinfold thickness and blood pressure. The paper reports the results of the 11-year follow-up of the KiGGS cohort, which included sonographic CIMT and CS measurements in 4709 participants (age 14–28 years). Interestingly, CS was found to increase with age in both sexes, with males showing stiffer arteries than females. All obesity parameters at baseline and follow-up, except subscapular skinfold thickness, were positively associated with several CS parameters with moderate relative risks. The Authors conclude that these new CS percentiles show a consistent association of obesity with CS in young subjects.
      This study gives an important contribution to a rather neglected area of research, since the evidence for an association between obesity and increased CIMT and CS in the younger subjects has often been limited by methodological challenges related to the young age of the study populations, methods of percentile derivation and comprehensiveness of the investigated obesity markers. Another open issue is the appropriate age at which starting carotid imaging studies [
      • Dalla Pozza R.
      • Ehringer-Schetitska D.
      • Fritsch P.
      • et al.
      Intima media thickness measurement in children: a statement from the association for European paediatric cardiology (aepc) working group on cardiovascular prevention endorsed by the association for European paediatric cardiology.
      ], which may be standardized around 10–12 years, although some drug interventional studies started earlier, around age 6. This study then highlights that carotid imaging in children and adolescents with obesity offers important information regarding early subclinical atherosclerosis and vascular damage, and emphasizes the crucial role of early cardiovascular prevention.

      Declaration of competing interest

      The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

      Acknowledgements

      The work of Paolo Magni is supported by the Universita’ degli Studi di Milano (Milan, Italy) .

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