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

doi:10.1016/j.atherosclerosis.2014.12.029

Atherosclerosis

Volume 238, Issue 2, February 2015, Pages 380-387

https://doi.org/10.1016/j.atherosclerosis.2014.12.029 Get rights and content

Highlights

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Intima-Media-Thickness (IMT) in childhood provides information on vascular damage.
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Different measurement procotols impede comparison of IMT values of different centers up to now.
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AEPC recommends to adhere to these guidelines to strengthen the predictive value of IMT measurement.
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Future imaging will include dynamic and structural IMT measurement.

Abstract

Atherosclerosis causing cardiovascular disease is the most common cause of death in the developed world. Early precursors of vascular changes – subclinical atherosclerosis – warrant special attention as this process can be stabilized or even reversed if treated in time. Sonographic Intima Media Thickness measurement of the carotid artery (cIMT: carotid Intima-Media-Thickness) is considered a valid surrogate marker for cardiovascular risk allowing assessment of atherosclerotic changes at a very early stage. It is easy to apply due to its non-invasive character. Moreover, cIMT has been proven to provide reliable and reproducible results both in adult and adolescent patients. For the paediatric age group, several characteristics deserve special consideration. The heterogeneity of techniques of scanning, measurement and interpretation impede the comparison and interpretation of IMT values so far. Also, age- and sex-dependent normative data have to be considered for interpretation. Thus, the Association for European Paediatric Cardiology (AEPC) Working Group on Cardiovascular Prevention concludes to refer a statement on cIMT scanning, measurement and interpretation with special focus on paediatric patients. This statement includes an overview on normative data available as well as a practical guideline for the setting, scanning, measurement and interpretation of IMT values. Synchronizing different measurement methods will allow for comparing the results of several research centers. By that, in a large patient number, sufficient information may be given to assess the long-term endpoints of cardiovascular morbidity and mortality.

Introduction

Atherosclerosis starts in childhood leading to cardiovascular disease in the adult patient [1], [2]. Thus, early recognition of vascular changes to prevent cardiovascular sequelae is warranted [3]. One of the most commonly used non-invasive diagnostic methods is measurement of the Intima-Media-Thickness of the common carotid artery by ultrasound. Following the initial consideration as a surrogate marker for atherosclerosis (cIMT: carotid Intima-Media-Thickness), recent meta-analyses raised questions about the usefulness for the assessment of the vascular status in adult patients. Moreover, including carotid plaque screening seems to add valuable informations for the prediction of cardiovascular events more than IMT measurement alone in the adult patient [4], [5], [6]. In children, several issues have to be considered. For example, patient preparation and technical equipment deserve special attention. Also, cIMT values have to be compared to age and sex-specific normative data. Thus, the Association for European Paediatric Cardiology (AEPC) Working Group on Cardiovascular Prevention suggests harmonising the cIMT acquisition and measurement methods and proposes a standardized examination protocol, which will be presented in the following.

Section snippets

Background

Starting from 1986, the sonographic evaluation of Intimal-Medial-Thickening of the common carotid arteries has gained scientific and clinical significance [7]. In past years, cIMT measurement has been considered a surrogate marker of atherosclerosis [8]. Moreover, it seemed to be useful for the prediction of clinical cardiovascular events. Recent meta-analyses, however, concluded that IMT measurement alone could not predict cardiovascular events and showed that including carotid plaque

Patient selection

In adult patients, cIMT measurement reflects the single patient's vascular status. It seems wise to include in cIMT measurement programs all those paediatric patients at elevated cardiovascular risk [1], [3]. Following the definition of the American Heart Association Expert Panel on Population and Prevention Science, paediatric patients with elevated cardiovascular risk can be divided into three groups [1]. Patients with high cardiovascular risk are patients with homozygous familial

Limitations

Although the cIMT measurement is widely used and – due to its non-invasive character – can be applied easily in the outpatient setting, the overall advantage of early recognition of increased cIMT has to be proven so far. Several studies have addressed the usefulness of preventive strategies in reducing increased cIMT values [11], [27]. As the cIMT is considered a surrogate marker for atherosclerosis, a reduction in cIMT should indicate also a reduced risk for atherosclerosis. In adult

Summary and outlook

cIMT scanning and measurement offers noteworthy information about the cardiovascular risk if performed according to the requirements outlined in the present statement. Also for children, the cIMT may provide a reliable surrogate marker for vascular health. Considering the progression of vascular changes throughout live, it seems prudent to detect subclinical signs of arterial damage and atherosclerosis very early and relief atherosclerotic burden by preventive measures. Thus, especially in the

Conflict of interests

R. Dalla Pozza: None.

D. Ehringer-Schetitska: None.

P. Fritsch: None.

E. Jokinen: None.

A. Petropoulos: None.

R. Oberhoffer: None.

Acknowledgement

The authors want to appreciate the great contribution of J. Elmenhorst, B. Böhm and H. Weberruß (literature research); of V. Herceg-Cavrak (manuscript edition), and of R. Meijer, M. Bots and J. Stein (extern reviewers).

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The first critical issue is to characterize in children aged 2–5 years, those CV risk factors/clinical conditions associated with dramatically accelerated atherosclerosis. Presence of clinical conditions such as obesity, diabetes mellitus, Kawasaki disease, etc., or positive family history for premature CV disease should be evaluated. Subsequently, a complete lipid profile and Lipoprotein(a) determination are recommended for children with increased baseline CV risk. Individuals with altered lipid profile could then undergo genetic testing for monogenic dyslipidemias to identify children with high CV genetic risk, who will be directed to appropriate therapeutic options. In perspective, calculation of a polygenic risk score, based on the analysis of several common single-nucleotide polymorphisms, could be integrated for better risk assessment.
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Seventy T1DM patients and diabetic nephropathy were enrolled with a mean age 15.2 ± 1.96 years and median disease duration 7 years. Patients were randomly assigned into two groups; intervention group which received oral omega-3 fatty acids capsules (1 g daily). The other group received a matching placebo and served as a control group. Both groups were followed-up for 6 months with assessment of fasting blood glucose (FBG), HbA1c, fasting lipids, urinary albumin creatinine ratio (UACR), KIM-1 and CIMT.
After 6 months, omega-3 fatty acids adjuvant therapy for the intervention group resulted in a significant decrease in FBG, HbA1c, triglycerides, total cholesterol, LDL-cholesterol, UACR, KIM-1 and CIMT, whereas, HDL-cholesterol was significantly higher post-therapy compared with baseline levels and compared with the control group (p < 0.05). Baseline KIM-1 levels were positively correlated to HbA1c, UACR and CIMT. Supplementation with omega-3 fatty acids was safe and well-tolerated.
Omega-3 fatty acids as an adjuvant therapy in pediatric T1DM patients with diabetic nephropathy improved glycemic control, dyslipidemia and delayed disease progression and subclinical atherosclerosis among those patients.
This trial was registered under ClinicalTrials.gov Identifier no. NCT05980026.
Fatty acid binding protein 1 (FABP1) and fatty acid binding protein 2 (FABP2) as a link between diabetic nephropathy and subclinical atherosclerosis in children and adolescents with type 1 diabetes
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Diabetic nephropathy is a major cause of morbidity and mortality in type 1 diabetes mellitus (T1DM). Fatty acid binding proteins (FABP1 and FABP2) play a role in the development and progression of chronic kidney disease including type 2 diabetes mellitus.
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Sixty patients with T1DM were divided into 2 groups according to the presence of nephropathy and compared with 30 healthy controls. CIMT, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), urinary albumin creatinine ratio (UACR), fasting lipid profile and serum FABP1 and FABP2 levels were assessed.
FABP1 and FABP2 levels were significantly higher among type 1 diabetic patient with and without nephropathy compared with healthy controls with the highest levels among patients with nephropathy (p < 0.001). There were significant positive correlations between FABP1 and FABP2 and each of systolic blood pressure, CIMT, FBG, HbA1c and total cholesterol among T1DM patients. FABP1 was negatively correlated to glomerular filtration rate. Multivariable linear regression analysis showed that systolic blood pressure, CIMT, FBG and HbA1c were the significant independent variables related to FABP1 levels in type 1 diabetic patients with nephropathy. ROC curve analysis was performed to determine the cutoff value of FABP1 and FABP2 that could detect nephropathy.
FABP1 and FABP2 levels are elevated in children and adolescents with T1DM and could represent a link between diabetic nephropathy and subclinical atherosclerosis.
Early Life Determinants of Vascular Structure in Fetuses, Infants, Children, and Adolescents: A Systematic Review and Meta-Analysis
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To investigate the association between early life exposures during the first 1000 days (conception to age 24 months) and aortic intima-media thickness (aIMT), an early indicator of cardiovascular disease (CVD) risk, in youths.
The MEDLINE, Embase, Scopus, CINAHL, and Allied and Complementary Medicine databases were searched from inception to July 2021. Eligibility criteria included observational controlled studies in youths aged <20 years with risk factors/exposures during the first 1000 days and aIMT measurements (unadjusted mean ± SD). Outcome data were pooled using a random-effects meta-analysis. Meta-regression was used to investigate confounders.
A total of 8657 articles were identified, of which 34 were included in our meta-analysis. The age of participants ranged from 22.9 weeks gestation in utero to 10.9 years. In the meta-analysis (n = 1220 cases, n = 1997 controls), the following factors were associated with greater aIMT: small for gestational age (SGA) status (14 studies, mean difference, 0.082 mm; 95% CI, 0.051-0.112; P < .001; I² = 97%), intrauterine growth restriction (6 studies; mean difference, 0.198 mm, 95% CI, 0.088-0.309; P < .001; I² = 97%), preeclampsia (2 studies; mean difference, 0.038 mm; 95% CI, 0.024-0.051; P < .001; I² = 38%), and large for gestational age (LGA) status (3 studies; mean difference, 0.089 mm; 95% CI, 0.043-0.0136; P < .001; I² = 93%). In meta-regression, older age (P < .001), higher prevalence of maternal smoking (P = .04), and SGA (P < .001) were associated with greater difference in aIMT in preterm participants compared with controls. Limitations included the high heterogeneity present in most meta-analyses and the scope of our meta-regression.
Adverse early life exposures are associated with greater aIMT in youths, consistent with an increased risk for CVD later in life. Further research is needed to determine whether intervention and preventive strategies deliver clinical benefits to improve future cardiovascular health.
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The cohort consisted of 900 subjects who had aortic-femoral PWV and CIMT measurements. These participants were examined 5-16 times for body mass index (BMI), blood pressure, atherogenic index of plasma (AIP), and low-density lipoprotein cholesterol (LDLC) from childhood to adulthood. The area under the curve (AUC) was calculated as a measure of long-term burden of the risk factors.
Adjusting for covariates, adult PWV was associated with AUCs of BMI, systolic blood pressure (SBP) and AIP (standardized regression coefficient [β] = 0.191, 0.321, 0.153, respectively; P < 0.001 for all). Adult CIMT was associated with AUCs of BMI, SBP, AIP and LDLC (β = 0.115, 0.202, 0.141, 0.152, respectively; P < 0.001 for all). Moreover, childhood BMI was associated with adult PWV and CIMT (β = 0.088 and 0.075, respectively; false discovery rate q values < 0.05 for both), and childhood LDLC with adult CIMT (β = 0.079; false discovery rate q value < 0.05). These associations did not differ significantly among race and sex groups.
The life-course cumulative burden of BMI, SBP, and AIP has common effects on arterial wall stiffening and thickening, whereas LDLC is specifically associated with arterial wall thickness, and this effect starts in early life.
On dispose de peu de données au sujet des effets différentiels et communs des facteurs de risque cardiovasculaire sur les modifications infracliniques de la structure et de la fonction vasculaires. Nous avons cherché à examiner les liens entre le fardeau cumulatif des facteurs de risque cardiovasculaire au cours de la vie, la vitesse de l’onde de pouls (VOP) et l’épaisseur intima-média carotidienne (EIMC) chez l’adulte au sein d’une cohorte longitudinale de la Bogalusa Heart Study.
La cohorte était composée de 900 sujets chez qui la VOP carotidofémorale (VOP aortique) et l’EIMC avaient été mesurées. Ces sujets avaient subi de 5 à 16 examens au cours desquels l’indice de masse corporelle (IMC), la pression artérielle, l’indice d’athérogénicité plasmatique (IAP) et le taux de cholestérol à lipoprotéines de faible densité (cLDL) avaient été mesurés, de l’enfance à l’âge adulte. L’aire sous la courbe (ASC) a été calculée en tant que mesure du fardeau à long terme des facteurs de risque.
Après correction en fonction des covariables, la VOP chez l’adulte a été associée à l’ASC de l’IMC, de la pression artérielle systolique (PAS) et de l’IAP (coefficient de régression normalisé [β] = 0,191, 0,321 et 0,153, respectivement; P < 0,001 dans tous les cas). L’EIMC chez l’adulte a été associée à l’ASC de l’IMC, de la PAS, de l’IAP et du cLDL (β = 0,115, 0,202, 0,141 et 0,152, respectivement; P < 0,001 dans tous les cas). En outre, l’IMC chez l’enfant a été associé à la VOP et à l’EIMC chez l’adulte (β = 0,088 et 0,075, respectivement; taux de fausse découverte [valeur q] < 0,05 dans les deux cas), et le taux de cLDL chez l’enfant a été associé à l’EIMC chez l’adulte (β = 0,079; taux de fausse découverte [valeur q] < 0,05). Ces associations ne présentaient pas de différences interethniques ou intersexuelles significatives.
Le fardeau cumulatif de l’IMC, de la PAS et de l’IAP en cours de vie se traduit par des effets communs sur le durcissement et l’épaississement de la paroi artérielle, tandis que le taux de cLDL est spécifiquement associé à l’épaisseur de la paroi artérielle, et cet effet débute tôt dans la vie.

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ReviewIntima 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

Highlights

Abstract

Introduction

Section snippets

Background

Patient selection

Limitations

Summary and outlook

Conflict of interests

Acknowledgement

Lancet

Atherosclerosis

J Am Coll Cardiol

Lancet

J Am Coll Cardiol

Atherosclerosis

Atherosclerosis

J Am Soc Echocardiogr – Off Publ Am Soc Echocardiogr

Diabetes Res Clin Pract

Atherosclerosis

J Am Coll Cardiol

Ultrasound Med Biol

Lancet

Atherosclerosis

J Am Coll Cardiol

Am J Cardiol

J Pediatr

Am Heart J

Circulation

Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the cardiovascular risk in young finns study

JAMA – J Am Med Assoc

Noninvasive assessment of subclinical atherosclerosis in children and adolescents: recommendations for standard assessment for clinical research: a scientific statement from the american heart association

Hypertension

Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging

Circulation

Measurement of arterial wall thickness as a surrogate marker for atherosclerosis

Circulation

Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis

Circulation

Is carotid intima media thickness useful for individual prediction of cardiovascular risk? Ten-year results from the carotid atherosclerosis progression study (caps)

Eur heart J

Mannheim carotid intima-media thickness consensus (2004–2006). An update on behalf of the advisory board of the 3rd and 4th watching the risk symposium, 13th and 15th european stroke conferences, mannheim, germany, 2004, and brussels, belgium, 2006

Cerebrovasc Dis

Aortic and carotid wall thickness in term small-for-gestational age newborns and relationship with prenatal signs of severity

Ultrasound Obstet Gynecol – Off J Int Soc Ultrasound Obstet Gynecol

Intima-media thickness and flow-mediated dilatation in the helsinki study of very low birth weight adults

Pediatrics

Ultrasound settings significantly alter arterial lumen and wall thickness measurements

Cardiovasc Ultrasound

Review
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