The Association between Premature Adrenarche and Cardiovascular Risk May Be Greater than Expected

Abstract

Aim: The aim of this study was to investigate the cardiovascular risk of children with premature adrenarche (PA). Methods: A total of 75 children (44 with PA and 31 control subjects) aged 6-10 years were included in the study. Their metabolic, anthropometric, and echocardiographic parameters were recorded and compared. Results: Triglyceride, DHEA-SO₄, and 17-hydroxyprogesterone levels were significantly higher in the PA group (p = 0.04, p = 0.002, and p = 0.01, respectively). The echocardiographic assessments revealed that the left ventricular end-diastolic diameter (LVEDD) (p < 0.001), left ventricle (LV) and right ventricle (RV) ejection times (p = 0.031 and p = 0.035, respectively), and LV and RV Tei index measurements (p = 0.033 and p = 0.006, respectively) were significantly higher in the PA group than in the control group, whereas the E/e' ratio of the mitral lateral annulus was significantly lower in the PA group (p = 0.006). Additionally, carotid intima-media thickness and epicardial adipose tissue measurements were significantly increased in the PA group compared to the control group (p < 0.001). Conclusion: Early atherosclerotic changes and subclinical impairment of cardiac function were observed in children with PA. It is possible that these children are on a course for early cardiovascular disease.

Challenges in the Cross-Sectional Assessment of Cardiovascular Risk in Children with Premature Adrenarche due to the Multifaceted Nature of Atherosclerosis

“…One potential explanation for the differences the authors report in the study regarding echocardiography and vascular ultrasound findings could be the differences in stature between children with PA and controls, since it is established that children with PA are taller than their peers owing to advanced bone age. Stature-based adjustment of the imaging findings would probably diminish the statistical significance of the differences that Çelik et al [1] report, although, surprisingly, the differences in stature between children with PA and controls were not statistically significant in their study. Stature-, gender-, and age-adjusted normative data of vascular ultrasound findings such as carotid intima-media thickness have been published recently [10].…”

“…In the absence of dyslipidemia and insulin resistance, elevated androgens per se cannot be linked to increased CVR. The correlations Çelik et al [1] report in their study may probably be attributable to a confounding factor such as age. We have recently documented that girls with PA born appropriate for gestational age had reduced atherogenic indices when compared to age- and body mass index-matched controls [9], where the athero­genic index was calculated by applying the following formula: atherogenic index = triglycerides/high-density lipoprotein cholesterol.…”

“…With interest I read the study by Çelik et al [1] recently published in Hormone Research in Paediatrics on the assessment of cardiovascular risk (CVR) in children with premature adrenarche (PA). While I appreciate the authors’ endeavor to perform an extensive investigation of the subjects with echocardiography and vascular ultrasound, several important points may warrant reconsideration.…”

“…Estrogens inhibit monocyte endothelial adhesion and endothelial cell expression of several adhesion molecules [8], which are necessary initial steps in atherosclerosis. In the study by Çelik et al [1], data from boys and girls with PA were evaluated together with respect to metabolic parameters and CVR, which may constitute a caveat in accurate interpretation of the findings owing to the gender-related differences in the expression of androgen receptors in macrophages [7]. Moreover, the absence of significant differences between the children with PA and controls with respect to plasma lipids and insulin resistance argues against CVR in children with PA. Çelik et al [1] also report correlations of serum DHEAS levels with carotid intima-media thickness and epicardial adipose tissue thickness, which are not in line with the aforementioned physiological facts on the genesis of atherosclerosis.…”

“…Given the well-established facts in the evolution of atherosclerosis, the study cohort of Çelik et al [1] did not have dyslipidemia, a history of low birth weight, or hyperinsulinemia as potential culprits for an increased CVR in children with PA. In addition, the authors did not provide data regarding the family history of coronary arterial disease in the subjects.…”