**1. Introduction**

Childhood overweight or obesity have beenshown to be associated with an increase in the prevalence of cardiovascular risk factors (CRFs), cardiovascular (CV) risk and development of CV and metabolic diseases later in life [1–3]. This, together with the observed increase in the prevalence of obesity during childhood has led to an increased interest in knowing the factors associated with increased adiposity gain and the link between adiposity gain in early life-stages and future CV alterations; fundamental steps to enable the development of adequate prevention, control and/or treatment strategies. Several studies have been carried out in children and adolescents mainly with the aim of analyzing the association between hemodynamic or arterial characteristics in childhood or adolescence and: (1) body size at birth, (2) growth-related increases in body weight (BW), height (BH), BW-for-BH (BWH), and/or body mass index (BMI), and/or (3) body size at the time of CV evaluation. Results have been heterogeneous. Up to now the factors associated with body size gain as well as the mechanisms underlying the association (impact) of body characteristics and their growth-related changes with CV parameters are not fully known. The controversial findings and lack of a clear understanding of the problem could be attributed to its inherent complexity (e.g., age-related di fferential impact of body size gain, interaction among co-factors, dependence on prior anthropometric conditions), as well as to characteristics and di fferences between studies designed to address it (e.g., methodological approaches, publication bias, statistical analyses) [4–6].

Early accelerated BW gain (e.g., defined as an increase in BW-for-age z-score of at least 0.67 units between 0 and 2 years old (y)) would be associated with detrimental CV changes in children and adolescents [7,8]. In this regard, at least five interrelated issues should be clarified. First, the strength of the association between CV characteristics (i.e., hemodynamic and arterial) and anthropometric changes (e.g., early BW gain), along with their independence from birth weight and current body conditions.An association between low birth weight (LBW) and CV alterationshas been described, which would be reinforced by (or could even depend on) an accelerated BW gain in the postnatal period and/or by associated excessive subsequent adipose gain expressed by an elevated BMI at the time of CV evaluation [9]. Second, the magnitude of the interactions of anthropometric and CV parameters respect to body size at birth and current BMI should be addressed [10]. Third, the association between BW gain and CV parameters should be analyzed considering that it may depend on the timing of growth-related body changes (e.g., acceleration) [7,8] and/or on thesubject'sage (i.e., at the time of CVassessment) [6,11]. Fourth, as previous works reported that early growthpatterns could be associated with the development or exposure to factors associated with increased CV risk (CRFs' clustering) [12], the real (independent) clinical meaning or CV impact of BW gain should be determined, taking into account the exposure to CRFs. Fifth, the association between body size gain, birth-size and/or current anthropometric conditions with hemodynamic or arterial parameters could vary, depending on the: (a) arterial type (e.g., muscular vs. elastic); (b) site of evaluation and hemodynamic parameters considered (e.g., peripheral vs. central); and (c) arterial pathway considered (e.g., conductance vs. resistance) [13,14]. Recently, our group demonstrated that z-BMI variations in children and adolescents are positively associated with peripheral (brachial) and central (aortic) blood pressure levels (pBP and cBP, respectively); carotid, femoral and brachial artery diameters; carotid (but not femoral or brachial) intima-media thickness (IMT); arterial sti ffness and sti ffness gradient. Moreover, we found a "hierarchical order" among hemodynamic and arterial variations associated with z-BMI. pBP was the variable with the greatest variations associated with z-BMI (particularly pBP rather than cBP was associated with z-BMI). The sti ffness of central (but not peripheral) arteries was associated with z-BMI (a pBP-dependent association). In turn, variations in arterial diameters were associated with z-BMI, without di fferences between the elastic and muscular arteries [13]. The above highlights the importance of a comprehensive, multiparametric approach when evaluating the CV system. If results obtained in an arterial segmen<sup>t</sup> and/or for a given parameter were generalized, significant errors (biases) could be made.

This work's aims were: (1) to evaluate and compare the strength of association between hemodynamic and arterial characteristics and (a) anthropometric data at specific growth stages (e.g., birth, 6 y, 18 y) and (b) body size changes during early (e.g., 0–2 y), intermediate (0–6 y), late (6–18 y) and global (0–18 y) growth; (2) to determine whether the association between CV characteristics and growth-related body size changes depends on size at birth and/or at the time of CV evaluation; and (3) to analyze the explanatory capacity of growth-related body size changes for hemodynamic and arterial characteristics in early childhood (6 y) and at the beginning of adulthood (18 y), before and after adjusting for body-size at birth, current BMI and/or exposure to CRFs.

#### **2. Materials and Methods**
