Establishing reference values for macro- and microvascular measurements in 4-to-5 year-old children of the ENVIRONAGE prospective birth cohort

Abstract

Cardiovascular risk factors are usually better tolerated, and can therefore be perceived as less harmful, at a young age. However, over time the effects of these adverse factors may persist or accumulate and lead to excess morbidity and mortality from cardiovascular diseases later in life. Until now, reference values for the basic cardiovascular health characteristics of 4-to-6 year-old children are lacking. Within a follow-up study of the ENVIRONAGE (ENVIRonmental influence ON early AGE) birth cohort we assessed various cardiovascular measurements in 288 children aged 4-5 years. For the macrovasculature, we measured their blood pressure and examined the intima-media thickness of the carotid artery (CIMT), the arterial elasticity (including the pulse-wave velocity (PWV), carotid distensibility (DC) and compliance (CC) coefficients), the carotid beta stiffness index (SI beta) and Young's Elastic Modulus (YEM). Retinal microvascular traits included the Central Retinal Arteriolar Equivalent (CRAE) and Central Retinal Venular Equivalent (CRVE). Age of the study population averaged (+/- SD) 4.2 (+/- 0.4 years. Mean systolic and diastolic blood pressure were 97.9 (+/- 8.1) mmHg and 54.7(+/- 7.6) mmHg, respectively. CIMT for the total population averaged 487.1 (+/- 68.1) mu m. The average stiffness values for DC, CC, SI beta, and PWV were 78.7 (+/- 34.2) 10-(3)/kPa, 1.61 (+/- 0.59) mm(2)/kPa and 4.4 (+/- 2.4), and 3.7 m/s (+/- 0.9) respectively. The mean determined for YEM was 163.2 kPa (+/- 79.9). Concerning the microvasculature, the average CRAE was 180.9 (+/- 14.2) mu m and the corresponding value for CRVE was 251.0 (+/- 19.7) mu m. In contrast to the macrovasculature, a significant gender-related difference existed for the microvasculature: in boys, both the CRAE (178.8 mu m vs 182.6 mu m; p = 0.03) and CRVE (247.9 mu m vs 254.0 mu m; p = 0.01) were narrower than in girls. We have provided reference values for young children to understand changes in the early cardiovascular health trajectory. Establishing these reference values of cardiovascular phenotypes at this young age is necessary to develop targeted health promotion strategies as well as for better understanding of the life course changes of both small and large blood vessels.