Blood pressure and arterial stiffness in obese children and adolescents.

Obesity, elevated blood pressure (BP) and arterial stiffness are risk factors for cardiovascular disease. A strong relationship exists between obesity and elevated BP in both children and adults. Obesity and elevated BP in childhood track into adult life increasing the risk of cardiovascular disease in adulthood. Ambulatory BP is the most precise measure to evaluate the BP burden, whereas carotid-femoral pulse wave velocity (cfPWV) is regarded as the gold standard for evaluating arterial (i.e. aortic) stiffness. These measures might contribute to a better understanding of obesity's adverse impact on the cardiovascular system, and ultimately a better prevention and treatment of childhood obesity. The overall aim of the present PhD thesis is to investigate arterial stiffness and 24-hour BP in obese children and adolescents, and evaluate whether these measures are influenced by weight reduction. The present PhD thesis is based on four scientific papers.  In a cross-sectional design, 104 severe obese children and adolescents with an age of 10-18 years were recruited when newly referred to the Children's Obesity Clinic, Holbæk University Hospital, and compared to 50 normal weighted age and gender matched control individuals. Ambulatory BP was measured, and cfPWV was investigated in two ways in respect to the distance measure of aorta; the previously recommended length - the so called subtracted distance, and the currently recommended length - the direct distance. In a longitudinal design, the obese patients were re-investigated after one-year of lifestyle intervention at the Children's Obesity Clinic in purpose of reducing the degree of obesity. In the cross-sectional design, the obese group had higher measures of obesity, while matched for age, gender and height, when compared to the control group. In the longitudinal design, 74% of the 72 followed up obese patients experienced a significant weight reduction. CfPWV was dependent on the method used to measure the length of the aorta. The subtracted distance was not consistent in its relation to height in the obese and the control group. Opposite, the direct distance was consistent in its relation to height in the two groups. Therefore, cfPWV using the direct distance (cfPWV-direct) was regarded as the appropriate measure of arterial stiffness. CfPWV-direct was reduced in the obese group after adjustment for known confounders. In the longitudinal design, weight reduction across one year did not have an impact on cfPWV-direct in the obese patients. In fact, cfPWV-direct was higher at follow-up, which was explained by the increased age and partly by changes in BP and heart rate. The obese group had a relatively higher night- than day-time BP when compared to the control group. The obesity-related elevated night-time BP was independent of arterial stiffness and insulin resistance. Although night-time systolic BP was related to arterial stiffness and tended to be related to insulin resistance, insulin resistance and arterial stiffness were not related. In the longitudinal design, changes in anthropometric obesity measures across one year were associated with changes in 24-hour, day- and night-time BP, and consistent when evaluated in standardised values that accounted for growth. No association was found between changes in anthropometric obesity measures and changes in clinic BP. In conclusion, the results suggest that obesity in children is not "yet" associated with structural changes in aorta when evaluated with the appropriate new method of cfPWV. In this respect, weight reduction did not have an impact on arterial stiffness. The ambulatory BP, namely the night-time BP, was elevated in the obese patients, whereas changes in anthropometric obesity measures were related to changes in ambulatory BP but not to changes in clinic BP. In perspective, it is reassuring that weight changes are accompanied with a change in 24-hour BP as ambulatory BP is the most precise measure to evaluate the BP burden, and it emphasises the use of 24-hour ambulatory BP measurements in children and adolescents. It is important to recognise, that obese children who recover their normal weight before adulthood will have a similar cardiovascular risk as those who were never obese. Hence, early treatment and prevention of childhood obesity is important because it may prevent irreversible damage to the cardiovascular system.