Determinants of the vascular system in the young

Abstract

It is known that the origins of cardiovascular diseases (CVD), one of the major causes of morbidity and mortality in western societies, start early in life. However, it is not known what determinants are related to the vascular system in the young. In this thesis we studied the relation of specific determinants, including smoking during pregnancy, overweight, breast feeding and genes with cardiovascular risk factors and vascular characteristics in individuals aged 4 weeks, 5 years, and young adult age. Early life determinants We showed that smoke exposure during pregnancy was associated with thicker carotid intima media thickness (CIMT) in the young adult offspring. This association was independent of active smoking of the offspring. In an additional study we showed that smoking during pregnancy was related to both arterial wall stiffness and thickness in 5 year old offspring. This finding was independent of confounders. We concluded that smoking during pregnancy has a direct influence on the offspring’s vasculature in early childhood, which is still visible in young adulthood. Moreover, it was shown that healthy infants from mothers who smoked during pregnancy had 5.4 mmHg higher systolic blood pressure than infants not exposed to smoke during pregnancy. This observation was seen after adjusting for confounders. We concluded that the relation between smoking during pregnancy and offspring blood pressure is set in utero. Furthermore we showed that children at the age of 5 years, who had been exclusively breastfed in infancy for 3 to 6 months had an increased CIMT compared to those exclusively formula fed. Children exclusively breastfed for either less than 3 months or for more than 6 months showed no difference in CIMT compared to formula fed children. Additionally, no significant differences in carotid stiffness were observed. In conclusion, the duration of exclusive breastfeeding in infancy is related to CIMT at the age of 5 years in children exclusively breastfed for 3 to 6 months. Classical risk factors Overweight, a known CVD risk factor in adults, is an increasing public health threat in adults and particularly in children. It is unknown at what age overweight starts to takes its toll on the vasculature. We showed that increased body weight was related to thicker carotid arterial wall and increased stiffness. Specifically, increased measures of intra-abdominal fat were related to thicker arterial walls and increased stiffness, independent of BMI. These results demonstrate that increased general body mass, and particularly body fat distribution, are related to thicker and stiffer arteries already early in life. Genes Recently, twelve loci were identified in a genome wide association study as related to blood pressure independent of body mass index. This association could be confirmed in eight of these loci. We found that two SNPs that were not confirmed for an association with blood pressure, did show a relation with body size, a strong determinant of blood pressure, in young adults. No relations with waist-to-hip ratio were found with the blood pressure associated SNPs. Overall, these findings indicate that both genetic and environmental factors influence the cardiovascular system already from early life onwards