Novel cardiovascular risk factors in childhood

University dissertation from Department of Pediatrics, Lund University

Abstract: Individuals with type 1 diabetes (T1D) have a 2 to 3-fold increased risk for cardiovascular disease compared to non-diabetic subjects. Exposure to a broad panel of risk factors in childhood may cause vascular damage with potentially long-term consequences for cardiovascular morbidity. The aims of the studies were to investigate in young patients with T1D whether: frequency of acute infections correlates with atherogenic vascular changes (Study I); diabetes-predisposing genotype HLA-DQ 2/8 is associated with phenotypes of atherosclerosis and systemic microvascular dysfunction (Study II-III); exposure to environmental tobacco smoke (ETS) affects heart rate variability (HRV), and whether this association is influenced by diabetes-risk HLA (Study IV). The aim of study V was to investigate in an animal model susceptible to vascular disease whether repeated challenge with a respiratory pathogen poses cumulative adverse effects on microvascular function. Our findings suggest that in young patients with T1D: diabetes-risk genotype HLA DQ 2/8 is associated with functional disturbances in both large arteries and microcirculation, and with atherogenic lipid phenotype (studies II and III); frequent exposure to ETS is associated with disturbances in HRV, especially in those with diabetes-risk genotype HLA-DQ 2/8 (study IV); high frequency of RTI is associated with early signs of accelerated atherosclerosis in carotid artery, particularly in those regularly exposed to ETS (study I). At least in a hypercholesterolemic milieu, the risk of developing microvascular dysfunction seems to rise with increasing number of infectious episodes (study V). Further studies are needed to provide additional mechanistic insights into the putative gene-environment interactions on the cardiovascular system in young patients with T1D, and to investigate eventual relationship to cardiovascular complications later in life. Also, large-scale prospective studies on young populations presenting diabetes-risk (as well as other autoimmunity-risk) HLA are needed to elucidate whether these putative gene-environment influences on the cardiovascular system may be present already before the onset of the disease predisposed by these HLA.