To Örebro University

Atherosclerosis is a disease affecting the blood vessels in the body. Its pathophysiologic mechanisms involve infiltration of the vessel walls by fatty matter and immune cells. This process is slow, starting in childhood but typically not manifesting as symptomatic disease until late adulthood (after 60 years of age). The identification of younger individuals with a high risk for early intervention has a higher potential of preventing morbidity and mortality.

In this thesis, part of the Lifestyle, Biomarkers and Atherosclerosis study (LBA), the earliest stages of vascular dysfunction have been examined in a population of young, healthy, non-smoking subjects. Vascularfunction and structure measurements predict a future risk of cardiovascular disease (CVD). The measurements were analyzed in relation to clinical chemistry analyses of various biomarkers in serum and plasma that have been associated with inflammation or cardiovascular risk. A secondary aim was to examine estrogen containing contraceptive use and its relation to the CVD biomarkers.

In Paper I and Paper II of the thesis, the association between inflammatory biomarkers, body fat percentage and vascular function and structure measurements was examined in multivariable linear regression models. A higher body fat percentage predicted an increased serum concentration of C-reactive protein (CRP) and orosomucoid. In Paper II, a higher body fat percentage and a higher CRP were associated with a more unfavorable vascular function and structure.

In Paper III and Paper IV, we employed two multiplex proteomics panels to analyze inflammatory proteins and proteins previously implicated in CVD. In multivariable linear regression models, proteins implicated in hemostasis, inflammatory signaling and chemoattraction correlated with different vascular function and structure measurements. InPaper IV, insulin-like growth factor-binding protein 1 (IGFBP1) and IGFBP2 were independently predictive of an increased vascular stiffness.

In conclusion, even in young, healthy individuals, altered concentrations of serum biomarkers can be detected in subjects with increased body fat and unfavorable vascular function and structure.