Biomarkers of vascular function and structure in young
healthy adults
av
Paul Pettersson-Pablo
Akademisk avhandling
Avhandling för medicine doktorsexamen i medicin, som kommer att försvaras offentligt fredag den 29 januari 2021 kl. 09.00, Hörsal C1, Campus USÖ, Örebro universitet
Opponent: Professor Anders Larsson Institutionen för medicinska vetenskaper,
Klinisk kemi, Uppsala universitet Uppsala
Örebro universitet Institutionen för medicin
Abstract
Paul Pettersson-Pablo (2021): Biomarkers of vascular function and struc-ture in young healthy adults. Örebro Studies in Medicine 226
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 child-hood but typically not manifesting as symptomatic disease until late adulthood (after 60 years of age). The identification of younger individ-uals with a high risk for early intervention has a higher potential of pre-venting morbidity and mortality.
In this thesis, part of the Lifestyle, Biomarkers and Atherosclerosis study (LBA), the earliest stages of vascular dysfunction have been exam-ined in a population of young, healthy, non-smoking subjects. Vascular function and structure measurements predict a future risk of cardiovas-cular 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 inflam-matory 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 con-centration 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 cated in CVD. In multivariable linear regression models, proteins impli-cated in hemostasis, inflammatory signaling and chemoattraction corre-lated with different vascular function and structure measurements. In Paper 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 concentra-tions of serum biomarkers can be detected in subjects with increased body fat and unfavorable vascular function and structure.
Ke ywords: atherosclerosis, vascular function, vascular structure, body composition, age, inflammation, clinical chemistry, biomarker
Paul Pettersson-Pablo, School of Medical Sciences, Örebro University, SE-701 82 Örebro, Sweden, paul.pettersson-pablo@regionorebrolan.se