The influence of selected biological, lifestyle risk factors and fitness on plasma Hcy and ADMA concentrations and vascular function : the AGAHL–study

Abstract

The prevalence of cardiovascular disease (CVD) increases with age. It is thus important to study the relationship that might exist between various cardiovascular risk factors within longitudinal studies. Homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) are two of these newly identified risk factors for CVD. They need to be studied in order to understand the underlying mechanisms involved in endothelial function, inflammation and arterial properties. The objective of this study was to investigate the relationship between (changes in) concentrations of homocysteine (Hcy), asymmetric dimethylarginine (ADMA), fitness, fatness, markers of endothelial function and inflammation, and arterial properties of healthy adults from the Amsterdam Growth and Health Longitudinal Study (AGAHLS). The AGAHLS is a suitable study to investigate the interactions between cardiovascular risk factors such as Hcy, ADMA, fitness, fatness, markers of endothelial function and inflammation, and arterial properties. The AGAHLS started in 1977 with a group of 13-year-old subjects. They were measured repeatedly over time, of which only the last two measurements (2000 at the age 36 and 2006 at the age of 42) were used in this study. The following variables were measured: - Fitness [direct and indirect VO2max, physical activity (kMETS.min/wk)]; - fatness (trunk fat mass, peripheral fat mass, peripheral lean mass); - markers of endothelial function [intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), endothelial selectine (E-selectine), plasma selectine (P-selectine), thrombomoduline, Von Willebrand factor (vWf)]; - inflammation markers [C-reactive protein (CRP), serum amyloid A (SAA), tumor necrosis factor α (TNF- α), interleukin-6 (IL-6) and interleukin-8 (IL-8)]; and - arterial properties [carotid artery intima-media thickness (IMT), carotid artery compliance coefficient (CA CC), carotid artery distensibility coefficient (CA DC), femoral artery compliance coefficient (FA CC), femoral artery distensibility coefficient (FA DC) and Young's elastic modulus (YEM)]. The relationships between the variables, namely the concentrations of Hcy, ADMA, fitness, fatness, markers of endothelial function and inflammation, and arterial properties were performed with generalized estimating equations (GEE) analyses. Linear regression analyses were applied to analyse the relationships between changes in concentrations of Hcy and ADMA, and changes in fitness, fatness, markers of endothelial function and inflammation, and arterial properties. Results of the GEE analyses indicated that 1 ml/min/kg higher VO2max fitness was significantly related to a -0.81 nmol/L lower plasma Hcy concentration (95% confidence interval [-1.53 - -0.09] p=0.03). However, this relationship was attenuated after adjustment for smoking behaviour. Significant relationships were found between plasma ADMA concentrations and endothelial markers ICAM (B=71.67 [5.01 - 138.33] p=0.04) and thrombomoduline (B=0.89 [0.09 - 1.68] p=0.029). A significant inverse relationship was seen between changes in plasma ADMA concentrations and changes in vWf (B= -42.39 [-82.81 - -1.98] p=0.04). In conclusion, this study has demonstrated that a significant longitudinal relationship exists between plasma ADMA concentrations and endothelial markers (i.e. ICAM, thrombomoduline). Furthermore, an inverse significant relationship has been found between changes in ADMA concentrations and changes in the vWf. It is recommended that future investigations include an older population and diverse ethnic groups.