Introduction The pathological changes of early atherosclerosis (fatty streaks and fibrous plaques) may be observed in the young and can be reflected
in vivo
by the carotid intima-media thickness (CIMT), measured by ultrasound. CIMT is a reliable marker of subclincal atherosclerosis in adults and traditional cardiovascular risk factors present in childhood predict CIMT in adulthood. However, the determinants of CIMT in childhood are largely unknown. We assessed the influence of traditional cardiovascular risk factors and also asymmetric dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthesis) on CIMT, in healthy 8-year old children.
Methods 406 community-based children (age 8.0±0.1, 49% girls) had anthropometry, systolic and diastolic blood pressure (SBP, DBP) and mean left and right CIMT measured. A non-fasting blood sample was collected for HDL, non-HDL cholesterol, apolipoprotein B (apo B), high sensitivity CRP (hs-CRP) and ADMA (measured by ELISA). Correlates of CIMT were evaluated.
Results Mean (± sd) values were CIMT 0.59±0.06 mm, HDL 1.46±0.37 mmol/L, non-HDL cholesterol 2.96±0.70 mmol/L, apo B 0.64±0.15 mmol/L, and ADMA 0.91±0.22 μmol/L; median hs-CRP was 0.3 mg/L (interquartile range 0.21 to 1.09 mg/L). On univariate analysis, CIMT was associated significantly with SBP (r=0.164, p<0.001), DBP (r=0.105, p<0.017), HDL (r= −0.142, p<0.006) and ADMA (r=0.182, p<0.001). Measures of body size, apo B and hs-CRP were not significantly related to CIMT. On multivariable analysis, HDL (β coefficient = −0.118, p<0.035) and ADMA (β coefficient = 0.175, p<0.002) were significant independent determinants of CIMT in a model adjusted for all measured risk factors and sex.
Conclusions Lower HDL-cholesterol and higher levels of ADMA, an endogenous inhibitor of nitric oxide synthesis, are significantly associated with CIMT in childhood. These data may permit earlier cardiovascular risk stratification and suggest novel mechanisms whereby HDL and ADMA might be modulating atherogenesis at an earlier stage than previously envisaged.
Regulation of Cytokine-Induced Nitric Oxide Synthesis by Asymmetric Dimethylarginine
