Abstract
Background: Failure to diagnose preclinical cardiovascular disease in youth misses a major opportunity to prevent the long-term consequences of this disease. We have conducted a pilot study to evaluate surrogate vascular markers (SVMs) that are associated with early arterial injury including flow-mediated vasodilatation, carotid intima media thickness (IMT), arterial stiffness, and biomarkers including cell adhesion molecules (ICAM-1, VCAM-1), methylarginines (asymmetric dimethylarginine [ADMA], symmetric dimethylarginine [SDMA]), and C-reactive protein (C-RP). We hypothesized that one or more of these SVMs which are linked to early pathological vascular changes will identify high-risk youth with early vascular injury compared to a healthy group and that these markers will tend to normalize with risk factor reduction. We further hypothesized that one or more of the markers will correlate with the Pathological Determinants of Atherosclerosis in Youth (PDAY) risk score.
Methods: Ten subjects without any known risk factors and 22 hypercholesterolemic (HC) youth, aged 10–20 years were recruited from the pediatric clinic. The majority of the HC group was also obese. The HC group was randomized to diet + 20 mg of simvastatin vs. placebo for 24 weeks followed by a forced titration to 40 mg vs. placebo for 24 weeks ending with a final evaluation after a 12 week washout period of diet alone.
Results: The markers that best distinguished the HC from the control subjects were C-RP (P=0.03), VCAM-1 (P=0.05) and SDMA (P=0.04). With the exception of ICAM-1 and C-RP, the marker values improved in the treatment group more than the placebo group and the relative changes were the largest for the methylarginines, a marker closely tied to insulin resistance. The markers that demonstrated the highest correlation with the number of risk factors were VCAM-1 (r=0.45, P=0.055) and SDMA (r=0.48, P=0.04). PDAY risk scores were calculated for each subject and SDMA (r=0.50, P=0.03) and Arg/SDMA (r=−0.50, P=0.04) again emerged as the most highly correlated SVMs. Consistent with the relatively low PDAY risk scores and a minimally thickened IMT, the data suggest that the majority of subjects do not have advanced atherosclerotic changes. We conclude that SVMs are a useful index of vascular injury in high-risk youth.
- Received September 11, 2008.
