Cystatin C is associated with cardiovascular risk factors and metabolic syndrome in Aboriginal youth

Serum concentration of cystatin C, a marker of glomerular filtration, has been associated with incident cardiovascular disease (CVD), although the pathophysiology underlying this association remains unclear. As North American Aboriginal populations are experiencing high prevalence rates of CVD in early adulthood, evaluation of cardiovascular (CV) risk factors in Aboriginal children may provide insight into the early pathophysiology of vascular disease. In this context, we sought to determine whether cystatin C is associated with CV risk factors in Aboriginal youth. Serum concentrations of cystatin C were assessed in a population-based study of a Canadian Aboriginal community, involving 230 children aged 10-19 years. Cystatin C was higher in the 41 children with pediatric metabolic syndrome (MetS) (defined using an age- and gender-specific version of Adult Treatment Panel III criteria) than in the 189 children free of MetS (0.87 vs 0.81 mg/l, p = 0.0026). After adjustment for age, gender, and glomerular filtration rate (estimated using the Schwartz formula), cystatin C was (1) positively correlated with waist circumference, body mass index, systolic blood pressure, triglycerides, fasting insulin, and leptin (all r >/= 0.18, p < 0.05), and (2) inversely related to high-density lipoprotein (HDL) cholesterol (r = -0.21, p = 0.0023). These associations, however, were attenuated with further adjustment for insulin resistance, as measured by the homeostasis model assessment (HOMA-IR). On multivariate analysis, waist circumference emerged as a positive independent determinant of cystatin C, whereas female gender and age were negative correlates. Cystatin C levels progressively increased in association with the number of metabolic syndrome component disorders coexistent within an individual (trend p = 0.0072). In summary, increased cystatin C is associated with an enhanced CV risk factor profile in Aboriginal youth and may be an early event in the natural history of vascular disease.