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

Abstract

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.

Lower HDL-C and apolipoprotein A-I are related to higher glomerular filtration rate in subjects without kidney disease

“…The inverse relationships of HDL-C and apoA-I with kidney function agree with some reported data obtained in the whole PREVEND cohort ( 24 ). Apparently opposite fi ndings were found when stratifying subjects without renal insuffi ciency according to plasma cystatin-C levels ( 25 ), although in adolescent American Aboriginals ( 40 ), in subjects with essential hypertension ( 41 ), or in type 2 diabetic individuals ( 42 ) no signifi cant associations of HDL-C with cystatin-C levels could be demonstrated. It was long believed that cystatin C concentration is a good marker of kidney function, being independent of demographic variables such as muscle mass, weight, or disease states.…”

Comparison of creatinine and cystatin C based eGFR in the estimation of glomerular filtration rate in Indigenous Australians: The eGFR Study

“…Our findings of cystatin C based equations being influenced by obesity are supported by other studies [28] including Asian and Indigenous populations [29][30][31]. One observational study of immigrant South Asians was also able to demonstrate that the relationship between increasing adiposity and eGFRcysC was largely explained by factors related with chronic inflammation, including c-reactive protein [30].…”

“…One observational study of immigrant South Asians was also able to demonstrate that the relationship between increasing adiposity and eGFRcysC was largely explained by factors related with chronic inflammation, including c-reactive protein [30]. In another study of Indigenous youth, cystatin C was strongly associated with the metabolic syndrome [31]. In contrast to our findings, however, other studies of Asian populations have reported that the combined eGFRcysC+cr equation was superior to eGFRcr [11,32,33].…”

Relationship Between Cystatin C and Coronary Artery Atherosclerosis Progression Differs by Type 1 Diabetes

“…42 In persons without DM cystatin C, as a marker of early renal dysfunction, could be on the causal pathway between increased BMI and CAD. 43 In T1D persons higher BMI has been associated with CAC, but its relationship with CAC severity was inverse or nonexistent. 44 In T1D patients, the relationship of glycemia to BMI (and other CVD risk factors) may not be as strong as the association of glycemia to CAD.…”