Low sensitivity for the metabolic syndrome to detect uric acid elevations in females and non-Hispanic-black male adolescents: An analysis of NHANES 1999–2006
Introduction
Uric acid is a product of purine breakdown that is linked to oxidative stress [1] and has emerged in adults as an independent risk factor for future cardiovascular disease (CVD) [2], [3], type 2 diabetes mellitus (T2DM) [4], [5], hypertension [6] and renal failure [7]. Among adolescents, levels of uric acid are associated with an increase in carotid artery media thickness [8] and future hypertension [9]. These associations have raised the prospect of using uric acid as a marker of future disease risk [10].
Uric acid is also tightly linked to the metabolic syndrome (MetS) [11], [12], a cluster of cardiovascular risk factors including elevated waist circumference (WC), increased blood pressure (BP), high triglycerides, low HDL-cholesterol and fasting hyperglycemia. Currently utilized criteria for diagnosing MetS such as those from the Adult Treatment Panel III (ATP-III) are based on specific cut-off values for these individual components [13]. MetS is strongly associated with insulin resistance and is a predictor of future T2DM in adolescents [14] and of future cardiovascular disease in adults [15]. Indeed, some have advocated that a diagnosis of MetS be a trigger for increased intervention among obese adolescents [16], who are at increasing risk for future CVD [17].
However, MetS exhibits racial/ethnic discrepancies that may decrease its effectiveness in predicting long-term risk for disease among all ethnicities [18], [19], [20]. Non-Hispanic-black adolescents exhibit a lower prevalence of MetS despite having a higher degree of insulin resistance [21], [22] and higher rates of T2DM [23], [24] and death from CVD [25]. This suggests that among non-Hispanic-black adolescents MetS may be under-diagnosed [26]. Additionally, females have an overall lower prevalence of MetS than males [19] but appear to have a tighter link between high uric acid and CVD [12].
Given the long-term associations of elevated uric acid and future disease, the association of uric acid with MetS, and racial/ethnic and gender discrepancies in MetS, our goal was to evaluate the ability of a classification of MetS to identify individuals with elevated uric acid levels on a race/ethnicity- and gender-specific basis. We applied a commonly used set of pediatric MetS criteria (the ATP-III criteria adapted for use in adolescence [11], [22], [27]) to adolescent data from the National Health and Nutrition Examination Survey (NHANES), with the hypothesis that MetS would perform more poorly at detecting elevated uric acid levels among non-Hispanic black adolescents than among non-Hispanic whites and Hispanics. In such a way we aimed to further detail racial/ethnic differences in currently used MetS criteria in assessing long-term risk.
Section snippets
Methods
Data were obtained from NHANES (1999–2006), a complex, multistage probability sample of the US population. These annual cross-sectional surveys are conducted by the National Center for Health Statistics (NCHS) of the Centers for Disease Control (CDC), with randomly selected subjects undergoing anthropometric and blood pressure measurements, answering questionnaires and undergoing phlebotomy (http://www.cdc.gov/nchs/nhanes.htm). The NCHS ethics review board reviewed and approved the survey and
Sample characteristics
The sample consisted of 3296 non-Hispanic-white, non-Hispanic-black and Hispanic adolescents age 12–19 y.o. with data for all variables tested. Numbers of subjects with and without and values for individual MetS components by race/ethnicity are shown for male and female subjects in Table 1, Table 2, respectively. The numbers of subjects with MetS are the total number in the sample and have not been adjusted to reflect oversampling of minorities in NHANES. Regarding use of anti-hypertensive
Discussion
We found racial/ethnic and gender differences in the ability for a diagnosis of MetS to identify adolescents with elevated levels of uric acid. While on a population level MetS exhibits a reasonable sensitivity to identify elevations in uric acid [30], in an ethnicity-specific analysis MetS performed more poorly in the ability to do so among females compared to males and among non-Hispanic-black males compared to Hispanics and non-Hispanic whites. These data may have implications regarding the
Acknowledgement
This work was supported by NIH grants 5K08HD060739-03 (MDD) and 1R21DK085363 (MDD and MJG).
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