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Relations of Hyperuricemia with the Various Components of the Insulin Resistance Syndrome in Young Black and White Adults: The CARDIA Study

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Abstract

PURPOSE: To assess the association of hyperuricemia with the various components of the Insulin Resistance Syndrome (IRS) in a biracial cohort of young adults.

METHODS: Cross-sectional study in 4053 young black and white adults aged 18–30 years from the Coronary Artery Risk Development in Young Adults (CARDIA) study.

RESULTS: Body mass index (BMI), fasting insulin, and triglycerides were significantly higher, and high density lipoprotein (HDL)-cholesterol lower in subjects with hyperuricemia (uric acid ⩾ 7.0 mg/dl in males; ⩾ 6.0 mg/dl in females) (all p < 0.001). BMI showed the strongest positive correlation with uric acid among the IRS components. Significant associations of hyperuricemia with these risk factors were observed in all sex-race groups, which persisted after controlling for possible confounders including age, education, physical activity, smoking, alcohol intake, oral contraceptive use, and creatinine. Further adjustment for BMI and/or waist-to-hip ratio caused a large decrease in the strength of the associations. Adjustment for insulin also lead to decreases; however, the influence of fasting insulin appeared weaker than obesity. Even after controlling for obesity, insulin, and the other components of the IRS, male subjects in both races in the upper tertile of triglycerides were still more likely to have hyperuricemia.

CONCLUSIONS: The association of hyperuricemia with most aspects of the IRS may result predominantly from their covariation with adiposity and secondarily with insulin level. Elevated triglyceride level seems to have an independent relationship with hyperuricemia in males. The relationship between hyperuricemia and cardiovascular disease observed in previous studies may be secondary to its association with the IRS.

Introduction

Hyperuricemia appeared to be an independent risk factor for coronary artery disease in several studies 1, 2, 3. There has been no well-established etiologic explanation for this association. The Insulin Resistance Syndrome (IRS), a cluster of metabolic abnormalities related to insulin resistance 4, 5, 6, also appears to be a strong risk factor for cardiovascular disease [7]. There is evidence that hyperuricemia is part of the IRS. High uric acid concentrations have been reported to be closely associated with parts of the IRS including hyperinsulinemia, impaired glucose tolerance [8], hypertension [9], dyslipidemia, specifically high triglyceride levels and low high density lipoprotein (HDL)-cholesterol concentrations [10], and obesity [11], in particular abdominal adiposity [12]. Uric acid by itself may not be an independent risk factor for arteriosclerosis but is secondarily associated with a variety of established etiologic factors for cardiovascular disease [13]. There have been few reports that evaluated with which of the components of the IRS hyperuricemia is associated and those which have, have provided conflicting results as to whether the predominant association is with hyperinsulinemia or obesity 12, 14. There is one report indi- cating that the association of hyperuricemia with hypertriglyceridemia may be independent of obesity and insulin [15].

Most of these previous studies have been done in Caucasian populations and ethnic differences in the association of uric acid with other components of the IRS have not been studied extensively. Studies on serum uric acid and the IRS in African-American populations are sparse 12, 16, 17. Only a few studies have been done in normal young adults. Such studies could lead to a better understanding of the early evolution of these associations 12, 16. The Coronary Artery Risk Development in Young Adults (CARDIA) study provides the opportunity to evaluate the association between hyperuricemia and the IRS and its components in a large biracial population of male and female young adults with a low prevalence of potential confounding factors including use of diuretics or other antihypertensive drugs [18], or clinically manifested diseases including hypertension, diabetes mellitus, lipid disorders, or gout. Therefore, the aim of this study was to examine the associations of hyperuricemia with the various components of the IRS in the CARDIA cohort. In addition, we also evaluated whether the associations of hyperuricemia with glucose, triglycerides, HDL-cholesterol, and blood pressure could be explained by obesity, insulin resistance, or other characteristics, including creatinine and alcohol consumption.

Section snippets

Study Subjects

The CARDIA study is a prospective follow-up study to investigate the impact of lifestyle and other factors on the evolution of cardiovascular risk factors in a biracial cohort of young adults aged 18–30 years at baseline. The study design, recruitment of participants, and methods have been described elsewhere [19]. The original sample comprised 5115 subjects with approximately equal numbers of blacks and whites for both sexes. The present study is a cross-sectional analysis of the baseline data

Descriptive Statistics

Race- and sex-specific physiologic and laboratory measurements are given in Table 1. In the General Linear Model, all of the variables showed significant differences by race and gender (p < 0.001), except BMI and age (no sex difference) and waist-to-hip ratio, diastolic blood pressure, and alcohol (no race differences). Significant race-sex interactions were also observed for all variables except glucose, age, uric acid, diastolic blood pressure, and alcohol. Serum uric acid was significantly

Discussion

The results of this study suggest that hyperuricemia is related to various components of the IRS, including higher BMI, waist-to-hip ratio, blood pressure, triglycerides, fasting insulin concentrations, and lower HDL-cholesterol in young adults of both races and sexes. A strong association was found with obesity (BMI), whereas the relation with central adiposity (high waist-to-hip ratio) was less pronounced. The mechanisms by which hyperuricemia is related to such a variety of risk factors are

Acknowledgements

This work was supported by a scholarship from the German Academic Exchange Service, Bonn, Germany. The authors are thankful to Dr. K. Liu and Dr. A. R. Folsom for their useful comments and to Miss P. M. Heim from the CARDIA Coordinating Center for her excellent technical assistance in reviewing the analyses.

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