Elsevier

Annals of Epidemiology

Volume 10, Issue 3, April 2000, Pages 136-143
Annals of Epidemiology

Original reports
Serum Uric Acid and Risk of Coronary Heart Disease: Atherosclerosis Risk in Communities (ARIC) Study

https://doi.org/10.1016/S1047-2797(99)00037-XGet rights and content

Abstract

PURPOSE: Approximately half of previous studies on serum uric acid have reported it to be an independent risk factor for coronary heart disease (CHD). We tested this hypothesis in the Atherosclerosis Risk in Communities (ARIC) Study.

METHODS: A total of 13,504 healthy middle-aged men and women were followed prospectively for up to eight years. We identified 128 fatal and nonfatal CHD events in women and 264 in men.

RESULTS: The age-, race-, and ARIC field center-adjusted relative risk of CHD for sex-specific quartiles of serum uric acid were 1.0, 1.39, 1.08, and 2.35 in women (p for trend = 0.009) and 1.0, 1.03, 0.89, and 1.21 in men (p for trend = 0.44), respectively. However, serum uric acid was correlated positively with many risk factors, and after multivariable adjustment, there was little evidence of an association of uric acid with CHD in either sex.

CONCLUSIONS: Our results are not consistent with serum uric acid being an independent risk factor for CHD.

Introduction

Uric acid is the final breakdown product of purine degradation in humans. Although elevated serum uric acid is most intimately associated with gout, Gertler and coworkers observed, nearly fifty years ago, an association between elevated serum uric acid and coronary heart disease (CHD) (1). Subsequent studies investigating the complex association of elevated serum uric acid and CHD have yielded inconsistent results. While some studies have found hyperuricemia to be an independent risk factor for CHD 1, 2, 3, 4, 5, 6, 7, 8, 9, others have concluded that the association was confounded by the relationship of uric acid with established risk factors for CHD such as hypertension, obesity, hyperlipidemia, or diabetes mellitus 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. There have been at least eleven prospective studies 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16, 17, 18, 19 of which five showed an independent association 3, 4, 5, 6, 7, 8, 9 between uric acid and CHD. Noting a tendency for the above risk factors to occur together, some researchers have postulated that elevated serum uric acid is a physiological marker of obesity and insulin resistance rather than a direct cause of atherosclerotic disease 10, 21.

The goals of this study were, first, to investigate the association of hyperuricemia with known risk factors for CHD in a middle-aged population of men and women and, second, to assess whether there was an independent association of uric acid with CHD incidence when adjusting for known risk factors for CHD and variables associated with elevated uric acid.

Section snippets

Study Design and Subjects

The Atherosclerosis Risk in Communities (ARIC) Study is a multi-center prospective cohort study investigating the natural history of atherosclerotic disease in four US communities: Forsyth County, North Carolina; Jackson, Mississippi; Washington County, Maryland; and the northwest suburbs of Minneapolis, Minnesota (22). The cohort comprised 15,792 men and women aged 45 to 64 years who were selected by probability list or area sampling. Only Blacks were recruited in the Jackson study center.

From

Results

This analysis included 7600 women and 5904 men aged 45–64 years and free of CHD and cancer at baseline. Serum uric acid levels ranged from 0.2 to 15.9 mg/dL with a (mean [SD]) of (5.99 [1.54] mg/dL) and appeared to be normally distributed upon visual inspection. Women who developed incident CHD (n = 128) had higher (p < 0.001) age-, race- and field center-adjusted mean baseline serum uric acid levels than did women who remained free of CHD (Table 1). However, the serum uric acid levels of men

Discussion

In this cohort of middle-aged men and women, serum uric acid levels were directly associated with most CHD risk factors including hypertension, systolic blood pressure, LDL cholesterol, triglycerides, low HDL cholesterol, BMI, waist/hip ratio, smoking, and alcohol intake. In a model adjusting for age, race, and ARIC field center, serum uric acid was directly and moderately associated with CHD incidence in women only. The relative risk in women was elevated only for the highest quartile,

Acknowledgements

This research was supported by contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 from the U.S. National Heart, Lung, and Blood Institute. The authors thank Lori Boland for programming assistance, and the following staff of the ARIC Study: Phyllis Johnson, Marilyn Knowles, and Catherine Paton from the University of North Carolina, Chapel Hill, NC; Shirley Cothern, Amy Haire, Kim Jones, and Delilah Posey from the University of North

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