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Serum Uric Acid and Cardiovascular Disease Risk
- Bruce F. Culleton, MD;
- Martin G. Larson, ScD; and
- Daniel Levy, MD
- University of Calgary; Calgary, Alberta, Canada T2N 2T9 (Culleton) National Heart, Lung, and Blood Institute; Framingham Heart Study; Framingham, MA 01702 (Larson) National Heart, Lung, and Blood Institute; Framingham Heart Study; Framingham, MA 01702 (Levy)
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IN RESPONSE:
First, we thank Drs. Vaccarino and Krumholz for their flattering editorial about our article, particularly their praise of the contributions of the Framingham Heart Study to cardiovascular disease risk assessment (1). We are also pleased to respond to Dr. Alderman's comments.
We believe that critical differences in the designs of the studies may explain their disparate results. First, our report used data collected from a community-based sample. In contrast, Alderman and colleagues' study (2) was clinic-based and included only hypertensive patients. Second, residual confounding may also account for some of the differences. The NHANES I epidemiologic follow-up study (3) seems to have accounted for diabetes by excluding diabetic patients from the longitudinal analyses, but diabetes was identified solely by self-report. This may be important because up to 50% of persons with type 2 diabetes are unaware of their disease. In addition to inadequate adjustment for diabetes, the Chicago Heart Association study also failed to account for diuretic use (4).
We believe that the concept of causality also deserves attention. If a factor is believed to be a cause of a disease, exposure to the factor must precede the development of the disease. We excluded persons with clinically apparent cardiovascular disease (CVD) at baseline to determine whether a temporal relation between serum uric acid levels and CVD existed. In contrast, 17% of Alderman and colleagues' patients had known CVD at baseline (3). Furthermore, serum uric acid level was no longer predictive of incident CVD in persons without CVD at baseline. Similarly, the Chicago Heart Association and the Systolic Hypertension in the Elderly Program studies also included persons with prevalent CVD. The serum uric acid-CVD relation also lacks other evidence necessary to determine causality, including biological plausibility and consistency from study to study.
In summary, on the basis of available evidence, we believe that serum uric acid may be a marker for poor prognosis in high-risk populations, such as persons with congestive heart failure, other overt CVD, and possibly hypertension. The association of serum uric acid with CVD risk in some observational studies is probably the result of residual confounding (especially by diuretic use); in persons without CVD, serum uric acid has no predictive value beyond that of established cardiovascular risk factors. On the basis of published observational studies to date, we conclude that there is insufficient evidence to support a causal role for serum uric acid in promotion of CVD. Our study provides additional evidence against a causal relation.
Bruce F. Culleton, MD
University of Calgary; Calgary, Alberta, Canada T2N 2T9
Martin G. Larson, ScD
National Heart, Lung, and Blood Institute; Framingham Heart Study; Framingham, MA 01702
Daniel Levy, MD
National Heart, Lung, and Blood Institute; Framingham Heart Study; Framingham, MA 01702
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
