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A Prospective Cohort Study

Leo K. Niskanen, MD, PhD; David E. Laaksonen, MD, PhD, MPH; Kristiina Nyyssönen, PhD; Georg Alfthan, PhD; Hanna-Maaria Lakka, MD, PhD; Timo A. Lakka, MD, PhD; Jukka T. Salonen, MD, PhD

Arch Intern Med. 2004;164:1546-1551.

Background  Despite abundant epidemiologic evidence, the role of elevated serum uric acid level as a cardiovascular risk factor is controversial. We assessed the predictive value of serum uric acid levels for cardiovascular and overall mortality.

Methods  A population-based prospective cohort study was performed of 1423 middle-aged Finnish men initially without cardiovascular disease, cancer, or diabetes. The main outcome measure was death from cardiovascular disease and any cause.

Results  The mean follow-up was 11.9 years. There were 157 deaths during follow-up, of which 55 were cardiovascular. In age-adjusted analyses, serum uric acid levels in the upper third were associated with a greater than 2.5-fold higher risk of death from cardiovascular disease than levels in the lower third. Taking into account cardiovascular risk factors and variables commonly associated with gout increased the relative risk to 3.73. Further adjustment for factors related to the metabolic syndrome strengthened the risk to 4.77. Excluding the 53 men using diuretics did not alter the results. In age-adjusted analyses, men with serum uric acid levels in the upper third were 1.7-fold more likely to die of any cause than men with levels in the lower third. Adjustment for further risk factors strengthened the association somewhat.

Conclusions  Serum uric acid levels are a strong predictor of cardiovascular disease mortality in healthy middle-aged men, independent of variables commonly associated with gout or the metabolic syndrome. Serum uric acid measurement is an easily available and inexpensive risk marker, but whether its relationship to cardiovascular events is circumstantial or causal remains to be answered.

From the Department of Medicine, Kuopio University Hospital, Kuopio, Finland (Drs Niskanen and Laaksonen); Research Institute of Public Health, Kuopio (Drs Nyyssönen and Salonen); Biomarker Laboratory, Department of Health and Functional Capacity, National Public Health Institute, Helsinki, Finland (Dr Alfthan); Pennington Biomedical Research Center, Louisiana State University, Baton Rouge (Drs H.-M. Lakka and T. A. Lakka); Department of Public Health and General Practice, University of Kuopio (Drs H.-M. Lakka and Salonen); and Inner Savo Health Center, Suonenjoki, Finland (Dr Salonen). The authors have no relevant financial interest in this article.

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