Is serum urate causally associated with incident cardiovascular disease?

With studies reporting both positive and negative associations, the influence of serum urate on incident cardiovascular disease (CVD) is uncertain. We sought to determine whether serum urate is causally associated with incident CVD.

Participants were aged 30-80 years and were screened for CVD risk in primary care between 2006 and 2009. Participants had blood pressure, lipids, age and ethnic group recorded at assessment, with record linkage providing drug dispensing, hospital diagnoses and laboratory test results. Outcomes were derived from hospital diagnoses and mortality records until December 2009. Cox models were used to assess the influence of exposures on outcomes.

A total of 78 707 people, free of CVD, were enrolled, and 1328 CVD events occurred during follow-up. Serum urate was recorded before baseline assessment in 43% (34 008/78 707) of participants. After adjustment for confounding factors, a 2 s.d. difference in serum urate (0.45 vs 0.27 mmol/l) was associated with a hazard ratio (HR) of 1.56 (95% CI 1.32, 1.84). This was more than double that of the equivalent distributional change in high-density lipoprotein cholesterol (adjusted HR 1.22) and one-third greater than that for HbA1c (adjusted HR 1.41).

Serum urate is likely to be causally associated with CVD. This supports public health action to reduce urate levels in populations with significant burdens of the disease.