Increased Serum Uric Acid: Consequence or Cause of Increased Cardiovascular Risk

Background/Purpose: Reports on cardiovascular (CV) disease in hyperuricemia and gout show conflicting results. Some studies show hyperuricemia to be an independent risk factor for CV events and death, others find no such associations or only with gouty arthritis. Gout and hyperuricemia have also been associated with individual CV risk factors such as increasing age, male sex, overweight, hypertension, dyslipidemia, diabetes and inflammation. Studies evaluating the complex associations between serum uric acid, inflammation, gouty arthritis and CV risk are lacking. This study was done to investigate the associations between serum uric acid and cardiometabolic risk factors and estimated CV risk in patients with gouty arthritis, non-gouty arthritis, and degenerative joint disease. To explore the effect of uric acid lowering therapy (ULT) on CV risk.

Methods: Analysis of the relation between serum uric acid and estimated 10-year risk of CV death (SCORE risk calculation, low risk version corrected for diabetes by increasing age with 15 years) and individual CV risk factors, i.e. systolic blood pressure (SBP), TC/HDL ratio (TC/HDL), diabetes and smoking in patients with osteoarthritis (OA, n197), rheumatoid arthritis (RA, n675) and gouty arthritis (GA, n201) in a cohort of consecutive patients attending the Arthritis Center Twente in 2009. Subanalysis of the effect of uric acid lowering therapy (ULT; allopurinol or benzbromarone, target serum uric acid 0.36 mmol/L) on estimated 10-year CV risk in GA patients. Differences between groups and associations between CV risk variables and tertiles of serum uric acid were tested with ANOVA (for continuous cardiovascular risk factors) or Chi squared statistics (for nominal cardiovascular risk factors), adjusted for differences by age and sex.

Results: mean estimated 10-year CV risk was significantly higher in GA (GA 9.5% vs 5.7% in OA and RA, p0.05). In RA and OA mean estimated 10-year cardiovascular risk as well as individual cardiometabolic parameters (OA: mean SBP, mean TC/HDL; RA: mean SBP, mean TC/HDL, prevalence diabetes. p0.05) correlated with serum uric acid values. None of these correlations were present in GA. In GA plasma uric acid was lower in patients on ULT (0.32 mmol/l ULT vs 0.47 mmol/l non-ULT, p0.05), age and frequency of CV events did not differ from non-ULT users. ULT did not affect mean estimated 10-year CV risk (9.7% ULT vs 8.9% non-ULT, p0.05).

Conclusion: Gouty arthritis is a red flag for increased CV risk, as shown by higher prevalence of previous CV events and increased metabolic parameters of CV risk. Serum uric acid is associated with metabolic parameters of CV risk and 10-year risk of CV death. Effective ULT does not affect 10-year CV risk. Increased serum uric acid is therefore probably secondary to a high cardiometabolic risk profile.