Elevated Serum Uric Acid Concentrations Independently Predict Cardiovascular Mortality in Type 2 Diabetic Patients

Abstract

OBJECTIVEThere is limited information on whether increased serum uric acid levels are independently associated with cardiovascular mortality in type 2 diabetes. We assessed the predictive role of serum uric acid levels on all-cause and cardiovascular mortality in a large cohort of type 2 diabetic individuals.RESEARCH DESIGN AND METHODSThe cohort included 2,726 type 2 diabetic outpatients, who were followed for a mean period of 4.7 years. The independent association of serum uric acid levels with all-cause and cardiovascular mortality was assessed by Cox proportional hazards models and adjusted for conventional risk factors and several potential confounders.RESULTSDuring follow-up, 329 (12.1%) patients died, 44.1% (n = 145) of whom from cardiovascular causes. In univariate analysis, higher serum uric acid levels were significantly associated with increased risk of all-cause (hazard ratio 19 [95% CI 1.12–1.27], P < 0.001) and cardiovascular (1.25 [1.16–1.34], P < 0.001) mortality. After adjustment for age, sex, BMI, smoking, hypertension, dyslipidemia, diabetes duration, A1C, medication use (allopurinol or hypoglycemic, antihypertensive, lipid-lowering, and antiplatelet drugs), estimated glomerular filtration rate, and albuminuria, the association of serum uric acid with cardiovascular mortality remained statistically significant (1.27 [1.01–1.61], P = 0.046), whereas the association of serum uric acid with all-cause mortality did not.CONCLUSIONSHigher serum uric acid levels are associated with increased risk of cardiovascular mortality in type 2 diabetic patients, independent of several potential confounders, including renal function measures.

Serum uric acid does not predict cardiovascular or all-cause mortality in type 2 diabetes: the Fremantle Diabetes Study

“…Since non-diuretic therapies for CVD such as statins and ACE inhibitors can raise or lower serum uric acid concentrations [18], we included the main CVD treatments in our analyses but they did not alter the non-significant relationship between serum uric acid and CVD death. As in the Verona Diabetes Study [2], we did not find that use of xanthine oxidase inhibitors was associated with CVD death. This suggests that lowering serum uric acid concentrations in this way does not have beneficial CVD effects.…”

“…In the present study, retinopathy, neuropathy, coronary disease and PAD were independent determinants of CVD death and/or all-cause mortality, while we also had near-complete baseline and outcome data for our patients. Since the 28% increased risk of CVD death per 0.1 mmol/l rise in serum uric acid in our univariate analyses declined to a non-significant 11% excess in the fully adjusted model (with the upper 95% CI equivalent to the Verona Study 27% point estimate [2]), it is likely that the difference in the range of data available for analyses helps explain the discrepant findings in the two studies. In addition, the Verona Diabetes Study patients were older and had been diabetic for a longer duration than those in the FDS despite exclusion of those with prior CVD, and may have been less representative of type 2 diabetes in the community as a result.…”

“…This situation pertained regardless of whether serum uric acid was included in Cox proportional hazard models as a continuous variable or as quartiles. Because of previous reports that uricaemia is of prognostic significance in older patients [4] and in an Italian population-based sample [2], we performed separate analyses in the patients in our cohort who were >65 years and from a southern European background. In neither case was serum uric acid an independent determinant of outcome.…”

“…Our data suggest that serum uric acid concentrations have a limited influence on CVD complicating type 2 diabetes. In the Verona Diabetes Study [2] which involved 2,726 type 2 patients followed for a mean of 4.7 years, each SD increment in serum uric acid (0.095 mmol/l) was associated with an independent 27% increase in the risk of CVD death in a fully adjusted Cox model. However, these authors excluded patients with a prior history of CVD, and nonrenal microvascular complications of diabetes were not included in any of the analyses.…”

“…In the case of type 2 diabetes, a recent Italian cohort study found that serum uric acid was independently associated with CVD mortality [2], but those with a prior history of CVD, malignancy, severe chronic airway disease and/or end-stage renal disease were excluded, and there was no significant relationship with allcause death. In two smaller studies in diabetic patients, serum uric acid was independently associated with all-cause mortality in a sample at relatively high CVD risk [3] and with CVD mortality in the elderly in a 'J-shaped' relationship [4].…”