Association of serum uric acid with incident vascular calcification in patients with type 2 diabetes mellitus: a retrospective cohort study.

BACKGROUND

Vascular calcification (VC) is common among patients with type 2 diabetes mellitus (T2DM) and is associated with adverse cardiovascular outcomes. Although experimental evidence suggests that elevated serum uric acid (SUA) may promote VC, its clinical relevance in patients with T2DM remains unclear.

METHODS

We conducted a retrospective cohort study based on electronic medical records from the Central Hospital of Dalian University of Technology. The study included 665 hospitalized patients with T2DM who had no evidence of VC on baseline pulmonary computed tomography (CT) and underwent follow-up pulmonary CT. Incident VC was defined as newly detected, radiologically visible coronary artery calcification (CAC), aortic calcification, or both on mediastinal-window pulmonary CT. Associations between SUA and incident VC were assessed using Kaplan-Meier analysis, multivariable Cox regression, restricted cubic spline (RCS)analysis, subgroup analyses, and sensitivity analyses. Predictive performance was assessed using time-dependent receiver operating characteristic (ROC) analysis with inverse probability of censoring weighting (IPCW).

RESULTS

During a median follow-up of 2.25 years, incident VC developed in 315 patients. In the fully adjusted model, each 1-standard-deviation (SD) increase in SUA was associated with a higher risk of incident VC (HR, 1.271; 95% CI, 1.138-1.420; P < 0.001). Compared with the lowest SUA quartile, the third and fourth quartiles were associated with higher risks of incident VC (HR, 1.634; 95% CI, 1.125-2.375; P = 0.010; and HR, 2.075; 95% CI, 1.432-3.006; P < 0.001, respectively). RCS analysis showed an approximately linear association between SUA and incident VC. Time-dependent areas under the curve (AUCs) for SUA were 0.666, 0.730, 0.777, and 0.847 at 1, 3, 5, and 10 years, respectively. Adding SUA to the fully adjusted base model yielded modest improvements in discrimination and prediction error.

CONCLUSION

Among patients with T2DM, higher SUA levels were associated with an increased risk of incident, radiologically visible macrovascular calcification. SUA may help identify patients at higher risk of VC; however, the data-derived threshold of approximately 300 μmol/L should be considered exploratory and requires external validation. Whether lowering SUA reduces the risk of VC remains to be determined in prospective interventional studies.