Combined Effect of Homocysteine and Uric Acid to Identify Patients With High Risk for Subclinical Atrial Fibrillation

Background Subclinical atrial fibrillation (SCAF) is often asymptomatic nonetheless harmful. In patients with cardiac implantable electronic devices, we evaluated the combined performance of homocysteine and uric acid (UA) biomarkers to discriminate high-risk patients for SCAF. Methods and Results We enrolled 1224 consecutive patients for evaluation of SCAF in patients with cardiac implantable electronic devices in Dalian, China, between January 2013 and December 2019. Clinical data and blood samples were obtained from patients selected according to the absence or presence of atrial high-rate episodes >6 minutes. Blood samples were obtained, and homocysteine and UA biomarkers were tested in all patients to distinguish their prognostic performance for SCAF. Homocysteine and UA biomarkers were significantly different in SCAF versus no SCAF. On multivariable Cox regression analysis with potential confounders, elevated homocysteine and UA biomarkers were significantly associated with an increased risk of SCAF. A rise of 1 SD in homocysteine (5.7 μmol/L) was associated with an increased risk of SCAF in men and women regardless of their UA levels. Similarly, a 1-SD increase in UA (91 μmol/L) was associated with an increased risk of SCAF among the patients with high levels of homocysteine in men (hazard ratio, 1.81; 95% CI, 1.43-2.30) and women (hazard ratio, 2.11; 95% CI, 1.69-2.62). The addition of homocysteine and UA to the atrial fibrillation risk factors recommended by the 2020 European Society of Cardiology Guidelines significantly improved risk discrimination for SCAF. Conclusions Homocysteine and UA biomarkers were strongly associated with SCAF. The prediction performance of the European Society of Cardiology model for SCAF was increased by the addition of the selected biomarkers. Registration URL: https://www.chictr.org.cn; Unique identifier: Chi-CTR200003837.