Impact of changes in proteinuria on the risk of atrial fibrillation in patients with diabetes mellitus: a nationwide population-based study

Abstract Background Diabetes mellitus (DM) is a well-known risk factor for atrial fibrillation (AF). Proteinuria is also considered as an independent predictor for AF. However, there is limited data on whether the changes in proteinuria severity can impact the risk of AF among patients with DM. Purpose We aimed to evaluate the association between changes in proteinuria over time detected using a urine dipstick test and the risk of AF among patients with DM. Methods A total of 1,605,495 patients with DM who underwent two biennial health checkups provided by the National Health Insurance Service (NHIS) between January 2013 and December 2016 were included. All patients had two consecutive urine dipstick tests during the checkups. We divided the study population into four groups based on their glomerular filtration rate (GFR): > 90 ml/min, 60-90 ml/min, < 60 ml/min, and those with end-stage renal disease (ESRD). We evaluated the association between the changes in proteinuria over time detected using a urine dipstick test and the risk of AF and their changes by GFR. Results During a median 4.0-year follow-up, AF occurred in 32,391 persons (5.22 per 1,000 person-years). Among 1,605,495 patients who underwent two consecutive urine dipstick tests, 1,453,116 (90.51%) patients had a negative proteinuria on both tests (negative or trace result on both urine dipstick tests), and 68,979 (4.3%) patients had an aggravated proteinuria (from negative to more than 1+ result on subsequent urine dipstick test). While 48,357 (3.01%) patients had a resolved proteinuria (from positive to negative results on subsequent tests) and 35,043 (2.18%) patients had a persistent proteinuria (positive result on both tests). Those with aggravated or resolved or persistent proteinuria showed an increased risk of AF (HR 1.39, 95% CI 1.33-1.46; HR 1.37, 95% CI 1.30-1.45; HR 1.95, 95% CI 1.85-2.06) compared with most subjects who showed subsequent negative results on proteinuria. This result was consistent within every GFR group. However, the tendency of increment of AF risk by changes in proteinuria was more prominent in lower GFR groups (Table). In subgroup analysis, there was no significant difference between male and female. However, the younger aged (< 65 years) group had a more prominent tendency of increased AF risk by changes in proteinuria. Conclusion Changes in proteinuria showed a significant association with the risk of AF in patients with DM. This tendency was prominent in patients with lower GFR. Therefore, careful monitoring of AF risk based on proteinuria changes could be beneficial for those with DM.