Semiquantitative assessed proteinuria and risk of heart failure: Analysis of a nationwide epidemiological database.

BACKGROUND Heart failure (HF) is increasing in prevalence worldwide. We explored whether adults with trace and positive proteinuria were at a high risk for incident HF compared with those with negative proteinuria using a nationwide epidemiological database. METHODS This is an obserevational cohort study using the JMDC Claims Database collected between 2005 and 2020. This is a population-based sample (n = 1,021,943; median age [interquartile range], 44 [37-52] years; 54.8% men). No participants had a known history of cardiovascular disease. Each participant was categorized into three groups according to the urine dipstick test results: negative proteinuria (n = 902,273), trace proteinuria (n = 89,599), and positive proteinuria (≥1+) (n = 30,071). The primary outcome was HF. The secondary outcomes were myocardial infarction, stroke, and atrial fibrillation. We performed multivariable Cox regression analyses to identify the association between the proteinuria category and incient HF and other cardiovascular disease events. RESULTS Over a mean follow-up of 1,150 ± 920 days, 17,182 incident HF events occurred. After multivariable adjustment, hazard ratios (HRs) for HF events were 1.09 (95% confidence interval [CI], 1.03-1.15) and 1.59 (95% CI, 1.49-1.70) for trace proteinuria and positive proteinuria vs. negative proteinuria, respectively. This association was present irrespective of clinical characteristics. A stepwise increase in the risk of myocardial infarction, stroke, and atrial fibrillation with proteinuria category was also observed. Our primary results were confirmed in participants after multiple imputation for missing values and in those having no medications for hypertension, diabetes mellitus, and dyslipidemia. Discriminative predictive value for HF events improved by adding the results of urine dipstick test to traditional risk factors (net reclassification improvement 0.0497, 95% CI 0.0346-0.0648, p < 0.001). CONCLUSIONS Not only positive proteinuria but also trace proteinuria was associated with a greater incidence of HF in the general population. Semiquantitative assessment of proteinuria would be informative for the risk stratification of HF.