Risk of cardiovascular disease associated with repeated proteinuria across annual kidney function screening among the middle-aged and older general population in Japan: a retrospective cohort study.

Objectives: We aimed to investigate the association between repetitive proteinuria and cardiovascular events among the middle-aged and older general Japanese population.

Design: Retrospective cohort study.

Setting: We used repeated health screening results and medical claim data from one of the largest health insurers in Japan.

Participants: Among the middle-aged and older participants (40-74 years, n=179 840), 90 752 were excluded for undergoing health screening fewer than two times and 344 were excluded for having a history of cardiovascular diseases; 88 744 who underwent kidney function screenings at least two times (from April 2011 to March 2015) were included in the analysis. Based on dipstick proteinuria test results, the participants were divided into 'Repetitively-positive' (positive two times or more (positive proteinuria was defined as≥1+)), 'Once-positive' and 'All-negative' groups.

Primary And Secondary Outcome Measures: The primary outcome of major cardiovascular events from baseline screening to June 2021 was hospitalisation or death due to acute myocardial infarction (AMI), cerebrovascular diseases, heart failure (HF) or peripheral vascular diseases (PVDs). The association between proteinuria and major cardiovascular events was assessed using a Cox proportional hazards model.

Results: Of the 88 744 participants, 8775 (9.9%) and 5498 (6.2%) had Once-positive and Repetitively-positive proteinuria, respectively. During the follow-up period of 402 799 person-years (median 5.25 years), 660 cardiovascular events were observed, with an incidence of 1.64 per 1000 person-years (95% CI 1.52 to 1.77). Despite adjusting for major cardiovascular risk factors, we observed a high incidence of cardiovascular events in the Repetitively-positive (HR 2.08, 95% CI 1.67 to 2.59) and Once-positive groups (HR 1.36, 95% CI 1.07 to 1.72). We found similar associations for AMI, cerebrovascular disease, HF and PVD.

Conclusions: Proteinuria is often repeatedly detected during annual renal screening in the general population. Repetitive proteinuria is a risk factor for major cardiovascular events.