Aims Chronic kidney disease is a risk factor of the development of cardiovascular disease (CVD). However, it is not clear whether decline of glomerular filtration rate (GFR), not reduced GFR, is a risk factor for the incidence of CVD independent of proteinuria. Methods By using a population-based 521 123 person-years longitudinal cohort receiving annual health checkups from 2008 to 2010, we examined whether the annual decline of estimated GFR is a risk factor for CVD development independent of proteinuria. Results During the follow-up period, there were 12 041 newly developed CVD events, comprising 4426 stroke events and/or 8298 cardiac events. As expected, both reduced estimated GFR and proteinuria were risk factors for the development of CVD in our study population. Moreover, annual decline of estimated GFR was a significant and independent risk factor for the incidence of CVD (HR [95% CI], 1.23 [1.18-1.28] in males or 1.14 [1.10-1.18] in females for -10% per year) with covariant adjustment for proteinuria and reduced estimated GFR. Conclusion Annual decline of GFR is an independent risk factor for CVD. Serial measurement of both creatinine and proteinuria would be better to predict the incidence of CVD in the general population. Summary at a Glance Previous studies have shown that annual decline or increment estimated glomerular filtration rate may influence prognosis. This study focuses on the cardiovascular events and demonstrates that the annual decline rate in eGFR is a risk factor for cardiovascular events independent of proteinuria by using a large longitudinal Japanese population-based study of participants receiving annual health checkups from 2008-2010. To reduce the incidence of cardiovascular events in the general population, serial measurement of serum creatinine to obtain the change rate in eGFR is warranted.
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