U-Shaped Relationship Between Proteinuria and High-Density Lipoprotein Cholesterol: Results of Cross-Sectional and Six Years Cohort Studies (KITCHEN-10)

BACKGROUND: Although a very high level of high-density lipoprotein cholesterol (HDL-C) may be a potential cardiovascular disease risk factor, the detail and underlying mechanism remain unclear. Therefore, we examined the associations of serum HDL-C with the incidence of proteinuria, a predictor for cardiovascular disease, in a community-based study. METHODS: We investigated clinical parameters, including serum HDL-C and proteinuria, among 1,191,409 people aged 40 - 74 years who underwent a health checkup in a cross-sectional study. In the cohort study, the incidence of proteinuria after 6 years was investigated in 451,987 participants without proteinuria at baseline, who were simultaneously enrolled in the cross-sectional study. RESULTS: The prevalence of proteinuria showed a U-shaped relationship with 10 HDL-C categories, with a minimum of 60 - 89 mg/dL in the cross-sectional study. Logistic regression analysis showed similar U-shaped relationships between odds ratios for proteinuria and HDL-C categories, with a minimum of 70 - 79 mg/dL. The associations between very high HDL-C (≥ 90 mg/dL) and proteinuria were strengthened after adjustment for body mass index (BMI). In the cohort study, a crude L-shaped relationship was observed between the incidence of proteinuria and baseline HDL-C, which turned into U-shaped relationship after adjustment for baseline BMI and HDL-C after 6 years. CONCLUSIONS: Low and very high levels of HDL-C may be associated with the incidence of proteinuria, and BMI may be a potent contributing factor to the underlying mechanism.