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U-Shaped Relationship Between Proteinuria and High-Density Lipoprotein Cholesterol: Results of Cross-Sectional and
Manami Igata1, Kei Nakajima1,2,3
1School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, Yokosuka 238-8522, Japan.
Insights
Both low and very high levels of high-density lipoprotein cholesterol (HDL-C) are linked to proteinuria incidence. Body mass index (BMI) appears to play a significant role in this association.
Area of Science:
- Cardiovascular Health
- Nephrology
- Metabolic Syndrome
Background:
- High-density lipoprotein cholesterol (HDL-C) is typically considered protective against cardiovascular disease.
- However, exceptionally high HDL-C levels have been anecdotally linked to increased cardiovascular risk, with unclear mechanisms.
- Proteinuria, a marker of kidney damage, is a known predictor of cardiovascular disease.
Purpose of the Study:
- To investigate the association between serum HDL-C levels and the incidence of proteinuria.
- To explore the potential role of body mass index (BMI) in this relationship.
Main Methods:
- A large-scale, community-based study involving over 1.19 million participants aged 40-74 years.
- Cross-sectional analysis of proteinuria prevalence across 10 HDL-C categories.
- A 6-year prospective cohort study of 451,987 participants to assess proteinuria incidence based on baseline HDL-C and BMI.
Main Results:
- A U-shaped relationship was observed between HDL-C levels and proteinuria prevalence, with the lowest risk between 60-89 mg/dL.
- Logistic regression confirmed this U-shaped association, with the lowest odds ratio for proteinuria between 70-79 mg/dL.
- Very high HDL-C (≥90 mg/dL) showed a strengthened association with proteinuria after adjusting for BMI. The cohort study revealed a U-shaped incidence of proteinuria after adjusting for BMI.
Conclusions:
- Both low and very high serum HDL-C levels are associated with an increased risk of proteinuria.
- Body mass index (BMI) is identified as a significant contributing factor in the mechanism linking HDL-C levels to proteinuria.
- These findings suggest a complex, non-linear relationship between HDL-C and kidney health, potentially mediated by metabolic factors.
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.
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