Association of High-Density Lipoprotein Cholesterol With GFR Decline in a General Nondiabetic Population

Introduction: Although lower high-density lipoprotein cholesterol (HDL-C) levels are considered a risk factor for cardiovascular disease (CVD), experimental evidence suggest that aging, inflammation, and oxidative stress may remodel HDL-C, leading to dysfunctional HDL-C. Population studies on HDL-C and loss of the glomerular filtration rate (GFR) reported inconsistent results, but they used inaccurate estimates of the GFR and may have been confounded by comorbidity. Methods: We investigated the association of HDL-C levels with risk of GFR loss in a general population cohort; the participants were aged 50-62 years and did not have diabetes, CVD, or chronic kidney disease (CKD) at baseline. The GFR was measured using iohexol-clearance at baseline (n=1627) and at the followup (n=1324) after a median of 5.6 years. We also investigated any possible effect modification by lowgrade inflammation, physical activity, and sex. Results: Higher HDL-C levels were associated with steeper GFR decline rates and increased risk of rapid GFR decline (>3 ml/min per 1.73 m2 per year) in multivariable adjusted linear mixed models and logistic regression (-0.64 ml/min per 1.73 m2 per year [95% CI -0.99, -0.29; P < 0.001] and odds ratio 2.7 [95% CI 1.4, 5.2; P < 0.001] per doubling in HDL-C). Effect modifications indicated a stronger association between high HDL-C and GFR loss in physically inactive persons, those with low-grade inflammation, and men. Conclusion: Higher HDL-C levels were independently associated with accelerated GFR loss in a general middle-aged nondiabetic population.