High Density Lipoprotein Cholesterol and the Risk of All-Cause Mortality among U.S. Veterans

Abstract

Background and objectives: The relationship between HDL cholesterol and all-cause mortality in patients with kidney disease is not clear. We sought to characterize the relationship of HDL cholesterol and risk of death and examine the association by eGFR levels.

Design, setting, participants, & measurements: We built a cohort of 1,764,986 men who were United States veterans with at least one eGFR between October of 2003 and September of 2004 and followed them until September of 2013 or death.

Results: Patients with low HDL cholesterol and low eGFR had a higher burden of comorbid illnesses. Over a median of 9.1 years (interquartile range, 7.7-9.4 years), 26,247 (40.1%), 109,222 (32.3%), 152,625 (29.2%), 113,785 (28.5%), and 139,803 (31.8%) participants with HDL cholesterol ≤25, >25 to <34, ≥34 to ≤42, >42 to <50, and ≥50 mg/dl died. In adjusted survival models, compared with the referent group of patients with low HDL cholesterol (≤25 mg/dl), intermediate HDL cholesterol levels (>25 to <34, ≥34 to ≤42, and >42 to <50 mg/dl) were associated with lower risk of death across all levels of eGFR. The lower risk was partially abrogated in those with high HDL cholesterol (≥50 mg/dl), and the risk of death was similar to the referent category among those with eGFR<30 or ≥90 ml/min per 1.73 m². Analysis by HDL cholesterol deciles and spline analyses suggest that the relationship between HDL cholesterol and death follows a U-shaped curve. There was a significant interaction between eGFR and HDL cholesterol in that lower eGFR attenuated the salutary association of HDL cholesterol and risk of death (P for interaction <0.01). Presence of coronary artery disease attenuated the lower risk of high HDL cholesterol and all-cause mortality in those with eGFR≥60 ml/min per 1.73 m² (P for interaction <0.05).

Conclusions: Our results show a U-shaped relationship between HDL cholesterol and risk of all-cause mortality across all eGFR categories. The risk is modified by eGFR and cardiovascular disease.

Keywords: Cardiovascular Diseases; Cholesterol, HDL; Epidemiology and outcomes; Humans; United States; Veterans; chronic kidney disease; coronary artery disease; hypercholesterolemia; lipids; mortality; mortality risk.