Intermediate HDL-C levels lower kidney disease mortality risk

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Maintaining an intermediate level of high-density lipoprotein cholesterol (HDL-C) is associated with a lower risk of death across all levels of kidney function, found a large epidemiological analysis.

The study found that both low and high levels of high-density lipoprotein cholesterol (HDL-C) were linked with a higher risk of premature death.

Patients with kidney disease often have reduced levels of HDL-C, which may partly explain their higher risk of dying prematurely; however, the relationship between HDL-C and premature death in patients with kidney disease is unclear. To investigate, a team led by Dr Benjamin Bowe and Dr Ziyad Al-Aly, (Washington University School of Medicine and VA Saint Louis Health Care System) retrospectively studied 1,764,986 US male veterans with at least one measurement of kidney function and one measure of HDL-C between October 2003 and September 2004. Participants were followed until September 2013.

The researchers found that both low and high HDL-C levels were associated with higher risks of dying during follow-up compared with intermediate HDL-C levels, forming a U-shaped relationship between HDL-C and mortality risk. The beneficial properties of intermediate levels of HDL-C were attenuated, but remained significant, in the presence of kidney disease.

“The finding that high HDL-C was also associated with higher risk of death was not expected and has not been reported previously in large epidemiologic studies such as the Framingham Heart Study and others,” said Al-Aly. “Prior epidemiologic studies significantly advanced our understanding of the relationship between cholesterol parameters and clinical outcomes; however, these studies are limited in that the number of patients in these cohorts is relatively small compared with the current Big Data approach.”

He noted that a Big Data approach allows a more nuanced examination of the relationship between HDL-C and risk of death across the full spectrum of HDL-C levels. “Our findings may explain why clinical trials aimed at increasing HDL-C levels have failed to show improvement of clinical outcomes,” noted Bowe.

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 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.

Benjamin Bowe, Yan Xie, Hong Xian, Sumitra Balasubramanian, Mohamed A Zayed, Ziyad Al-Aly

American Society of Nephrology abstract
Clinical Journal of the American Society of Nephrology abstract

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