Highlights• In a large study of male veterans, both low and high HDL cholesterol levels were associated with higher risks of dying prematurely compared with intermediate levels, forming a U-shaped curve. • The beneficial properties of HDL cholesterol were attenuated, but remained significant, in the presence of kidney disease.

Newswise — Washington, DC (August 11, 2016) — A new study indicates that maintaining an intermediate level of high density lipoprotein cholesterol (HDL-C) may help people live longer. The study, which appears in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN), found that both low and high HDL-C levels were linked with a higher risk of premature death. Also, intermediate HDL-C levels were associated with a lower risk of death across all levels of kidney function.

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 Benjamin Bowe, MPH and Ziyad Al-Aly, MD, FASN (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 Dr. 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.

Study co-authors include Yan Xie, MPH, Hong Xian, PhD, Sumitra Balasubramanian, MS, and Mohamed Zayed MD, PhD.

Disclosures: The authors reported no financial disclosures.

The article, entitled “High Density Lipoprotein Cholesterol and the Risk of All-cause Mortality among U.S. Veterans,” will appear online at http://www.cjasn.asnjournals.org/ on August 11, 2016, doi: 10.2215/CJN.00730116.

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doi: 10.2215/CJN.00730116