Intermediate high-density lipoprotein cholesterol levels may help people have a longer life, finds a new study published in the Clinical Journal of the American Society of Nephrology.

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Low and high levels of HDL cholesterol increase the risk, while intermediate HDL cholesterol levels decrease the risk of premature death.

Cholesterol is a waxy, fat-like substance that the body needs to help build cells; it is carried through the bloodstream and attaches to proteins called lipoproteins.

If blood vessels are damaged, cholesterol can be deposited, eventually causing narrowings. People with kidney disease are more likely to have problems with narrowings in their blood vessels than healthy people.

High-density lipoprotein (HDL) is known as the "good" cholesterol due to the way it assists with removing excess cholesterol from the bloodstream and taking it to the liver, where it is broken down and removed from the body. Higher levels of HDL cholesterol are linked to a lower risk of heart disease, heart attacks, and stroke.

Patients with kidney disease often have lower HDL cholesterol levels, which could account for their higher risk of early death. The research team aimed to investigate the relationship between HDL cholesterol levels and premature death in kidney disease patients.

Benjamin Bowe, M.P.H., of Washington University School of Medicine, and Ziyad Al-Aly, M.D., FASN, of Veterans Affairs Saint Louis Health Care System, and colleagues retrospectively studied 1,764,986 American male veterans.

Participants were chosen who had at least one measurement of kidney function and one measure of HDL cholesterol between October 2003 and September 2004, and they were followed until September 2013 or death.

U-shaped relationship between HDL cholesterol levels and risk of death

According to the Centers for Disease Control and Prevention (CDC), desirable levels of HDL cholesterol should be around 40 mg/dL or above.

However, findings from the study indicate that both low HDL cholesterol levels less than 25 mg/dL and high HDL cholesterol levels above 50 mg/dL were linked to an increased risk of premature death during follow-up. While intermediate levels between 25-50 mg/dL reduced the risk of early death, thus forming a U-shaped relationship between HDL cholesterol and mortality risk.

In the presence of kidney disease, the beneficial properties of intermediate HDL cholesterol levels were not as strong, but they remained significant.

"The finding that high HDL cholesterol 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," says 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 adds.

He notes that a Big Data approach to the investigation allows a more refined examination of the relationship between HDL cholesterol and risk of death across the full spectrum of HDL cholesterol levels.

"Our findings may explain why clinical trials aimed at increasing HDL cholesterol levels have failed to show improvement of clinical outcomes."

Benjamin Bowe, M.P.H.

In a previous study, Bowe and Al-Aly found that low levels of HDL cholesterol increase the risk of incident kidney disease and its progression.

Read about how HDL cholesterol may not protect against heart disease.