High Cholesterol Predicts Lower Mortality in Dialysis Patients But Is Not Protective

Kidney dialysis patients with higher cholesterol levels die at a lower rate than those with lower cholesterol levels, which is opposite of the general public. However, a study by researchers at the John Hopkins Bloomberg School of Public Health determined that the lower mortality rate of those with higher cholesterol is likely due to the cholesterol-lowering effects of inflammation and malnutrition, two serious complications of kidney dialysis, and not a benefit of high cholesterol. The study is published in the January 28, 2004, edition of the Journal of the American Medical Association (JAMA).

“Using multiple blood tests we were able to show that the majority of dialysis patients have inflammation and/or malnutrition and these conditions distort the meaning of serum cholesterol. This explains why patients with lower cholesterol have higher mortality,” said Josef Coresh, MD, PhD, the study’s senior investigator and an associate professor in the Department of Epidemiology at the School. “We were able to show that when dialysis patients don’t have inflammation or malnutrition, higher cholesterol predicted a progressively higher risk of total and cardiovascular mortality. This is important since it undermines the idea that high cholesterol can be protective in dialysis patients and emphasizes the importance of cholesterol treatment,” explained Dr. Coresh.

The study included 823 dialysis patients from 79 clinics in the United States. Inflammation and/or malnutrition were detected by looking for abnormalities in any one of three laboratory tests (C-reactive protein, interleukin-6 or serum albumin) since any one test can miss patients with abnormalities. Participants with inflammation or malnutrition had lower cholesterol levels than those without either condition. Overall, higher cholesterol was incrementally associated with lower mortality, a finding which confirms other studies in dialysis patients and other sick populations such as smokers and the elderly. This opposite association from the expected higher mortality at higher cholesterol has led some physicians to avoid treating high cholesterol in dialysis patients. However, among patients without inflammation or malnutrition, higher cholesterol was strongly associated with higher mortality.

Yongmei Liu, MD, the study’s first author and a PhD candidate at the School, emphasized that the findings were similar when cardiovascular disease was the cause of death. Overall and among participants with inflammation or malnutrition cholesterol was not strongly related to cardiovascular mortality risk. However, among those without inflammation or malnutrition a strong association between higher cholesterol and higher risk was seen. “The same serum cholesterol means different things depending on the presence or absence of inflammation,” said Dr. Liu. “In dialysis patients, low serum cholesterol may signal the presence of poor nutritional status or chronic inflammation. Physicians should look for signs of inflammation and malnutrition which can be markers of high risk and distort the meaning of serum cholesterol. These findings are also relevant for other sick populations such as older patients and smokers.”

According to Dr. Coresh, “Cardiovascular disease is a leading cause of death for patients with kidney failure. Even though 30 percent of dialysis patients have unhealthy cholesterol levels fewer than 10 percent receive any cholesterol lowering medication. Our findings show that this population should be treated for high cholesterol.”

“Association Between Cholesterol and Mortality in Dialysis Patients, Role of Inflammation and Malnutrition” was written by Yongmei Liu, MD; Josef Coresh, MD, PhD; Joseph A. Eustace, MD, MHS; J. Craig Longenecker, MD, PhD; Bernard Jaar, MD, MPH; Nancy E. Fink, MPH; Russell P. Tracy, PhD; Neil R. Powe, MD, MPH, MBA; and Michael Klag, MD, MPH.

The study was funded by grants from the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association and the National Center for Research Resources.