Low HDL Level Indicates Poor Prognosis for Sepsis


DES PLAINES, Ill. -- Critically ill patients with low blood levels of high-density-lipoprotein (HDL) cholesterol, or good cholesterol, on the first day of severe sepsis have a higher mortality rate according to an article in the August issue of Critical Care Medicine.
"Our study revealed that people with an HDL cholesterol level of <20 mg/dL on day one of severe sepsis were almost 13 times more likely to die within 30 days than those who had a higher HDL level," said co-author Chong-Jen Yu, MD, PhD, of the department of internal medicine at National Taiwan University Hospital and National Taiwan University Medical College in Taipei, Taiwan. "These people also tended to have higher serum cytokines, stayed longer in ICU, contracted hospital-acquired infection and required more life support." Sepsis is the leading cause of death in critically ill patients, and it is fatal for 30 percent to 50 percent of them. Lipoproteins, a family of proteins in human blood that normally bind to lipids, have been found to bind and neutralize toxic germ products, and, therefore, might be beneficial to patients with sepsis.
The researchers measured serum levels of lipids and lipoproteins of 63 patients in the intensive care unit (ICU) of a 2,000-bed, tertiary-level university hospital on the first day of severe sepsis and continued to monitor them for the next 14 days. Patients all met the criteria for severe sepsis as defined by the 1991 American College of Chest Physicians/Society of Critical Care Medicine consensus conference.
The investigators found that patients who on the first day of sepsis had an HDL cholesterol level less than 20mg/dL and apolipoprotein A-1 less than 100mg/dL had a higher rate of overall and sepsis-attributable 30-day mortality. Apolipoproteins are the proteins that deliver fats through the blood. These patients also had an increased risk of prolonged ICU stays (greater than seven days) and hospital-acquired infections.
Although this study appears to help predict the prognosis in severe sepsis, the researchers went on to conduct a cell culture study where they found that a treatment with HDL after the commencement of sepsis was not helpful.
It is not clear whether a lower HDL level in septic patients is only a "bystander phenomenon" or directly causes death by sepsis. It is also unclear whether the HDL levels were already low before sepsis, or consumed by higher amounts of germ toxin, or by the suppression of production by host cytokines.
"We speculated that strategies to achieve a higher HDL cholesterol level before the start of severe sepsis might improve survival rates. Further studies performed with prospective and randomized designs are needed to work out potential therapeutic strategies to achieve high HDL level," said Yu.
The authors concluded that further studies performed with prospective and randomized designs are needed to demonstrate the therapeutic benefits of HDL and its role in sepsis.
In an accompanying editorial, Hobart W. Harris, MD, MPH, notes that the findings in this study are similar to those of previous researchers, but that this one has some important differences. "In the current report, total serum cholesterol levels were not only identical between survivors and non-survivors, but were stable during the 14-day study period. In contrast, HDL cholesterol concentrations did yield a more variable pattern, with levels that were low for the first four days but returned to normal at one week."
Harris, of the department of surgery at the University of California, San Francisco, adds, "The mechanisms governing sepsis-induced changes in lipid metabolism and how lipoproteins protect against infection are incompletely understood." Due to the serious clinical problems that sepsis poses, he concludes that "novel approaches to the treatment of sepsis are essential."
Source: Society of Critical Care Medicine





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