Impaired High-Density Lipoprotein Anti-Oxidant Function Predicts Poor Outcome in Critically Ill Patients

Abstract

IntroductionOxidative stress affects clinical outcome in critically ill patients. Although high-density lipoprotein (HDL) particles generally possess anti-oxidant capacities, deleterious properties of HDL have been described in acutely ill patients. The impact of anti-oxidant HDL capacities on clinical outcome in critically ill patients is unknown. We therefore analyzed the predictive value of anti-oxidant HDL function on mortality in an unselected cohort of critically ill patients.MethodWe prospectively enrolled 270 consecutive patients admitted to a university-affiliated intensive care unit (ICU) and determined anti-oxidant HDL function using the HDL oxidant index (HOI). Based on their HOI, the study population was stratified into patients with impaired anti-oxidant HDL function and the residual study population.ResultsDuring a median follow-up time of 9.8 years (IQR: 9.2 to 10.0), 69% of patients died. Cox regression analysis revealed a significant and independent association between impaired anti-oxidant HDL function and short-term mortality with an adjusted HR of 1.65 (95% CI 1.22–2.24; p = 0.001) as well as 10-year mortality with an adj. HR of 1.19 (95% CI 1.02–1.40; p = 0.032) when compared to the residual study population. Anti-oxidant HDL function correlated with the amount of oxidative stress as determined by Cu/Zn superoxide dismutase (r = 0.38; p<0.001).ConclusionImpaired anti-oxidant HDL function represents a strong and independent predictor of 30-day mortality as well as long-term mortality in critically ill patients.

Impaired High‐Density Lipoprotein Anti‐Oxidative Function Is Associated With Outcome in Patients With Chronic Heart Failure

“…So far, antioxidative properties of HDL have been found impaired in common CHF-related comorbidities such as chronic kidney disease and type 2 diabetes mellitus, and determination of the HOI turned out to be a useful predictor of cardiovascular events and mortality in patients with acute coronary syndrome. 13,15,33,34 With respect to CHF, a previously conducted case-control study has reported reduced HDL antioxidative capacity in patients with ischemic CHF. 16 The present study extends this initial observation, showing that an impaired HDL antioxidative capacity is associated with higher mortality in CHF patients independent of traditional cardiovascular risk factors and irrespective of the underlying etiology.…”

“…So far, antioxidative properties of HDL have been found impaired in common CHF‐related comorbidities such as chronic kidney disease and type 2 diabetes mellitus, and determination of the HOI turned out to be a useful predictor of cardiovascular events and mortality in patients with acute coronary syndrome . With respect to CHF, a previously conducted case‐control study has reported reduced HDL antioxidative capacity in patients with ischemic CHF .…”

Research update for articles published in EJCI in 2015

“…Furthermore, there is increasing evidence that oxidative stress dramatically increases during critical illness. Contemporary data in a cohort of 270 intensive care unit (ICU) patients revealed a strong association between survival and antioxidant HDL function [3]. The results of this study suggest that restoration and maintenance of antioxidant HDL capacity might serve as a new therapeutic target in critically ill patients and considering the persistent effect of impaired antioxidant HDL function on clinical outcome, high-risk patients might benefit from specific treatment.…”

Comparing fluorescence-based cell-free assays for the assessment of antioxidative capacity of high-density lipoproteins

“…A number of studies using the DCF assay have demonstrated that patients with chronic inflammatory diseases have lower antioxidative capacity (higher DCF values, expressed as HII) compared to healthy subjects [ 15 – 17 ]. Recently, it has also been reported that higher HII values are associated with increased mortality in critically ill patients [ 18 ]. On the other hand, another study has shown that, while acute coronary syndrome patients had significantly higher than normal HII values, no differences were observed between chronic CHD patients and healthy subjects [ 5 ].…”