Pro-oxidant HDL predicts poor outcome in patients with ST-elevation acute coronary syndrome

Abstract

Oxidative stress affects clinical outcome in patients with ST-elevation acute coronary syndrome (STE-ACS). Although high-density lipoprotein (HDL) particles are generally considered protective, deleterious properties of HDL have been observed in patients with acute myocardial infarction. Here, we analysed the association between pro-oxidant HDL and all-cause mortality in STE-ACS patients. We determined the antioxidant function of HDL in 247 prospectively enrolled patients undergoing primary percutaneous coronary intervention for STE-ACS. Patients were stratified as by a pro-oxidant serum HDL oxidant index (HOI≥ 1) or with an antioxidant serum HOI (HOL< 1) capacity. Multivariate regression analysis was used to relate HOI to survival. The median follow-up time was 23 months (IQR 14.4-40.0 months). Pro-oxidant HDL was observed in 44.1 % of STE-ACS patients and was independently associated with all-cause mortality with a hazard ratio of 3.30(95 %CI 1.50-7.27, p = 0.003). Mortality rates were higher in patients with baseline pro-oxidant HDL compared to patients with preserved HDL function at 30 days (11.9 % vs 2.2 %, p=0.002), and at 4 years (22.9 % vs 8.7 %, p=0.002). Elevated neutrophil counts were a strong and independent predictor for pro-oxidant HDL with an odds ratio per standard deviation of 1.50 (95 %CI 1.11-2.03, p=0.008), as was history of prior acute myocardial infarction, elevated triglycerides levels and reduced glomerular filtration rate. In conclusion, pro-oxidant HDL represents a strong and independent predictor of long-term as well as short-term all-cause mortality in STE-ACS patients. Elevated neutrophil counts predicted the presence of serum pro-oxidant HDL. The maintenance of HDL functions might be a promising therapeutic target in STE-ACS 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 . With respect to CHF, a previously conducted case‐control study has reported reduced HDL antioxidative capacity in patients with ischemic CHF .…”

“…Samples were stored at −80°C and used for further analyses immediately after thawing. HDL antioxidative capacity, the ability of HDL to inactivate previously oxidized LDL, was measured using a well‐validated cell‐free assay comparable to the cell‐based assays as previously described . The assay is based on the conversion of 2′,7′‐dichlorodihydrofluorescein diacetate (DCF) into its fluorescent form in the presence of oxidized LDL.…”

“…The high‐density oxidative index (HOI) was determined by calculating the ratio of fluorescence in the presence of apo‐B‐depleted patient samples divided by the fluorescence of oxidized LDL alone and log‐transformed before analysis. A HOI <1.0 stands for antioxidative HDL function, whereas a HOI ≥1.0 indicates pro‐oxidative HDL . This definition is based on the functional properties of HDL and describes whether the respective apo‐B‐depleted patient sample attenuates or aggravates experimental oxidative stress.…”

“…Thus, HDL is believed to play an important role in diminishing elevated oxidative stress levels. However, it has become evident that protective properties of HDL become functionally impaired under certain conditions such as inflammation and tissue injury, and oxidatively modified HDL may even promote pro‐oxidative processes . A previously conducted case‐control study published by Patel et al showed an inverse correlation between the prevalence of CHF and the ability of HDL to promote reverse cholesterol transport or to prevent lipid oxidation .…”

“…However, it has become evident that protective properties of HDL become functionally impaired under certain conditions such as inflammation and tissue injury, and oxidatively modified HDL may even promote pro-oxidative processes. [9][10][11][12][13][14][15] A previously conducted case-control study published by Patel et al showed an inverse correlation between the prevalence of CHF and the ability of HDL to promote reverse cholesterol transport or to prevent lipid oxidation. 16 In addition, paraoxonase-1 (PON-1) activity, which represents an HDL-bound key mediator to prevent oxidative modifications, has previously been linked to outcome in CHF.…”