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

INTRODUCTION: Oxidative 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. METHOD: We 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. RESULTS: During 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). CONCLUSION: Impaired anti-oxidant HDL function represents a strong and independent predictor of 30-day mortality as well as long-term mortality in critically ill patients.

Ethnicity and coronary artery disease: the role of high-density lipoprotein - a change in paradigm.

Cardiovascular disease (CVD) is the number one killer of men and women across ethnic groups in the USA. Health disparities in CVD, especially coronary artery disease (CAD), are well documented in the diverse American population. Despite efforts taken toward reducing cardiovascular health disparities, there are still gaps in its diagnosis and management. Current risk assessment guidelines consider high high-density lipoprotein (HDL) levels a protective factor against CAD, although its significance across races remains poorly understood. Recent clinical trials focused on increasing HDL levels have been disappointing. In this article, the authors have explored the role of HDL in CAD, have analyzed its significance across gender and ethnic groups and have challenged the broad application of widely used HDL level cutoffs in CAD risk assessment tools across these vulnerable groups. The current evidence suggests a paradigm change from HDL quantity to quality and function in future CVD risk research. This may better explain why some ethnic minority groups with a seemingly more benign lipid profile experience a higher CAD burden.

Laboratory assessment of HDL heterogeneity and function.

BACKGROUND: Plasma concentrations of HDL cholesterol (HDL-C) and its major protein component apolipoprotein (apo) A-I are strongly inversely associated with cardiovascular risk, leading to the concept that therapy to increase HDL-C and apoA-I concentrations would be antiatherosclerotic and protective against cardiovascular events. The recent failure of the drug torcetrapib, a cholesteryl ester transfer protein inhibitor that substantially increased HDL-C concentrations, has brought focus on the issues of HDL heterogeneity and function as distinct from HDL-C concentrations. CONTENT: This review addresses the current state of knowledge regarding assays of HDL heterogeneity and function and their relationship to cardiovascular disease. HDL is highly heterogeneous, with subfractions that can be identified on the basis of density, size, charge, and protein composition, and the concept that certain subfractions of HDL may be better predictors of cardiovascular risk is attractive. In addition, HDL has been shown to have a variety of functions that may contribute to its cardiovascular protective effects, including promotion of macrophage cholesterol efflux and reverse cholesterol transport and antiinflammatory and nitric oxide-promoting effects. SUMMARY: Robust laboratory assays of HDL subfractions and functions and validation of the usefulness of these assays for predicting cardiovascular risk and assessing response to therapeutic interventions are critically important and of great interest to cardiovascular clinicians and investigators and clinical chemists.

Family aggregation of high density lipoprotein cholesterol. Collaborative lipid research clinics program family study.

High density lipoprotein cholesterol data on a population-based random sample of 858 white and 72 black probands and their 3935 white and 205 black relatives were collected from nine North American clinics using a common protocol and standardized methodology. Familial associations were examined within clinics for whites and pooled across clinics for blacks. The influence of covariates and varying family size on correlations was examined using several sets of transformed and adjusted values and a variety of weighting schemes. Parent-offspring and sibling correlations were significant in most cases, but spouse correlations were not, suggesting a stronger influence of shared genes than shared environment on high density lipoprotein cholesterol. Adjustment for covariates tended to weaken the correlations, but the effect of variable family size was imperceptible. Although pairs involving pediatric offspring or siblings tended to show higher correlation than their adult counterparts, the differences were not significant. All correlations except father-daughter and brother-brother were homogeneous across clinics in whites. There was no asymmetry in parent-child correlations by the sex of the offspring, but the pooled mother-child correlation was significantly higher than father-child values, suggesting a possible maternal influence on high density lipoprotein cholesterol. No heterogeneity in correlations in high density lipoprotein cholesterol was detected between blacks and whites except for mother-son pairs.