Statin Treatment Improves Plasma Lipid Levels but not HDL Subclass Distribution in Patients Undergoing Percutaneous Coronary Intervention.
ABSTRACT Despite the established efficacy of statin therapy, the risk of cardiovascular events remains high in many patients. We examined high-density lipoprotein (HDL) subclass distribution profiles among statin-treated coronary heart disease (CHD) patients undergoing percutaneous coronary intervention (PCI). Plasma HDL subclasses were measured in 85 patients with established CHD and quantified by two-dimensional gel electrophoresis and immunoblotting. In CHD patients with statin treatment, the mean value of total cholesterol (TC) reached the desirable level and the triacylglycerol level (TAG) was borderline high. Moreover, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoproteinA-I, and apolipoproteinB-100 levels in these patients resembled those in normolipidemic healthy subjects. The HDL subclass did not show a normal distribution and was characterized by the lower large-sized HDL(2b) contents and higher contents of small-sized preβ(1)-HDL in CHD patients, compared to those in normolipidemic control subjects. Multiple stepwise regression analysis revealed that the severity of coronary stenosis, determined by the Gensini Score, was significantly and independently predicted by HDL(2b) and HDL(3b). Statin therapy was effective in modifying plasma lipids levels, but not adequate as a monotherapy to normalize the HDL subclass distribution phenotype of patients with CHD undergoing PCI. The HDL subclass distribution may aid in risk stratification, especially in patients with CHD and therapeutic LDL-C and HDL-C levels.
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ABSTRACT: Elevated serum cholesterol concentrations in mid-life increase risk for Alzheimer's disease (AD) in later life. However, lower concentrations of cholesterol-carrying high density lipoprotein (HDL) and its principal apolipoprotein A1 (ApoA1) correlate with increased risk for AD. As HDL transports oxocarotenoids, which are scavengers of peroxynitrite, we have investigated the hypothesis that lower HDL and oxocarotenoid concentrations during AD may render HDL susceptible to nitration and oxidation and in turn reduce the efficiency of reverse cholesterol transport (RCT) from lipid-laden cells. Fasting blood samples were obtained from subjects with 1) AD without cardiovascular comorbidities and risk factors (AD); 2) AD with cardiovascular comorbidities and risk factors (AD Plus); 3) normal cognitive function; for carotenoid determination by HPLC, analysis of HDL nitration and oxidation by ELISA, and 3H-cholesterol export to isolated HDL. HDL concentration in the plasma from AD Plus patients was significantly lower compared to AD or control subject HDL levels. Similarly, lutein, lycopene, and zeaxanthin concentrations were significantly lower in AD Plus patients compared to those in control subjects or AD patients, and oxocarotenoid concentrations correlated with Mini-Mental State Examination scores. At equivalent concentrations of ApoA1, HDL isolated from all subjects irrespective of diagnosis was equally effective at mediating RCT. HDL concentration is lower in AD Plus patients' plasma and thus capacity for RCT is compromised. In contrast, HDL from patients with AD-only was not different in concentration, modifications, or function from HDL of healthy age-matched donors. The relative importance of elevating HDL alone compared with elevating carotenoids alone or elevating both to reduce risk for dementia should be investigated in patients with early signs of dementia.Journal of Alzheimer's disease: JAD 01/2014; 40(2). DOI:10.3233/JAD-131964 · 4.15 Impact Factor