A highly significant association (p < 0.001) was found in 1971-1972 between pre-beta-1 lipoprotein and coronary heart disease. Later, pre-beta-1 lipoprotein was in fasting serum samples found to be equivalent to Lp(a) lipoprotein. Continuing structural and clinical studies further documented the high atherogenicity of Lp(a) and revealed probable pathogenetic mechanisms. Interest in Lp(a) has increased tremendously during the last few years due to the recent overwhelming support for an independent association between Lp(a) and atherosclerotic disorders and the revelations of its fascinating structure. The structure of Lp(a), its association with clinical disorders and probable pathogenetic mechanisms are exemplified and discussed in relation to type of developed atheromas, their susceptibility to disruption and the importance of inherited high Lp(a) levels for the thrombotic complications.
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Inclusion of Almonds in a Cholesterol-Lowering Diet Improves Plasma HDL Subspecies and Cholesterol Efflux to Serum in Normal-Weight Individuals with Elevated LDL Cholesterol.
J Nutr
August 2017
Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA
: Almonds may increase circulating HDL cholesterol when substituted for a high-carbohydrate snack in an isocaloric diet, yet little is known about the effects on HDL biology and function. The objective was to determine whether incorporating 43 g almonds/d in a cholesterol-lowering diet would improve HDL subspecies and function, which were secondary study outcomes. In a randomized, 2-period, crossover, controlled-feeding study, a diet with 43 g almonds/d (percentage of total energy: 51% carbohydrate, 16% protein, and 32% total and 8% saturated fat) was compared with a similar diet with an isocaloric muffin substitution (58% carbohydrate, 15% protein, and 26% total and 8% saturated fat) in men and women with elevated LDL cholesterol.
View Article and Find Full Text PDFA single infusion of MDCO-216 (ApoA-1 Milano/POPC) increases ABCA1-mediated cholesterol efflux and pre-beta 1 HDL in healthy volunteers and patients with stable coronary artery disease.
Eur Heart J Cardiovasc Pharmacother
January 2016
The Medicines Company (Schweiz) GmbH , Zürich , Switzerland.
Aims: Apolipoprotein A-1 (ApoA-1), based on epidemiology, is inversely associated with cardiovascular (CV) events. Human carriers of the ApoA-1 Milano variant have a reduced incidence of CV disease. Regression of atherosclerotic plaque burden was previously observed on intravascular ultrasound (IVUS) with ETC-216, a predecessor of MDCO-216.
View Article and Find Full Text PDFCholesterol Efflux Capacity and Pre-Beta-1 HDL Concentrations Are Increased in Dyslipidemic Patients Treated With Evacetrapib.
J Am Coll Cardiol
November 2015
Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:
Background: Potent cholesteryl ester transfer protein (CETP) inhibitors have been shown to substantially increase high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I levels as monotherapy and combined with statins. However, data on the effects of this class of drugs on macrophage cholesterol efflux capacity (CEC), a functional assay that characterizes a key step in the process of reverse cholesterol transport, are limited.
Objectives: This study assessed the impact of evacetrapib, statins, or combination therapy on CEC.
Analysis of "On/Off" Kinetics of a CETP Inhibitor Using a Mechanistic Model of Lipoprotein Metabolism and Kinetics.
CPT Pharmacometrics Syst Pharmacol
August 2015
Roche Pharma Research and Early Development, Clinical Pharmacology, Roche Innovation Center Basel, F. Hoffmann-La Roche Basel, Switzerland.
RG7232 is a potent inhibitor of cholesteryl-ester transfer protein (CETP). Daily oral administration of RG7232 produces a dose- and time-dependent increase in high-density lipoprotein-cholesterol (HDL-C) and apolipoproteinA-I (ApoA-I) levels and a corresponding decrease in low-density lipoprotein-cholesterol (LDL-C) and apolipoproteinB (ApoB) levels. Due to its short plasma half-life (∼3 hours), RG7232 transiently inhibits CETP activity during each dosing interval ("on/off" kinetics), as reflected by the temporal effects on HDL-C and LDL-C.
View Article and Find Full Text PDFHDL deficiency due to a new insertion mutation (ApoA-INashua) and review of the literature.
J Clin Lipidol
August 2013
Division of Endocrinology and Metabolism, Tufts Medical Center, Boston, MA, USA.
A 61-year-old white man of European ancestry with significant coronary heart disease since age 42 years and marked high-density lipoprotein (HDL) deficiency (HDL cholesterol 1 mg/dL) was evaluated. His fasting low-density lipoprotein cholesterol level was 42 mg/dL, and his triglycerides were 417 mg/dL on therapy with rosuvastatin 40 mg/day, ezetimibe 10 mg/day, fenofibrate 145 mg/day, and extended-release niacin 2 g/day. Further analysis of his plasma revealed an apolipoprotein (apo) A-I level of 23.
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