High-Density Lipoprotein As a Therapeutic Target: Clinical Evidence and Treatment Strategies

Sterling Rock Falls Clinic, Sterling, Illinois 61081-1252, USA.
The American Journal of Cardiology (Impact Factor: 3.28). 11/2005; 96(9A):50K-58K; discussion 34K-35K. DOI: 10.1016/j.amjcard.2005.08.008
Source: PubMed


The clinical importance of low serum levels of high-density lipoprotein (HDL) cholesterol is often under-recognized and underappreciated as a risk factor for premature atherosclerosis as well as for cardiovascular morbidity and mortality. Low serum levels of HDL are frequently encountered, especially in patients who are obese or have the metabolic syndrome. In prospective epidemiologic studies, every 1-mg/dL increase in HDL is associated with a 2% to 3% decrease in coronary artery disease risk, independent of low-density lipoprotein (LDL) cholesterol and triglyceride (TG) levels. The primary mechanism for this protective effect is believed to be reverse cholesterol transport, but several other anti-inflammatory, antithrombotic, and antiproliferative functions for HDL have also been identified. In recognition of these antiatherogenic effects, recent guidelines have increased the threshold for defining low levels of HDL for both men and women. The first step in achieving these revised targets is therapeutic lifestyle changes. When these measures are inadequate, pharmacotherapy specific to the patient's lipid profile should be instituted. Niacin therapy, currently the most effective means for raising HDL levels, should be initiated in patients with isolated low HDL (HDL <40 mg/dL, LDL and non-HDL at or below National Cholesterol Education Program (NCEP) targets based on global cardiovascular risk evaluation). Patients who have both low HDL and elevated LDL should receive a statin or statin-niacin combination therapy, and patients with concomitant low HDL and elevated TGs should receive a fibrate initially, with a statin, niacin, or ezetimibe added thereafter as needed to help attain NCEP lipoprotein targets.

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    • "The combination of a statin with NA can be an attractive option because both have excellent records of improving cardiovascular outcomes and can effectively correct all abnormalities of atherogenic dyslipidemia in patients with diabetes. A combination product containing extended-release NA and LV (Advicor®; Abbott Pharmaceutical Co., USA) is approved for the treatment of dyslipidemia(34). Over the last few years much attention has been paid in developing chromatographic, capillary electrophoresis (CE), and ion-exchange chromatographic methods for NA determination and its metabolites in human plasma and food(5–10). "
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    ABSTRACT: Most cardiovascular diseases need to be treated by more than a simple drug and the use of combination products diminishes noncompliance. Advicor(®) as a combination product of a vitamin and a fat lowering agent has no monograph in official pharmacopeias for its quality control purposes. In this study, first and third derivative signals for NA and LV quantitation at the two pairs of wavelengths, 261 and 273 nm; 245 and 249 nm were monitored with the addition of standard solutions of NA or LV, respectively. The limits of detection were 0.03 and 0.32 mg/L for LV and NA, respectively. The limits of quantitation were 0.09 and 0.78 mg/L for LV and NA, respectively. RSD% for both interday and intraday precision was lower than 2.6 and 2.7% for LV and NA, respectively. Selectivity of the method was assessed for both degradation products produced in stress conditions and common excipients that may present in the pharmaceutical dosage forms. The recommended procedure was successfully applied to real samples.
    Research in pharmaceutical sciences 04/2012; 7(2):95-102.
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    • "Adipose cells have been shown to bind to HDL [7], hence increased body fat may lead to an increased uptake of HDL particles from circulation resulting in a reduction in plasma HDL levels [8]. On the other hand, an increase in HDL has been associated with decreased risk of coronary artery disease [9], probably due to its role in the reverse cholesterol transport process where cholesterol in peripheral tissues is transported to the liver for reuse or bile acid synthesis, preventing the accumulation of cholesterol in the arteries [10]. HDL is also thought to be cardioprotective due to its antioxidant activity [11] "
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    ABSTRACT: This paper investigates the effects of very-low-calorie diets (VLCDs) used in the treatment of obesity on high-density lipoprotein (HDL) levels. Although the studies varied widely in their intervention format, duration, and baseline HDL levels, it would appear that HDL levels usually decrease during active weight loss using a VLCD, but these either return to pre-VLCD levels or improve overall during the weight-maintenance phase. More research needs to be done to determine optimal weight-maintenance programmes and the effects of VLCDs in the short term as well as on HDL levels in groups at increased risk of coronary heart disease.
    Cholesterol 01/2011; 2011(7, part 2):306278. DOI:10.1155/2011/306278
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    • "Numerous prospective cohort studies support a powerful inverse correlation between circulating HDL-cholesterol and coronary risk among patients with normal or elevated low-density lipoprotein- (LDL-) cholesterol [6, 7]. Low HDL-cholesterol levels increase the risk of coronary heart disease (CHD) and analysis of the largest US epidemiologic studies including the Framingham Heart Study, the Lipid Research Clinics (LRC) Primary Prevention Trial, the LRC Prevalence Mortality Followup Study, and the Multiple Risk Factor Intervention Trial (MRFIT) substantiated that, on average, each one (1) mg/dL increase in HDL-cholesterol reduces CHD risk by 2% in men and 3% decrease in women [8]. "
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    ABSTRACT: High-density lipoprotein (HDL) is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, as many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease. Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Further, numerous epidemiological studies have shown a protective association between HDL-cholesterol and cognitive impairment. Oxidative stress, including lipid peroxidation, has been shown to be the mediator of the pathologic effects of numerous risk factors of Alzheimer's disease. Lifestyle interventions proven to increase HDL- cholesterol levels including "healthy" diet, regular exercise, weight control, and smoking cessation have also been shown to provide neuro-protective effects. This review will focus on current knowledge of the beneficial effects of HDL-cholesterol as it relates to cardiovascular diseases, breast and lung cancers, non-Hodgkin's lymphoma, as well as its neuroprotective potential in reducing the risk of Alzheimer's disease and dementia.
    Cholesterol 01/2011; 2011(19):496925. DOI:10.1155/2011/496925
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