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Lipid Lowering Drugs

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PanVascular Medicine

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Abstract

Fat is an important nutrient in our diets. The adverse cardiovascular events as a result of elevated levels of lipoproteins in the blood led to the concept of lipid-lowering medications. Non-statin agents such as niacin, fibrates, fish oils, and ezetimibe are well known as lipid-lowering agents. In various clinical trials such as WOSCOPS (West of Scotland Coronary Prevention Study), JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), and other trials, the concept of lowering of cholesterol-containing apolipoprotein B lipoproteins was achieved by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG Co A) reductase inhibitors or statins. Statins lower the LDL-C and thereby reduce cardiovascular morbidity and mortality. Many patients may not achieve their target levels of LDL-C, and as a result, there remains an LDL-associated residual risk. Loss-of-function mutations of the PCSK9 gene discovered were linked to low plasma LDL-C levels and a reduction of cardiovascular risk. In November of 2013, the American College of Cardiology (ACC) and American Heart Association (AHA) released four new guidelines such as Guideline on Risk Assessment, Guideline on Managing Blood Cholesterol, Guideline on Lifestyle Management, and Guideline for the Management of Overweight and Obesity which deal with the prevention of CVD by better assessing risk and by managing cholesterol, lifestyle, and weight. The central role of proprotein convertase subtilisin/kexin type 9 in the regulation of cholesterol homeostasis by increasing the endosomal and lysosomal degradation of hepatic LDLR (low-density lipoprotein receptor) has now been identified. Loss-of-function mutations of PCSK9 gene were reported to be linked to low plasma LDL-C levels and marked reduction of cardiovascular risk.

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Abbreviations

Low density lipoprotein (LDL):

Is the main carrier of plasma cholesterol and a major component of atherosclerotic plaque. It can be isolated by density gradient centrifugation.

LDL receptor:

Mosaic protein of 839 amino acids responsible for uptake of LDL.

ACC:

American College of Cardiology

ACCORD Study:

Effects of combination lipid therapy in type 2 diabetes mellitus

AFCAPS/TexCAPS:

Air Force/Texas Coronary Atherosclerosis Prevention Study

AHA:

American Heart Association

ARBITER 2 Trial:

Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended release niacin, an atherosclerosis progression in secondary prevention patients treated with statins

ASCOT-LLA:

Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm

ASCVD:

Atherosclerotic cardiovascular disease risk

COURAGE Trial:

Low levels of high-density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients. A post hoc analysis from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation)

CVD:

Cardiovascular disease

dal-OUTCOMES:

Effects of dalcetrapib in patients with a recent acute coronary syndrome

ENHANCE Trial:

Comparison of ezetimibe plus simvastatin vs. simvastatin monotherapy on atherosclerosis progression in familial hypercholesterolemia: design and rationale of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial

HMG Co:

A 3-hydroxy-3-methylglutaryl-coenzyme

JELIS Study:

Effects of EPA on coronary artery disease in hypercholesterolemia patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS)

JUPITER:

Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin

LDL-C:

Low-density lipoprotein cholesterol

LDLR:

Low-density lipoprotein receptor

MEGA:

Primary prevention of cardiovascular disease with pravastatin in Japan

MENDEL Study:

Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolemia (MENDEL): a randomized, double-blind, placebo-controlled, phase 2 study

OSLER Trial:

Efficacy and safety of long-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) Randomized trial

PCSK 9:

Proprotein convertase subtilisin/kexin type 9

Phospholipids:

Phospholipids are lipids containing, in addition to fatty acids and an alcohol, a phosphoric acid residue and a nitrogen containing base

SATURN:

Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin vs. Atorvastatin

siRNA:

Small interfering ribonucleic acid. Short (21–26 nucleotides) double-stranded RNAs that inhibit gene expression by directing destruction of complementary mRNAs; production of siRNA is triggered by double-stranded RNA

SREBP:

Sterol-responsive element-binding protein

Statins:

Statins are drugs which inhibit HMG-CoA reductase, thus upregulating LDL receptors

WOSCOPS:

West of Scotland Coronary Prevention Study

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Authors and Affiliations

  1. Departments of Pathology and Pharmacology, Loyola University Health System, Maywood, IL, USA

    Jawed Fareed

  2. Departments of Pathology and Ophthalmology, Loyola University Health System, Maywood, IL, USA

    Omer Iqbal

  3. Department of Pathology, Loyola University Health System, Maywood, IL, USA

    Daneyal Syed

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  1. Omer Iqbal
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  2. Daneyal Syed
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  3. Jawed Fareed
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Correspondence to Daneyal Syed .

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  1. Division of Cardiovascular Disease Department of Internal Medicine, Health Care Center Bitterfeld, Bitterfeld-Wolfen, Germany

    Peter Lanzer

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Iqbal, O., Syed, D., Fareed, J. (2015). Lipid Lowering Drugs. In: Lanzer, P. (eds) PanVascular Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37078-6_220

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