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Eruptive xanthomas on the back of a patient admitted with a triglyceride level of 4600 mg/dL and acute pancreatitis.
Close-up of eruptive xanthomas.
Composition of triglyceride (TG)-rich lipoproteins. IDL = intermediate-density lipoprotein; VLDL = very low-density lipoprotein.
Lipoprotein lipase (LPL) releases free fatty acids (FFAs) from chylomicrons (chylo) and produces chylomicron remnants that are small enough to take part in the atherosclerotic process. Chol = cholesterol; TGs, TGS = triglycerides.
Once very low-density lipoprotein (VLDL) has been metabolized by lipoprotein lipase, VLDL remnants in the form of intermediate-density lipoprotein (IDL) can be metabolized by hepatic lipase, producing low-density lipoprotein (LDL), or they can be taken up by the LDL receptor via either apolipoprotein B (apo B) or apo E. Chol = cholesterol; TGs = triglycerides.

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Table 1. Fredrickson Classification of Hyperlipidemia

Type	Serum Elevation	Lipoprotein Elevation
I	Cholesterol and triglycerides	Chylomicrons
IIa	Cholesterol	LDL
IIb	Cholesterol and triglycerides	LDL, VLDL
III	Cholesterol and triglycerides	IDL
IV	Triglycerides	VLDL
V	Cholesterol and triglycerides	VLDL, chylomicrons
IDL = intermediate-density lipoprotein; LDL = low-density lipoprotein; VLDL = very low-density lipoprotein. Source: Fredrickson DS, Lees RS. A system for phenotyping hyperlipidaemia. Circulation. Mar 1965;31:321-7.^[3]

Table 2. Classification of Triglycerides

Classification	TG level, mg/dL
Normal triglyceride level	< 150
Borderline-high triglyceride level	150-199
High triglyceride level	200-499
Very high triglyceride level	>500
Source: National Cholesterol Education Program. Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. May 16 2001;285(19):2486-97.^[14]

Table 3. Classification of LDL Cholesterol and Non-HDL Cholesterol

Classification		LDL Goal, mg/dL	Non-HDL Goal, mg/dL
CHD and CHD risk equivalent, diabetes mellitus, and the following:	10-year risk for CHD >20%	< 100	< 130
Two or more risk factors and the following:	10-year risk < 20%	< 130	< 160
Two or more risk factors and the following:	0-1 risk factor	< 160	< 190
CHD = coronary heart disease; LDL = low-density lipoprotein; HDL = high-density lipoprotein. Source: National Cholesterol Education Program. Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. May 16 2001;285(19):2486-97.^[14]

Table 4. Fibric Acid Agents, Omega Acid Ethyl Esters, and Niacin Drug Characteristics ^[91]

Drug

Lipid Effects

Lipid Effects in Combination with Statin

Outcomes Data

Comments

Bezafibrate

LDL decrease: 9.6-25% (400 mg)

HDL increase: 15-24% (400 mg)

Triglyceride decrease: 25-43% (400 mg)

Further LDL decrease: 1.1% (400 mg)

Further HDL increase: 22% (400 mg)

Further triglyceride decrease: 31.7% (400 mg)

Secondary prevention: Prevents composite endpoint of MI and sudden death in a subgroup with triglycerides of 200 mg/dL or higher. No increase in non-CV death

First-line option for triglyceride >10 mmol/L

Option for triglyceride 5-10 mmol/L

Option for low HDL

Reversible increase in serum creatinine

Requires renal dose adjustment

Limited data with statins

Ezetimibe

LDL decrease: 18% (10 mg/day)

HDL increase: 1% (10 mg/day)

Triglyceride decrease: 8%

Further LDL decrease: 25%, as add-on

Further HDL increase: 3%, as add-on

Further triglyceride decrease: 14%, as add-on

Prevention of CV events in post-acute coronary syndrome patient when added to statin showed a benefit of reducing the primary endpoint (composite of CV death, MI, unstable angina requiring rehospitalization, coronary revascularization or stroke) by 6.4% vs statin alone

In intermediate outcomes studies, ezetimibe did not reduce regression of carotid intima-media thickness (surrogate marker) when added to a statin

Efficacy studied in combination with atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin

Role as statin add-on to reduce LDL if HDL and triglyceride satisfactory

Fenofibrate

LDL decrease: 20.6% (145 mg)

HDL increase: 11% (145 mg)

Triglyceride decrease: 23.5-50.6% (greatest drop in patients with highest triglycerides) (145 mg)

Further LDL decrease: 0-6% (200 mg)

Further HDL increase: 13-17% (200 mg)

Further triglyceride decrease: 20-32% (200 mg)

Prevention of CV events in type 2 diabetes: Did not reduce primary composite outcome (nonfatal MI or CV death). Improved outcomes included nonfatal MI (24% decrease), coronary revascularization (21% decrease), progression to albuminuria, and reduced laser treatments for retinopathy. Nonsignificant increase in risk of CV death.

First-line option for triglyceride >10 mmol/L (about 1000 mg/dL)

Option for triglyceride >500 mg/dL or 5-10 mmol/L

Option for low HDL

Requires renal dose adjustment

Associated with reversible increase in serum creatinine

Gemfibrozil

LDL: No effect

HDL increase: 6% (1200 mg/day)

Triglyceride decrease: 33-50% (greatest drop in patients with highest triglycerides) (1200 mg/day)

Further triglyceride decrease: 41%

Further HDL increase: 9%

Primary prevention of coronary heart disease

Secondary prevention of cardiac events in men with low HDL

First-line option for triglyceride >10 mmol/L (about 1000 mg/dL)

Option for triglyceride >500 mg/dL or 5-10 mmol/L

Option for low HDL

Requires renal dose adjustment

Avoid with statin

Icosapent ethyl

LDL decrease: 5%

HDL decrease: 4%

Triglyceride decrease: 27%

Further triglyceride decrease: 21.5% (4 g/day), 10.1% (2 g/day)

Further LDL decrease: 6.2% (4 g/day)

Secondary CV risk prevention; REDUCE-IT trial showed primary endpoint (major CV events) occurred in 24.7% of placebo compared with 18.2% of icosapent ethyl treated patients (p = 0.000001) ^[80]

Option for triglyceride >500 mg/dL

Safe for use with statins

Use caution with fish or shellfish allergy

Niacin

LDL decrease: 14-17% (Niaspan 2 g/day); 12% (niacin immediate-release 1.5 g/day and Niaspan 1.5 g/day)

HDL increase: 22-26% (2 g/day Niaspan); 17% (niacin immediate release 1.5 g/day); 20-22% (Niaspan 1.5 g/day)

Triglyceride decrease: 20-50%

Further LDL decrease: 1-5% (Niaspan 1 g/day); 10% (Niaspan 2 g/day)

Further HDL increase: 24% (Niaspan 2 g/day); 15-17% (Niaspan 1 g/day)

Further triglyceride decrease: 24% (Niaspan 2 g/day); 12-22% (Niaspan 1 g/day)

Secondary MI prevention; in combination with a resin, slows progression or promotes regression of atherosclerosis; reduces mortality

Option for triglyceride >500 mg/dL (about 5 mmol/L)

Raises HDL more than any other agent

Dose-dependent risk of hyperglycemia (especially in patients with type 2 diabetes) and liver toxicity

May increase risk of statin myopathy

Omega-3 ethyl esters

LDL increase: 44.5% (4 g/day)

HDL increase: 9.1% (4 g/day)

Triglyceride decrease: 45% (4 g/day)

LDL increase: 0.7% (4 g/day)

Further HDL increase: 3.4% (4 g/day)

Further triglyceride decrease: 29.5% (4 g/day)

Secondary prevention: Reduces cardiovascular death; sudden death; and combined endpoint of death, nonfatal MI, and nonfatal stroke

Secondary prevention in patients with, or at risk for, type 2 diabetes: did not reduce CV events

Option for triglyceride >500 mg/dL (about 5 mmol/L)

Safe for use with statins

Associated with an increase in risk for recurrence of symptomatic atrial fibrillation or flutter within first 3 months of therapy

Use with caution with fish or shellfish allergy

Table 5. Statin Drug Characteristics ^[92]

Drug	Potency (average LDL decrease)	Renal Considerations	Liver Function Monitoring
Atorvastatin	10 mg: 35-39% 20 mg: 43% 40 mg: 50% 80 mg: 55-60%	No dose adjustment necessary for reduced renal function	Check liver function tests at baseline and when clinically indicated
Fluvastatin	20 mg: 22% 40 mg: 25% 80 mg: 35% (as XL product)	In severe renal impairment, use daily doses >40 mg with caution	Check liver function tests at baseline and when clinically indicated
Lovastatin	10 mg: 21% 20 mg: 24-27% 40 mg: 30-31% 80 mg: 40-42% (as 40 mg BID)	If CrCl < 30 mL/min, use daily doses over 20 mg with caution	Check liver function tests at baseline and when clinically indicated
Pitavastatin	1 mg: 31-32% 2 mg: 36-39% 4 mg: 41-45%	For glomerular filtration rate 15-59 mL/min/1.73 m², including hemodialysis, initial daily dose is 1 mg, not to exceed 2 mg/day	Check liver function tests at baseline and when clinically indicated
Pravastatin	10 mg: 22% 20 mg: 32% 40 mg: 34% 80 mg: 37%	In significant renal impairment, start with 10 mg/day	Check liver function tests at baseline and when clinically indicated
Rosuvastatin	5 mg: 45% 10 mg: 46-52% 20 mg: 47-55% 40 mg: 55-63%	If CrCl < 30 mL/min/1.73 m² (but not on hemodialysis), starting dose is 5 mg/day, not exceed 10 mg/day Rosuvastatin levels in hemodialysis patients are about 50% higher than levels in normal renal function	Check liver function tests at baseline and when clinically indicated
Simvastatin	5 mg: 26% 10 mg: 30% 20 mg: 38% 40 mg: 29-41% 80 mg: 36-47%	In severe renal impairment, starting dose is 5 mg daily with close monitoring	Check liver function tests at baseline and when clinically indicated

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Author

Mary Ellen T Sweeney, MD Associate Professor of Medicine (Endocrinology, Diabetes, and Metabolism), Department of Medicine, Emory University School of Medicine; Physician, Division of Endocrinology, Veterans Administration Medical Center; Physician, Lipid Metabolism Clinic, Emory Healthcare, The Emory Clinic

Mary Ellen T Sweeney, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, National Lipid Association

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Hampton Roy, Sr, MD † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Acknowledgements

Steve Charles, MD Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Adjunct Professor of Ophthalmology, Columbia College of Physicians and Surgeons; Clinical Professor Ophthalmology, Chinese University of Hong Kong

Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society

Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Other; Topcon Medical Lasers Consulting fee Consulting

Karen E Friday, MD, FACP Clinical Core Director of Tulane Xavier National Center of Excellence, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Tulane University School of Medicine

Karen E Friday, MD, FACP is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Heart Association, American Society for Clinical Nutrition, and Endocrine Society

Disclosure: AstraZeneca own AstraZeneca stock None; Merck own Merck stock None; Schering Plough own Schering Plough stock None; Medco Health own Medco Health stock None

Robert A Gabbay, MD, PhD Associate Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, Laurence M Demers Career Development Professor, Penn State College of Medicine; Director, Diabetes Program, Penn State Milton S Hershey Medical Center; Executive Director, Penn State Institute for Diabetes and Obesity

Robert A Gabbay, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, and Endocrine Society

Disclosure: Novo Nordisk Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching

Steven R Gambert, MD Professor of Medicine, Johns Hopkins University School of Medicine; Director of Geriatric Medicine, University of Maryland Medical Center and R. Adams Cowley Shock Trauma Center

Steven R Gambert, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American Geriatrics Society, Association of Professors of Medicine, Endocrine Society, and Gerontological Society of America

Disclosure: Nothing to disclose.

Romesh Khardori, MD, PhD Professor and Director, Division of Endocrinology, Metabolism, and Molecular Medicine, Southern Illinois University School of Medicine

Romesh Khardori, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society of Andrology, Endocrine Society, and Illinois State Medical Society

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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