Hyperlipidemia

Latest updates: November 14, 2013

On November 12, 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) published four related guidelines on the prevention of atherosclerotic cardiovascular disease (ASCVD) events, with a focus on cholesterol, obesity, and lifestyle management tools.

The new guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults states that systematic evidence reviews indicated a consistent reduction in ASCVD events with statin therapy in secondary and primary prevention populations, with the exception of no reduction seen in ASCVD events in those patients with NYHA class II-IV heart failure or those receiving maintenance hemodialysis. The guideline further states, however, that those trials 'were not designed to evaluate the effect of titrated (dose-adjusted) statin treatment to achieve prespecified LDL–C or non–HDL-C goals.' In addition, the Expert Panel's review determined that use of therapy (eg, niacin) to additionally lower non–HDL-C, once an LDL-C target was achieved, did not further reduce ASCVD events.

The 2013 ACC/AHA guideline, therefore, recommends a fundamental change in patient management from the National Heart, Lung, and Blood Institute's (NHLBI) Adult Treatment Panel III (ATP3) recommendations, the acknowledged leading guideline since 2004. In contrast to the ATP3, the ACC/AHA recommends treating all patients who fall into one of the following four statin benefit groups with either standardized, fixed-dose, high-intensity (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) or moderate-intensity (atorvastatin 10–20 mg, rosuvastatin 5–10 mg, simvastatin 20–40 mg, or pravastatin 40–80 mg, among other statins) therapies:

1. Individuals with clinical ASCVD should receive high-intensity statin therapy (moderate-intensity for those patients >75 years)

2. Individuals with primary elevations of LDL–C ≥190 mg/dL should receive high-intensity statin therapy

3. Individuals 40 to 75 years of age with diabetes and LDL-C 70 to 189 mg/dL should receive at least moderate-intensity statin therapy

4. Individuals 40 to 75 years of age without clinical ASCVD or diabetes with LDL-C 70 to 189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher should receive moderate- or high-intensity statin therapy

Of related interest, the new AHA/ACC guideline on lifestyle management to reduce cardiovascular risk continues to recommend any medically recognized heart-healthy dietary program. For lowering LDL-C, the strongest recommendations continue to advise a reduction in the percentage of calories from saturated and trans fats, aiming for 5% to 6% of calories from saturated fat.

The 2013 ACC/AHA guideline on the assessment of cardiovascular risk introduces a new 10-year and lifetime cardiovascular risk assessment tool based on a pooled cohort to predict first ASVCD-related event in non-Hispanic men and women. Routine measurement of carotid intima-media thickness is not recommended as part of primary prevention.

Summary

Description

• Hyperlipidemia is a heterogeneous group of disorders characterized by an excess of lipids in the bloodstream. These lipids include cholesterol, cholesterol esters, phospholipids, and triglycerides. Lipids are transported in the blood as large 'lipoproteins'
• Lipoproteins are divided into five major classes, based on density: chylomicrons, very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Most triglyceride is transported in chylomicrons or VLDL, and most cholesterol is carried in LDL and HDL
• Primary hyperlipidemias are probably genetically based, but the genetic defects are known for only a minority of patients
• Secondary hyperlipidemia may result from diseases such as diabetes, thyroid disease, renal disorders, liver disorders, and Cushing's syndrome, as well as obesity, alcohol consumption, estrogen administration, and other drug-associated changes in lipid metabolism
• Hyperlipidemia is a major, modifiable risk factor for atherosclerosis and cardiovascular disease, including coronary heart disease; this is true both of disorders involving hypercholesterolemia and hypertriglyceridemia

Synonyms

• Hypercholesterolemia
• Hypertriglyceridemia
• Hyperlipoproteinemia
• Dyslipidemia
• High serum cholesterol

Immediate action

It has been shown that risk of recurrent cardiovascular events is significantly lowered with intensive statin therapy in patients at high risk. Intensive statin therapy should be considered as part of initial therapy in any patient admitted with an acute coronary syndrome or myocardial infarction.

Urgent action

Patients with documented, stable coronary artery disease and/or diabetes mellitus should have their lipid levels measured and be started on appropriate lipid management, including lifestyle modifications.

Key points

Hypercholesterolemia

• Hypercholesterolemia, regardless of cause, is a major modifiable risk factor for coronary artery disease
• Hyperlipidemia is usually asymptomatic until serum lipid levels are severely elevated, and well beyond the range at which cardiovascular morbidity and mortality are increased
• Identification of patients who would benefit from lipid-lowering therapy, therefore, depends on screening of adults and certain children for high serum lipid levels, as well as obtaining a careful history to detect risk factors that suggest the patient would benefit from lipid-lowering therapy, even if serum lipid levels are 'normal'
• Effective and well-tolerated therapy for lowering LDL cholesterol (LDL-C) is now available, and should receive widespread application
• Epidemiologic studies predict that for each 1% reduction in the level of LDL-C, there is a 1% to 1.5% reduction in the risk of major cardiovascular events
• Treatment goals for lipid-lowering therapy depend on risk stratification of the patient to identify appropriate lipid level 'targets'
• Lifestyle modifications, such as weight loss, exercise, and dietary changes, are also key in long-term management

Hypertriglyceridemia

• Drug therapy for elevated triglycerides is presently available, and new drugs are being developed
• Contrary to widespread belief, hypertriglyceridemia is also a modifiable risk factor for cardiovascular disease

Background

Cardinal features

• Hyperlipidemia is a group of disorders characterized by an excess of serum cholesterol, especially excess LDL-C and/or excess triglycerides
• Hypercholesterolemia is generally asymptomatic
• Hypertriglyceridemia is generally asymptomatic until triglyceride levels are sustained above 1000 mg/dL - symptoms then include dermatologic manifestations, such as eruptive xanthomas, and gastrointestinal manifestations, such as pancreatitis
• Hyperlipidemias are most often genetically determined, but can be caused or amplified by abnormal diet, drugs, and certain disease conditions
• Drugs associated with hyperlipidemias include immunosuppressive therapy, thiazide diuretics, progestins, retinoids, anabolic steroids, glucocorticoids, HIV protease inhibitors, alcohol, retinoic acid, and beta-blockers
• Diseases associated with secondary hyperlipidemias include diabetes mellitus (type I and type II), hypothyroidism, Cushing's syndrome, chronic kidney disease, nephrotic syndrome, and cholestatic disorders
• Hyperlipidemia is a major modifiable risk factor for atherosclerosis and cardiovascular disease, including coronary heart disease
• Treatment goals are based on absolute serum levels of lipids, and/or risk stratification of patients - more aggressive treatment to achieve lower lipid target levels is indicated in higher-risk patients
• Evidence shows that effective therapy to lower serum LDL-C is associated with dramatic benefits in terms of short-term morbidity and mortality in patients with coronary artery disease, and long-term morbidity and mortality even in low-risk patients

Causes

Common causes

• Familial combined hypercholesterolemia is the most common primary lipid disorder, characterized by moderate elevation of plasma triglycerides and cholesterol and reduced plasma HDL-C
• Familial hypertriglyceridemia

Rare causes

Hypercholesterolemia

• Familial hypercholesterolemia with raised cholesterol
• Familial dysbetalipoproteinemia (Type III hyperlipoproteinemia)
• Familial defective apolipoprotein (Apo) B₁₀₀
• Apo AI deficiency
• Autosomal recessive hypercholesterolemia
• Tangier disease
• Wolman disease
• Sitosterolemia
• Remnant hyperlipoproteinemia with marked combined hyperlipidemia
• Polygenic hypercholesterolemia
• Lecithin:cholesterol acyltransferase deficiency
• Cholesteryl ester transfer protein deficiency

Hypertriglyceridemia

• Lipoprotein lipase deficiency (familial chylomicronemia syndrome, type I hyperlipoproteinemia) with extremely raised triglycerides and moderately raised cholesterol
• Apo CII deficiency

Serious causes

Homozygous familial hypercholesterolemia.

Contributory or predisposing factors

Other diseases that may contribute to hyperlipidemia include:

• Insulin-dependent diabetes mellitus
• Non-insulin dependent diabetes mellitus
• Hypothyroidism
• Cushing's syndrome
• Renal failure and nephrotic syndrome
• Cholestatic disorders
• Dysproteinemias

Drugs associated with hyperlipidemia include:

• Anabolic steroids
• Retinoids
• Birth control pills and estrogens
• Corticosteroids
• Thiazide diuretics
• Protease inhibitors
• Beta-blockers

Dietary causes include:

• Fat intake per total calories greater than 40%
• Saturated fat intake per total calories greater than 10%
• Cholesterol intake greater than 300 mg per day
• Habitual excessive alcohol use

Lifestyle contributing factors include:

• Habitual excessive alcohol use
• Obesity
• Lack of exercise

Epidemiology

Incidence and prevalence

Prevalence

Hypercholesterolemia

• Fifty percent of the population has an increased plasma lipid level, resulting in increased risk of coronary heart disease
• Plasma cholesterol >292 mg/dL (>7.5 mmol/L): 2000/100,000
• Ethnic groups adopting a 'western' lifestyle tend to have higher levels of plasma lipids
• Familial combined hyperlipidemia: 500/100,000 (also associated with high triglycerides)
• Familial heterozygous hypercholesterolemia: 200/100,000
• Familial dysbetalipoproteinemia (type III hyperlipoproteinemia): 1% of the general population are genetically homozygous, but only a small minority develop disease (also associated with high triglycerides)
• Other familial hyperlipidemias: 250/100,000
• Homozygous familial hypercholesterolemia: 0.1/100,000
• Type I hyperlipoproteinemia: approximately 0.1/100,000 (also associated with high triglycerides)

Hypertriglyceridemia

• Fasting triglyceride level >200 mg/dL: 10% in men >30 years and women >55 years (in the U.S.)
• Severe hypertriglyceridemia (>2000 mg/dL); 18/100,000 in white populations; higher in diabetic patients or patients with alcoholism
• Familial hypertriglyceridemia: 200/100,000
• Lipoprotein lipase deficiency: 0.1/100,000 in the U.S.; the prevalence is much higher in Quebec, Canada
• Apoprotein CII deficiency: <0.1/100,000

Demographics

Age

• Total and LDL-C rise about 20% in men aged 20 to 50 years
• Total and LDL-C rise steadily about 30% in women aged 20 to 60 years
• Younger women have lower levels than men
• Homozygous familial hypercholesterolemia manifests itself from birth

Gender

Incidence is higher among men than women.

Race

• Total cholesterol and LDL-C levels are similar in whites and blacks
• Triglycerides are lower and HDL-C levels tend to be higher in the African-American population
• Ethnicity determines absolute risk of coronary disease for given levels of cholesterol
• Asian-Indians have the highest risk
• Chinese have the lowest risk
• Europeans have an intermediate risk

Genetics

• Familial combined hyperlipidemia: 500/100,000; inheritance is autosomal dominant and likely to involve one of multiple genetic defects
• Familial hypercholesterolemia (deficit of LDL receptors) and familial defective Apo B₁₀₀: heterozygotes (200/100,000 people) and homozygotes (0.1/100,000) with gene inherited as an autosomal dominant defect
• Familial hypertriglyceridemia: 200/100,000, most likely inherited as an autosomal dominant defect
• Lipoprotein lipase deficiency and hepatic lipase deficiency: very rare autosomal recessive conditions
• Hypercholesterolemia in the majority of the general public is attributed to high-fat diets and poorly understood susceptibility and modifier genes

Geography

• Mean plasma lipids levels vary between different populations around the world and within different ethnic groups in North America
• Differences in plasma lipid levels can be partly explained by dietary and lifestyle differences

Socioeconomic status

• Awareness of dietary factors that affect plasma lipid levels increases with higher educational levels
• Low-cost food items are often higher in saturated fats and lower in nutritional value

Codes

ICD-9 code

• 272 Disorders of lipoid metabolism
• 272.0 Pure hypercholesterolemia
• 272.1 Pure hyperglyceridemia
• 272.2 Mixed hyperlipidemia
• 272.3 Hyperchylomicronemia
• 272.4 Other and unspecified hyperlipidemia