Hyperlipidemia

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
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