DRG Category: 642
Mean LOS: 4.1 days
Description: Medical: Inborn and Other Disorders of Metabolism
Hyperlipoproteinemia is a condition of increased lipoprotein particles (fats) in the blood caused by an increased rate of synthesis or a decreased rate of lipoprotein breakdown. Because lipoproteins transport triglycerides and cholesterol in the plasma, an increased level may cause complications such as pancreatitis and atherosclerosis leading to coronary heart disease, myocardial infarction, stroke, and sudden death.
Lipids are a mixed group of biochemical substances manufactured by the body or derived from metabolism of ingested substances. The plasma lipids (cholesterols, triglycerides, phospholipids, and free fatty acids) are derived from dietary sources and lipid synthesis. Cholesterol and triglycerides are implicated in atherogenesis. Hyperlipemia, also known as hyperlipidemia, occurs with elevated plasma cholesterol or triglyceride levels or both and is present in all hyperlipoproteinemias.
Hyperlipidemia, an elevation of serum cholesterol or triglycerides, can be primary or secondary to another underlying condition. Lipoprotein elevation, or hyperlipoproteinemia, is described by five specific types: types I, II, III, IV, and V (Table 1).
Table 1 Types of Hyperlipoproteinemia
| TYPE | DEFINITION AND CAUSE | ASSESSMENT | LIPID LEVEL |
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| I | Fat-induced hyperlipidemia or idiopathic familial hyperlipidemia, which is a rare condition caused by deficient or abnormal lipase; rare genetic disorder that is present in infancy | Recurrent attacks of severe abdominal pain after fat intake; malaise; anorexia; may be associated with pancreatitis | Triglycerides 1,000–10,000+ mg/dL, normal cholesterol | | II | Familial hyperbetalipoproteinemia and essential familial hypercholesterolemia (FH) because of deficient cell surface receptors | Chest pain from prematurely accelerated coronary artery disease; tendinous xanthomas (firm masses) on Achilles tendons, tendons of hands and feet; juvenile corneal arcus (grayish ring around the cornea of the eye) | Elevated cholesterol and triglycerides, elevated low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL) | | III | Familial broad-beta disease xanthoma tuberosum caused by a deficient LDL receptor | Chest pain from early progression of atherosclerosis; xanthomas over elbows, knees, palms, and fingertips | Elevated cholesterol and triglycerides; elevated intermediate-density lipoproteins | | IV | Endogenous hypertriglyceridemia and hyperbetalipoproteinemia with an idiopathic cause; often associated with obesity and diabetes | Chest pain from early progression of coronary heart disease (CHD); obesity, hypertension | Triglycerides < 1,000 mg/dL, normal cholesterol, elevated VLDL | | V | Mixed hypertriglyceridemia from defective triglyceride clearance; often secondary to other disorders such as renal disease or obesity | Abdominal pain from pancreatitis; visual changes; xanthomas on arms and legs; enlarged liver and spleen | Triglycerides > 1,000 mg/dL, elevated cholesterol, normal LDL |
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Primary hyperlipoproteinemia results from rare genetic disorders. Secondary hyperlipoproteinemia occurs as a manifestation of other diseases, which include hypothyroidism, nephrotic syndrome, diabetes mellitus, alcoholism, glycogen storage disease (type I), Cushing syndrome, acromegaly, anorexia, renal disease, liver diseases, immunological disorders, stress, and the use of oral contraceptives or glucocorticoids.
Familial hypercholesterolemia (FH) is an autosomal disorder caused by mutations in the LDL receptor gene (LDLR), leading to increases in both total cholesterol and low-density lipoprotein levels. FH is associated with an increased risk of coronary artery disease. Mutations in the lipoprotein lipase (LPL) gene cause autosomal recessive hyperlipoproteinemia, whereas APOE mutations yield a dominant disorder with incomplete penetrance. A clinically identical phenotype is produced by mutations in the apolipoprotein B-100 gene (APOB). Other genetic and environmental factors may contribute.
Type I disease is a rare disorder that is present at birth. Type II disease usually causes symptoms in young adults in their 20s, but symptoms may begin as early as age 10 years. Symptoms from type III disease usually occur during the teenage years or early 20s. Type IV disease, more common than the other forms of hyperlipoproteinemia, occurs primarily in middle-aged men. Type V disease occurs in late adolescence or in the early 20s.
While there are no differences in incidence and prevalence in males and females, women with familial hypercholesterolemia are underrepresented in research and have to interrupt therapy during childbearing. Women also are less likely to be on guideline-recommended statin medications and less likely to be on nonstatin agents such as PCSK9 inhibitors as compared to men. As a result, women are less likely than men to achieve target low-density lipoprotein cholesterol (LDL-C) goals (Balla et al., 2020). While the condition is found in children, adolescents, and young adults, type IV is seen most often in middle-aged and older adults.
In general, Black persons are more likely to have hyperlipoproteinemia than White persons. People of Asian and Indian-Asian descent have lower prevalence than other groups in developed countries. Sexual and gender minority status has no known effect on the risk for hyperlipoproteinemia.
Hyperlipoproteinemia has a high prevalence in developed countries. Little is known about the prevalence in developing countries, but if trends in hyperlipoproteinemia follow obesity trends, prevalence will increase as developing regions become more urbanized.
PLANNING AND IMPLEMENTATION
Collaborative
The primary treatment is dietary management, weight reduction, increased physical activity, and the restriction of saturated animal fat and cholesterol intake. Adding polyunsaturated vegetable oils to the diet helps reduce LDL-C concentration. Secondary treatment is aimed at reducing or eliminating aggravating factors, such as alcoholism, diabetes mellitus, or hypothyroidism. To reduce risk factors that contribute to atherosclerosis, the regimen includes treating hypertension, implementing an exercise program, controlling blood sugar, and stopping tobacco use. For type V hyperlipoproteinemia, female patients are taken off oral contraceptives. Medications may also be prescribed to lower the plasma concentration of lipoproteins, either by decreasing their production or by increasing their removal from plasma.
Target levels for lipoprotein are shown in Table 2.
Table 2 Target Levels for Lipoprotein
| LEVEL OF RISK | DEFINITION | TARGET LIPOPROTEIN LEVEL RISK |
|---|
| Low risk | All must be present: Nonsmoker; total cholesterol < 200 mg/dL, HDL-C > 40 mg/dL; systolic blood pressure (BP) < 120, diastolic BP < 80; no evidence of diabetes; not overweight; no family history of premature vascular disease | LDL-C should be lowered to < 160 mg/dL | | Moderate risk | Does not fit in low-risk or high-risk categories | LDL-C should be lowered to < 130 mg/dL; consideration to lower LDL-C to < 100 mg/dL | | High risk | Any of the following present: Known coronary artery disease or other vascular disease; type 2 diabetes; over age 65 years with multiple (more than one) risk factors | LDL-C should be lowered to < 100 mg/dL; consideration to lowering LDL-C to < 70 mg/dL |
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In rare instances, for patients who cannot tolerate medication therapy, surgical creation of an ileal bypass may be necessary to accelerate the loss of bile acids in the stool and lower plasma cholesterol levels. For children with severe disease, surgery to create a portacaval shunt may be performed as a last resort to decrease plasma cholesterol levels. Plasma exchanges may also be used to reduce cholesterol levels.
| Medication or Drug Class | Dosage | Description | Rationale |
|---|
| Drugs that lower LDL-C | Varies with drug | Statins such as lovastatin, pravastatin, simvastatin, fluvastatin, and atorvastatin are the first line of therapy; bile acid sequestrant resins (cholestyramine, colestipol); nicotinic acid (niacin); 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors; estrogen in postmenopausal women | Lower the plasma concentration of lipoproteins either by decreasing their production or by increasing their removal from plasma |
| Drugs that increase HDL-C | Varies with drug | Nicotinic acid (niacin), estrogen in postmenopausal women | Lower the plasma concentration of lipoproteins either by decreasing their production or by increasing their removal from plasma |
Independent
Teach the patient about ways to manage diet to control the disorder. Urge the patient to adhere to a 1,000- to 1,500-calorie daily diet and avoid excess sugar intake. Explain the components of the lipid profile and their ramifications and discuss various means of lowering VLDL and LDL levels and increasing HDL levels. Several dietary additions are thought to reduce LDL cholesterol, such as 1.5 cups of oatmeal with fiber-containing fruit (soluble fiber reduces LDL), 1.5 ounces of nuts (walnuts, almonds, peanuts, pecans), olive oil, and fatty fish containing omega-3 fatty acids such as mackerel, lake trout, herring, sardines, albacore tuna, and salmon.
Explain the prescribed medication regimen and provide verbal and written information to the patient or significant others. Refer to effective programs or support groups for controlling cigarette and alcohol use. Teach alternative methods of contraception to the female patient who can no longer use oral contraceptives. Encourage strategies for weight loss and weight maintenance.
A patient faces significant health threats unless the patient makes permanent lifestyle changes. Encourage the patient to verbalize fears, such as those concerning CHD. Offer support and provide clear explanations for the patient's questions about the lifestyle changes and consequences.
Evidence-Based Practice and Health Policy
Sergei, N., Pokrovsky, S., Afanasieva, O., & Ezhov, M. (2020). Therapeutic apheresis for management of Lp(a) hyperlipoproteinemia. Current Atherosclerosis, 22, 1–11.
- High lipoprotein(a) (Lp[a]) level is an independent cardiovascular risk factor with higher prevalence among patients with atherosclerotic cardiovascular disease (ASCVD). Lipoprotein apheresis (LA) is an effective method for elimination of lipoproteins, but it is approved only in some countries for treatment of elevated Lp(a) in people with progressive ASCVD.
- The purpose of this review was to present the information on optimal management of Lp(a) hyperlipoproteinemia by LA. Most clinical studies suggest inflammatory and prothrombotic processes begin to reduce in a few months, and there is plaque regression in 1.5 years. Treatment with LA for 2 to 5 years shows ongoing reduction by 60% to 80%. Therapeutic Lp(a) apheresis is the only method that solely targets Lp(a).