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Description : Lipoproteins are complexes of lipids and proteins that are essential for transport of cholesterol, triglycerides (TGs), and fat-soluble vitamins in the blood.

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Disorders of Lipoprotein Metabolism Mary Erika Maxine A. Talens 2nd year
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Lipoproteins are complexes of lipids and proteins that are essential for transport of cholesterol, triglycerides (TGs), and fat-soluble vitamins in the blood.
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LIPOPROTEIN CLASSIFICATIONAND COMPOSITION Lipoproteins large macromolecular complexes composed of lipids and proteins that transport poorly soluble lipids (primarily TGs, cholesterol, and fat-soluble vitamins) through body fluids (plasma, interstitial fluid, and lymph) to and from tissues play an essential role in the absorption of dietary cholesterol, long-chain fatty acids, and fat-soluble vitamins; the transport of TGs, cholesterol, and fat-soluble vitamins from the liver to peripheral tissues the transport of cholesterol from peripheral tissues to the liver and intestine
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The plasma lipoproteins are divided into five major classes based on their relative density: Chylomicrons Very-low-density lipoproteins (VLDLs) Intermediate-density lipoproteins (IDLs) Low-density lipoproteins (LDLs) High-density lipoproteins (HDLs)
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Chylomicrons are the most lipid-rich and therefore least dense lipoprotein particles, whereas HDLs have the least lipid and are there- fore the most dense lipoproteins.
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Apolipoproteins are required for the assembly, structure, function, and metabolism of lipoproteins provide a structural basis for lipoproteins activate enzymes important in lipoprotein metabolism act as ligands for cell surface receptors
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One critical role of lipoproteins is the efficient transport of dietary lipids from the intestine to tissues that require fatty acids for energy or store and metabolize lipids and of intestinal cholesterol to the liver. Dietary lipids are hydrolyzed by lipases within the intestinal lumen and emulsified with bile acids to form micelles. Dietary cholesterol, fatty acids, and fat-soluble vitamins are absorbed in the proximal small intestine. Longer-chain fatty acids (>12 carbons) are incorporated into TGs and packaged with apoB-48 in a process that requires the action of the microsomal TGs transfer protein (MTP), to form chylomicrons. TRANSPORT OF INTESTINALLY DERIVED DIETARY LIPIDS BY CHYLOMICRONS
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Nascent chylomicrons are secreted into the intestinal lymph and delivered via the thoracic duct directly to the systemic circulation, where they are extensively processed by peripheral tissues before reaching the liver. The particles encounter lipoprotein lipase (LPL), which is anchored to a glycosylphosphatidylinositol-anchored protein, GPIHBP1, that is attached to the endothelial surfaces of capillaries in adipose tissue, heart, and skeletal muscle The released free fatty acids are taken up by adjacent myocytes or adipocytes and either oxidized to generate energy or reesterified and stored as TG. TRANSPORT OF INTESTINALLY DERIVED DIETARY LIPIDS BY CHYLOMICRONS
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Another key role of lipoproteins is the transport of hepatic lipids from the liver to the periphery to provide an energy source during fasting. During the fasting state, lipolysis of adipose TGs generates fatty acids that are transported to the liver, and the liver is also capable of synthesizing fatty acids through de novo lipogenesis. After secretion by the liver into the plasma, as with chylomicrons, the TGs of VLDL are hydrolyzed by LPL, especially in muscle, heart, and adipose tissue. After the relatively TG-depleted VLDL remnants dissociate from LPL, they are referred to as IDLs The liver removes ~40–60% of IDL by receptor–mediated endocyto- sis via binding to apoE, which is acquired through transfer of this protein from HDL. The remainder of IDL is further remodeled by hepatic lipase (HL) to form LDL. TRANSPORT OF OF HEPATICALLY DERIVED LIPIDS BY VLDL AND LD
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DISORDERS OF ELEVATED CHOLESTEROL AND TGS Disorders of lipoprotein metabolism are collectively referred to as “dyslipidemias.” Dyslipidemias are generally characterized clinically by increased plasma levels of cholesterol, TGs, or both The majority of patients with dyslipidemia have some combination of genetic predisposition (often polygenic) and environmental contribution (diet, lifestyle, medical condition, or drug). Patients with markedly elevated levels of TGs may be at risk for acute pancreatitis and require intervention to reduce this risk.
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DYSLIPIDEMIA CAUSED BY EXCESSIVE HEPATIC SECRETION OF VLDL Excessive production of VLDL by the liver is one of the most common causes of dyslipidemia. Individuals with excessive hepatic VLDL production usually have elevated fasting TGs and low levels of HDL cholesterol (HDL-C). A cluster of other metabolic risk factors are often found in association with VLDL overproduction, including obesity, glucose intolerance, insulin resistance, and hypertension Some of the major factors that drive hepatic VLDL secretion include a high-carbohydrate diet, excessive alcohol use, obesity and insulin resistance, nephrotic syndrome, and genetic factors.
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DYSLIPIDEMIA CAUSED BY EXCESSIVE HEPATIC SECRETION OF VLDL Secondary Causes of VLDL Overproduction HIGH CARBOHYDRATE DIET - Some of the newly synthesized fatty acids are esterified, forming TGs, and secreted in VLDL. Thus, excessive intake of calories as carbohydrates. ALCOHOL - Excessive alcohol consumption inhibits hepatic oxidation of free fatty acids, thus promoting hepatic TG synthesis and VLDL secretion. OBESITY AND INSULIN RESISTANCE - More free fatty acids are delivered from the expanded and insulin-resistant adipose tissue to the liver, where they are re- esterified in hepatocytes to form TGs, which are packaged into VLDLs for secretion into the circulation. In addition, the increased insulin levels promote increased fatty acid synthesis in the liver. NEPHROTIC SYNDROME - attributed to the effects of hypoalbuminemia leading to increased hepatic protein synthesis. CUSHING’S SYNDROME - Endogenous or exogenous glucocorticoid excess is associated with increased VLDL synthesis and secretion and hypertriglyceridemia.
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DYSLIPIDEMIA CAUSED BY EXCESSIVE HEPATIC SECRETION OF VLDL Primary (Genetic) Causes of VLDL Overproduction The best recognized inherited condition associated with VLDL overproduction is familial combined hyperlipidemia. FAMILIAL COMBINED HYPERLIPIDEMIA (FCHL) FCHL is generally char- acterized by elevations in plasma levels of TGs (VLDL) and LDL-C (including small dense LDL) and reduced plasma levels of HDL-C. FCHL can manifest in childhood but is usually not fully expressed until adulthood. The disease clusters in families, and affected family members typically have one of three possible phenotypes: (1) elevated plasma levels of LDL-C, (2) elevated plasma levels of TGs due to elevation in VLDL, or (3) elevated plasma levels of both LDL-C and TG.
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DYSLIPIDEMIA CAUSED BY EXCESSIVE HEPATIC SECRETION OF VLDL Primary (Genetic) Causes of VLDL Overproduction The best recognized inherited condition associated with VLDL overproduction is familial combined hyperlipidemia. FAMILIAL COMBINED HYPERLIPIDEMIA (FCHL) Patients with FCHL have substantially elevated plasma levels of apoB, often disproportionately high relative to the plasma LDL-C concentration, indicating the presence of small dense LDL particles, which are characteristic of this syndrome. 2. Lipodystrophy - is a condition in which the generation of adipose tissue generally or in certain fat depots is impaired. Lipo- dystrophies are often associated with insulin resistance and elevated plasma levels of VLDL and chylomicrons due to increased fatty acid synthesis and VLDL production, as well as reduced clearance of TG-rich particles.
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DYSLIPIDEMIA CAUSED BY IMPAIRED LIPOLYSIS OF TG-RICH LIPOPROTEINS Secondary Causes of Impaired Lipolysis of TRLs OBESITY AND INSULIN RESISTANCE -obesity, insulin resistance, and type 2 diabetes have been reported to be associated with variably reduced LPL activity. This may be due in 2893 part to the effects of tissue insulin resistance leading to reduced tran- scription of LPL in skeletal muscle and adipose Primary (Genetic) Causes and Genetic Predisposition to Impaired Lipolysis of TRLs FAMILIAL CHYLOMICRONEMIA SYNDROME - LPL is required for the hydrolysis of TGs in chylomicrons and VLDLs. While chylomicronemia predominates, elevated plasma levels of VLDL as well. Genetic deficiency or inactivity of LPL results in impaired lipolysis and profound elevations in plasma chylomicrons, causing familial chylomicronemia syndrome. The most common cause of FCS involves mutations in the LPL gene.
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DYSLIPIDEMIA CAUSED BY IMPAIRED LIPOLYSIS OF TG-RICH LIPOPROTEINS FAMILIAL HYPERTRIGLYCERIDEMIA (FHTG) FHTG is characterized by elevated fasting TGs without a clear secondary cause, average to below average LDL-C levels, low HDL-C levels, and a family history of hypertriglyceridemia. Plasma LDL-C levels are often reduced due to defective conversion of TG-rich lipoproteins to LDL. In contrast to FCHL, apoB levels are not elevated. The identification of other first- degree relatives with hypertriglyceridemia is useful in making the diagnosis.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Impaired uptake of LDL and remnant lipoproteins by the liver is another common cause of dyslipidemia. Downregulation of LDL receptor activity or genetic variation that reduces the activity of the LDL receptor pathway leads to elevations in LDL-C. One major factor that reduces LDL receptor activity is a diet high in saturated and trans fats. Other medical conditions that reduce LDL receptor activity include hypothyroidism and estrogen deficiency.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Secondary Causes of Impaired Hepatic Uptake of Lipoproteins HYPOTHYROIDISM Hypothyroidism - is associated with elevated plasma LDL-C levels due primarily to a reduction in hepatic LDL receptor function and delayed clearance of LDL. Thyroid hormone increases hepatic expression of the LDL receptor. All patients presenting with elevated plasma levels of LDL-C, especially if there has been an unexplained increase in LDL-C, should be screened for hypothyroidism. CHRONIC KIDNEY DISEASE Chronic kidney disease (CKD) is often associated with mild hypertriglyceridemia (150–400 mg/dL) due to the accumulation of VLDLs and remnant lipoproteins in the circulation.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Primary (Genetic) Causes of Impaired Hepatic Uptake of Lipoproteins FAMILIAL HYPERCHOLESTEROLEMIA (FH) - is an autosomal co-dominant disorder Characterized by elevated plasma levels of LDL-C In the absence of hypertriglyceridemia. FH is caused by mutations that lead to reduced function of the LDL receptor with the most common being mutations in the LDLR gene The reduction in LDL receptor activity in the liver results in a reduced rate of clearance of LDL from the circulation.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Primary (Genetic) Causes of Impaired Hepatic Uptake of Lipoproteins FAMILIAL HYPERCHOLESTEROLEMIA (FH) The diagnosis of FH is generally a clinical diagnosis based on hypercholesterolemia with LDL-C >190 mg/dL in the absence of a secondary etiology, and a family history of hypercholesterolemia and/or premature coronary disease. Secondary causes of significant hypercholesterolemia such as hypothyroidism, nephrotic syndrome, and obstructive liver disease should be excluded, but heterozygous FH patients require pharmacologic therapy for effective control of their LDL-C levels. FH patients should always be actively treated to lower plasma levels of LDL-C, preferably starting in childhood. Initiation of a diet low in saturated and trans fats is recommended. Statins are the initial drug class of choice, and usually a more potent member of the class.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Primary (Genetic) Causes of Impaired Hepatic Uptake of Lipoproteins FAMILIAL HYPERCHOLESTEROLEMIA (FH) Many heterozygous FH patients cannot achieve adequate control of their LDL-C levels even with high-intensity statin therapy, and a cholesterol absorption inhibitor (ezetimibe), a PCSK9 2895 inhibitor, or a bile acid sequestrant are the next-line classes of drugs.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Primary (Genetic) Causes of Impaired Hepatic Uptake of Lipoproteins AUTOSOMAL RECESSIVE HYPERCHOLESTEROLEMIA (ARH) - ARH is a very rare autosomal recessive disorder that was originally reported in individuals of Sardinian descent. The disease is caused by mutations in the gene LDLRAP1 encoding the protein LDLR adaptor protein (also called the ARH protein) which is required for LDL receptor–mediated endocytosis in the liver. Sitosterolemia - is a rare autosomal recessive disease that is caused by biallelic loss-of-function mutations in either of two members of the ATP-binding cassette (ABC) half transporter family, ABCG5 and ABCG8. These genes are expressed in both enterocytes and hepatocytes.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Primary (Genetic) Causes of Impaired Hepatic Uptake of Lipoproteins LYSOSOMAL ACID LIPASE DEFICIENCY (LALD) LALD, also known as cholesteryl ester storage disease is an autosomal recessive disorder caused by loss-of-function variants in both alleles of the gene LIPA encoding the enzyme lysosomal acid lipase (LAL). Genetic deficiency of LAL results in accumulation of neutral lipid in the hepatocytes, leading to hepatosplenomegaly, microvesicular steatosis, and ultimately fibrosis and end-stage liver disease. LALD should be suspected in nonobese patients with elevated LDL-C, low HDL-C, and evidence of fatty liver in the absence of overt insulin resistance.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Primary (Genetic) Causes of Impaired Hepatic Uptake of Lipoproteins FAMILIAL DYSBETALIPOPROTEINEMIA (FDBL) FDBL (also known as type III hyperlipoproteinemia) is usually a recessive disorder characterized by a mixed hyperlipidemia (elevated cholesterol and TGs) due to the accumulation of remnant lipoprotein particles FDBL is due to genetic variants of apoE, most commonly apoE2, that result in an apoE protein with reduced ability to bind lipoprotein receptors. The most common precipitating factors are a high-fat diet, diabetes mellitus, obesity, hypothyroidism, renal disease, HIV infection, estrogen deficiency, alcohol use, or certain drugs. Patients with FDBL usually present in adulthood with hyperlipidemia, xanthomas, or premature coronary or peripheral vascular disease.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Primary (Genetic) Causes of Impaired Hepatic Uptake of Lipoproteins FAMILIAL DYSBETALIPOPROTEINEMIA (FDBL) FDBL Two distinctive types of xanthomas, tuberoeruptive and palmar, are seen in FDBL patients. Tuberoeruptive xanthomas begin as clusters of small papules on the elbows, knees, or buttocks and can grow to the size of small grapes. Palmar xanthomas (alternatively called xanthomata striata palmaris) are orange-yellow discolorations of the creases in the palms and wrists. Both of these xanthoma types are virtually pathognomonic for FDBL.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Primary (Genetic) Causes of Impaired Hepatic Uptake of Lipoproteins FAMILIAL DYSBETALIPOPROTEINEMIA Because FDBL is associated with increased risk of premature ASCVD, it should be treated aggressively. Patients with FDBL are typically diet-responsive and can respond favorably to weight reduction and to low-cholesterol, low-fat diets. Alcohol intake should be curtailed. Pharmacologic therapy is often required, and statins are the first line in management.
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DYSLIPIDEMIA CAUSED BY IMPAIRED HEPATIC UPTAKE OF APOB-CONTAINING LIPOPROTEINS Primary (Genetic) Causes of Impaired Hepatic Uptake of Lipoproteins HEPATIC LIPASE DEFICIENCY HL deficiency is a very rare autosomal recessive disorder characterized by elevated plasma levels of cholesterol and TGs (mixed hyperlipidemia) due to the accumulation of lipoprotein remnants, accompanied by elevated plasma level of HDL-C. The diag- nosis is confirmed by measuring HL activity in postheparin plasma and/or confirmation of loss-of-function mutations in both alleles of HL/LIPC.
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Secondary causes of Dyslipidemia LIVER DISORDERS Because the liver is the principal site of formation and clearance of lipoproteins, liver disorders can affect plasma lipid levels in variety of ways. Hepatitis due to infection, drugs, or alcohol is often associated with increased VLDL synthesis and mild to moderate hypertriglyceridemia. Cholestasis is often associated with hypercholesterolemia. DRUGS Estrogen administration is associated with increased VLDL and HDL synthesis Plasma TG levels should be monitored when birth control pills or postmenopausal estrogen therapy is initiated to ensure that the increase in VLDL production does not lead to severe hypertriglyceridemia.
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INHERITED CAUSES OF LOW LEVELS OF APoB-CONTAINING LIPOPROTEINS Abetalipoproteinemia Abetalipoproteinemia is a rare autosomal recessive disease caused by loss-of-function mutations in the gene encoding microsomal TG transfer protein (MTP; gene name MTTP) Plasma levels of cholesterol and TG are extremely low in this disorder, and chylomicrons, VLDLs, LDLs, and apoB are undetectable in plasma. Abetalipoproteinemia usually presents in early childhood with diarrhea and failure to thrive due to fat malabsorption. The initial neurologic manifestations are loss of deep tendon reflexes, followed by decreased distal lower extremity vibratory and proprioceptive sense, dysmetria, ataxia, and the development of a spastic gait, often by the third or fourth decade. Most of the clinical manifestations of abetalipoproteinemia result from defects in the absorption and transport of fat-soluble vitamins.
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Familial Hypobetalipoproteinemia (FHBL) FHBL generally refers to a condition of low total cholesterol, LDL-C, and apoB due to mutations in the APOB gene. Most of the mutations causing FHBL result in a truncated apoB protein, resulting in impaired assembly and secretion of chylomicrons from enterocytes and VLDL from the liver.
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Familial Combined Hypolipidemia Nonsense mutations in both alleles of the gene Angiopoietin-like 3 (ANGPTL3) lead to low plasma levels of all three major lipid fractions—TG, LDL-C, and HDL-C
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PCSK9 Deficiency Another inherited cause of low LDL-C results from loss-of-function mutations in PCSK9. PCSK9 is a secreted protein that binds to the extracellular domain of the LDL receptor in the liver and promotes the degradation of the receptor.
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INHERITED CAUSES OF VERY LOW LEVELS OF HDL-C Gene Deletions in the APOA5-A1-C3-A4 Locus and Coding Mutations in APOA1 Complete genetic deficiency of apoA-I due to a complete deletion of the APOA1 gene results in the virtual absence of circulating HDL and appears to increase the risk of premature ASCVD.
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Tangier Disease (ABCA1 Deficiency) Tangier disease is a rare autosomal co-dominant form of extremely low plasma HDL-C levels that is caused by mutations in the gene encoding ABCA1
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Familial LCAT Deficiency the proportion of free cholesterol in circulating lipoproteins is greatly increased (from ~25% to >70% of total plasma cholesterol). Deficiency in this enzyme interferes with the maturation of HDL particles and results in rapid catabolism of circulating apoA-I.
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Primary Hypoalphalipoproteinemia The condition of low plasma levels of HDL-C (the “alpha lipoprotein”) is referred to as hypo- alphalipoproteinemia. defined as a plasma HDL-C level below the tenth percentile in the setting of relatively normal cholesterol and TG levels, no apparent secondary causes of low plasma HDL-C, and no clinical signs of LCAT deficiency or Tangier disease. This syndrome is often referred to as isolated low HDL.
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SCREENING Hypercholesterolemia is a cause of premature CHD that is highly treatable and therefore persons should be actively screened. Plasma lipid levels should be measured, preferably after a 12-h overnight fast, in all adults; guidelines suggest that screening of children between 9 and 11 years of age is also recommended.
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SCREENING Formula: LDL-C = total cholesterol – (TG/5) – HDL-C This formula is reasonably accurate if test results are obtained on fasting plasma and if the TG level does not exceed ~200 mg/dL; by convention it cannot be used if the TG level is >400 mg/dL.
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DIAGNOSIS A critical first step in managing a lipoprotein disorder is to attempt to determine the class or classes of lipoproteins that are increased or decreased in the patient. Once the dyslipidemia is accurately classified, efforts should be directed to rule out any possible secondary causes
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DIAGNOSIS A fasting glucose should be obtained in the initial workup of all subjects with an elevated TG level. Nephrotic syndrome and chronic renal insufficiency should be excluded by obtaining urine protein and serum creatinine.
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DIAGNOSIS Liver function tests should be performed to rule out hepatitis and cholestasis. Hypothyroidism should be ruled out by measuring serum thyroid-stimulating hormone.
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DIAGNOSIS Once secondary causes have been ruled out, attempts should be made to diagnose a primary lipid disorder.
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Severe Hypertriglyceridemia If the fasting plasma TG level is >750 mg/dL, the patient may have chylomicronemia. If the elevated TG levels are persistent and the total cholesterol-to-TG ratio is >8, particularly in the setting of a history of pancreatitis, familial chylomicronemia syndrome should be considered.
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Severe Hypercholesterolemia If the levels of LDL-C are very high (greater than a ninety-fifth percentile for age and sex) in absence of secondary causes, familial hypercholesterolemia should be considered, particularly if there is a family history of hypercholesterolemia and/or premature CHD.
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The major goals in the clinical management of lipoprotein disorders are: prevention of acute pancreatitis in patients with severe hypertriglyceridemia; and prevention of CVD and related cardiovascular events.
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MANAGEMENT OF SEVERE HYPERTRIGLYCERIDEMIA TO PREVENT PANCREATITIS It is generally considered appropriate medical practice to intervene in patients with TGs >500 mg/ dL in order to reduce the risk of pancreatitis. Lifestyle modification Descreased Alcohol intake Dietary fat intake should be restricted Weight loss
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Pharmacologic Therapy for Severe Hypertriglyceridemia Patients who persist in having fasting TG >500 mg/dL despite active lifestyle management are candidates for pharmacologic therapy. the two major classes of drugs used for management of these patients are fibrates and omega-3 fatty acids (fish oils).
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MANAGEMENT OF CHOLESTEROL TO PREVENT CARDIOVASCULAR DISEASE In contrast to hypertriglyceridemia and pancreatitis, there are abundant and compelling data that intervention to reduce LDL-C substantially reduces the risk of CVD, including myocardial infarction and stroke, as well as total mortality.
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MANAGEMENT OF CHOLESTEROL TO PREVENT CARDIOVASCULAR DISEASE The first approach to a patient with hypercholesterolemia and high cardiovascular risk is to make any necessary lifestyle changes. Weight loss Reduce saturated fats, trans fats, and cholesterol in the diet
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MANAGEMENT OF CHOLESTEROL TO PREVENT CARDIOVASCULAR DISEASE Pharmacologic Therapy for Hypercholesterolemia The decision to use LDL-lowering drug therapy statin being first-line therapy depends on the level of LDL-C as well as the level of cardiovascular risk
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Quiz time!
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1. Familial Hypertryglyceridemia is characterized by except: A. Low fasting TGs without a clear secondary cause B. Average to below average LDL-C levels, C. Low HDL-C levels D. Family history of hypertriglyceridemia
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2. Familial Hypercholesterolemia is characterized by except: A. Characterized by elevated plasma levels of HDL B. In the absence of hypertriglyceridemia. C. FH is caused by mutations that lead to reduced function of the LDL receptor D. Most common being mutations in the LDLR gene
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3. This is virtually pathognomonic for Familial Dysbetalipoproteinemia (FDBL)? Tuberoeruptive Xanthomas Palmar xanthomas Both A and B None of the Above
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4. Nonsense mutations in both alleles of the gene Angiopoietin-like 3 (ANGPTL3) lead to low plasma levels of all three major lipid fractions—TG, LDL-C, and HDL-C A. Abetalipoproteinemia B. Familial Combined Hypolipidemia C. Tangier Disease (ABCA1 Deficiency) D. Primary Hypoalphalipoproteinemia
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5. In screening for hypercholesterplemia: Plasma lipid levels should be measured, preferably after a 12-h overnight fast, In all adults Guidelines suggest that screening of children between 9 and 11 years of age All of the above
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6. In diagnosing Dyslipidemia except : A critical first step in managing a lipoprotein disorder is to attempt to determine the class or classes of lipoproteins that are increased or decreased in the patient. Once the dyslipidemia is accurately classified, efforts should be directed to rule out any possible secondary causes A fasting glucose should be obtained in the initial workup of all subjects with an elevated TG level. Liver function tests should not be performed to rule out hepatitis and cholestasis.
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7. Definition of Severe Hypertriglyceredemia A. If the fasting plasma TG level is >750 mg/dL, the patient may have chylomicronemia. B. If the elevated TG levels are persistent and the total cholesterol-to-TG ratio is >10 C. If the levels of LDL-C are very high (greater than a ninety-fifth percentile for age and sex)
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8. The major goals in the clinical management of lipoprotein disorders are: A. prevention of acute pancreatitis in patients with severe hypertriglyceridemia B. prevention of CVD and related cardiovascular events. C. Both
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9. MANAGEMENT OF SEVERE HYPERTRIGLYCERIDEMIA TO PREVENT PANCREATITIS except A. It is generally considered appropriate medical practice to intervene in patients with TGs >500 mg/ dL in order to reduce the risk of pancreatitis B. Lifestyle modification C. Decreased Alcohol intake D. Smoking
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10. Pharmacologic Therapy for Hypercholesterolemia A. statin being first-line therapy B. depends on the level of TG as well as the level of cardiovascular risk C. TGs >500 mg/ dL