Hyperlipidemias and Cardiovascular Disease

Course #90842 - $40 • 10 Hours/Credits


Study Points

  1. Discuss the incidence of cardiovascular disorders, expected epidemiological trends, and relevance to society and healthcare systems.
  2. Discuss the relevance of hyperlipidemias in the etiology of atherosclerosis and cardiovascular diseases.
  3. Identify risk factors for hyperlipidemias.
  4. Describe the exogenous and endogenous pathways of lipid synthesis and metabolism.
  5. Describe the various types of lipoproteins.
  6. Evaluate lipid profiles and identify the most clinically relevant types of hyperlipidemias.
  7. Analyze the importance of lifestyle modification in managing hyperlipidemias.
  8. Discuss the targeting of specific steps in lipid synthesis and metabolism related to the mechanism of action of drugs that inhibit cholesterol absorption in the intestine.
  9. Describe the therapeutic efficacy and indications of fibrates, statins, and nicotinic acid derivatives.
  10. Determine the role of fish oil derivatives and sterols and stanols in the management of hyperlipidemias.
  11. Identify patients at risk for coronary heart disease and outline the evidence-based guidelines for the treatment of these patients.

    1 . Cardiovascular disease (CVD) accounts for approximately what percentage of deaths in the United States?
    A) 10%
    B) 25%
    C) 31%
    D) 55%

    INTRODUCTION AND EPIDEMIOLOGY OF CARDIOVASCULAR DISEASES

    Cardiovascular disease (CVD) is the leading cause of death in developing countries and accounts for 30.8% of all deaths in the United States and 47% of deaths in Europe [1,2]. It has been estimated that by 2030 CVD will account for approximately 23 million deaths worldwide [3].

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    2 . Approximately what percentage of Americans 20 years of age or older have total blood cholesterol levels in excess of 240 mg/dL?
    A) 5%
    B) 8%
    C) 12%
    D) 15%

    INTRODUCTION AND EPIDEMIOLOGY OF CARDIOVASCULAR DISEASES

    Data published in the National Health and Nutrition Examination Survey revealed that an estimated 12.1% of Americans 20 years of age and older have total blood cholesterol concentrations of 240 mg/dL (6.2 mmol/L) or greater, which are associated with high risk of cardiovascular morbidity and mortality [15].

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    3 . Which of these statements regarding atherosclerosis is TRUE?
    A) Atherosclerosis is initiated during middle-age.
    B) Atherosclerosis is a process that targets small sized arteries.
    C) Atherosclerosis is rapidly accelerated by genetic and environmental factors.
    D) All of the above

    ETIOLOGY OF ATHEROSCLEROSIS

    Atherosclerosis is a chronic inflammatory process that targets medium- and large-sized arteries. This process is initiated during childhood and progresses slowly with age. However, the condition is rapidly accelerated by a variety of genetic and environmental factors, and hyperlipidemia is a major risk factor in the pathogenesis and progression of atherosclerosis [12,14,26,27].

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    4 . All of the following are progressive stages of atherosclerosis, EXCEPT:
    A) plaque formation.
    B) plaque disruption.
    C) fatty streak formation.
    D) high density lipoprotein.

    ETIOLOGY OF ATHEROSCLEROSIS

    The pathological processes underlying atherosclerosis can be categorized into three progressive stages: fatty streak formation, plaque formation, and plaque disruption [12,27,28,29,30,31].

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    5 . Which of the following is NOT considered a biomarker for CVD?
    A) Age
    B) Lipoprotein(a)
    C) C-reactive protein
    D) Hyper-homocysteinemia

    RISK FACTORS FOR HYPERLIPIDEMIA

    As noted, hyperlipidemia has been established as a main risk factor in the development of atherosclerosis and CVD. Together with obesity, hypertension, diabetes, smoking, and physical inactivity, hyperlipidemia is a known modifiable risk factor of CVD. Additionally, several biomarkers, including C-reactive protein (CRP), hyper-homocysteinemia, and lipoprotein(a), are also considered modifiable risk factors of CVD. Modifiable risk factors play a major role in the pathogenesis of CVD because they activate the endothelium and stimulate the release of proinflammatory mediators and cell surface adhesion molecules. Because modifiable risk factors account for up to 90% of population-attributable cardiac risk, regulation of these factors has a beneficial effect on the primary and secondary prevention of CVD [11,12].

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    6 . The role of lipoprotein(a) in atherogenesis relates to a variety of mechanisms, EXCEPT:
    A) low affinity for the LDL-receptor.
    B) decelerated smooth cell proliferation.
    C) enhanced capacity to traverse the arterial endothelium.
    D) inhibition of fibrinolysis by preventing the transformation of plasminogen to plasmin.

    RISK FACTORS FOR HYPERLIPIDEMIA

    Numerous clinical studies have also revealed that high levels of lipoprotein(a) are associated with significant increases in CVD [12,27,31,35,46,47]. Lipoprotein(a) is a subtype of LDL that includes apoprotein A (Apo A) in its structure. The role of lipoprotein(a) in atherogenesis relates to a variety of mechanisms including inhibition of fibrinolysis by preventing the transformation of plasminogen to plasmin, enhanced capacity to traverse the arterial endothelium, and low affinity for the LDL-receptor mediated clearance from circulation [46]. High lipoprotein(a) concentrations (greater than 30 mg/dL) in patients with an elevated total cholesterol:HDL ratio (greater than 5.5) or other major risk factors indicates the need for a more aggressive therapy to further lower LDL [24,48].

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    7 . Dietary lipids account for what percentage of calories in western diets?
    A) 10% to 20%
    B) 20% to 30%
    C) 30% to 40%
    D) 40% to 50%

    AN OVERVIEW OF LIPIDS

    Dietary lipids provide 30% to 40% of calories in Western diets. With the exception of the essential fatty acids (e.g., linoleic, linolenic), most lipids can also be synthesized by humans. Triglycerides, specifically, account for more than 95% of dietary lipid intake. Cholesterol from animal sources and small amounts of plant sterols comprise the majority of dietary lipid intake. Free fatty acids, phospholipids, and fat-soluble vitamins account for the remaining lipids from dietary sources [35,49,52].

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    8 . What is the main site of lipid transformation and absorption?
    A) Mouth
    B) Stomach
    C) Small intestine
    D) Large intestine

    AN OVERVIEW OF LIPIDS

    Dietary fat is digested by enzymes produced in the mouth, stomach, and pancreas. The small intestine is the main site of lipid transformation and absorption. In the small intestine, triglycerides are hydrolyzed by gastric and pancreatic lipases, phospholipids are transformed by phospholipase A2 into lysophospholipids and fatty acids, and cholesterol is hydrolyzed by bile salts and pancreatic hydrolase (also known as cholesterol esterase).

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    9 . Which of the following statements regarding chylomicrons is FALSE?
    A) Chylomicrons are only synthesized in the intestine.
    B) Chylomicrons are composed mainly of triglycerides.
    C) Chylomicrons are large lipoproteins very rich in lipids.
    D) Chylomicrons have the highest protein content of any lipoprotein.

    AN OVERVIEW OF LIPOPROTEINS

    Chylomicrons are large lipoproteins 75–1,200 nm in diameter that are very rich in lipids (98% content), mainly triglycerides (83%) and cholesterol (8%), and have the lowest protein content (2%) of all lipoproteins. Chylomicrons are only synthesized in the intestine and are produced in large amounts during fat ingestion [52]. In normolipidemic individuals they are present in the plasma for 3 to 6 hours after fat ingestion and are absent after 10 to 12 hours fasting [14].

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    10 . Increased LDL levels can result from
    A) a deficiency of estrogens.
    B) a deficiency of thyroid hormones.
    C) genetic mutations of either the LDL receptor or Apo B-100.
    D) All of the above

    AN OVERVIEW OF LIPOPROTEINS

    Genetic mutations of either the LDL receptor or Apo B-100 alter the effectiveness of the binding and increase the plasma concentration of LDL. Familial hypercholesterolemia and familial defective Apo B-100 are examples of clinical conditions that result from these genetic mutations [36,76]. Homozygotes for familial hypercholesterolemia inherit two mutant LDL receptor genes and present with a 6- to 10-fold elevation in plasma LDL from birth. These patients suffer from advanced CHD starting in early childhood [67,77].

    The expression of LDL receptors in the liver is also regulated by the intracellular enzyme HMG-CoA reductase. Inhibition of HMG-CoA reductase, for example by the administration of statins, not only results in direct inhibition of the intracellular synthesis of cholesterol but indirectly increases the expression of LDL receptors and therefore promotes the LDL-receptor-mediated removal of circulating cholesterol.

    The LDL receptor is also relevant from a clinical perspective because both thyroid hormones and estrogens stimulate its expression in the liver [74,78]. Consequently, deficiencies of these hormones decrease the availability of LDL receptors and result in increased concentrations of circulating LDL and increased risk of CVD [14,74].

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    11 . Which of the following statements regarding HDLs is TRUE?
    A) HDLs are the largest lipoproteins.
    B) The protein content of HDLs is 33%.
    C) HDL removes cholesterol from the periphery and transports it to the kidneys.
    D) The two most important subclasses of HDL express either Apo A-II alone or both Apo A-I and A-II.

    AN OVERVIEW OF LIPOPROTEINS

    HDLs are the smallest (5–12 nm in diameter) but the densest lipoproteins (33% protein content). HDL removes cholesterol from the periphery and transports it to the liver [52]. HDLs are a heterogeneous population classified based on size, density, and apoprotein content. The two most important subclasses of HDL express either Apo A-I alone or both Apo A-I and A-II, but the clinical relevance of the various subtypes is unknown [81].

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    12 . Research has shown that moderate-to-high HDL levels may help to prevent CVD. The main goal for patients with hyperlipidemias should be to
    A) increase HDL levels.
    B) decrease LDL levels.
    C) increase triglyceride levels.
    D) All of the above

    AN OVERVIEW OF LIPOPROTEINS

    In vitro and in vivo studies have revealed that HDL has anti-inflammatory and antioxidant properties and inhibits atherogenesis. It has been suggested that high levels of HDL have a protective effect on the development of atherosclerosis and CVD [81,85].

    However, authors of a systematic review of clinical studies concluded that "simply increasing the amount of circulating HDL does not necessarily confer cardiovascular benefits" and that reduction of LDL should remain "the primary goal for lipid-modifying interventions" [86]. Other researchers concluded that raising endogenous HDL levels in humans to reduce the development of atherosclerosis "has yet to be established conclusively" [81]. Together, these studies further support the recommendation that lowering LDL should remain the target goal for patients with hyperlipidemia and/or at risk for CVD-related conditions [22,23].

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    13 . The primary goal of lipid therapy in high-risk patients is to reduce LDL cholesterol to at least less than 100 mg/dL, and optimally to less than
    A) 50 mg/dL.
    B) 60 mg/dL.
    C) 70 mg/dL.
    D) 80 mg/dL.

    CLASSIFICATION AND CLINICAL RELEVANCE OF HYPERLIPIDEMIAS

    From a clinical perspective, the primary goal of lipid therapy in high-risk patients, including lifestyle changes and pharmacotherapy, is aimed at reducing LDL cholesterol to at least less than 100 mg/dL (2.58 mmol/dL) or optimally to less than 70 mg/dL (1.80 mmol/dL) [22,23,63,87,88,206,207]. Baseline cholesterol values also vary by geography and among ethnic minority populations. For example, in the Western population cholesterol values are about 20% higher than in the Asian population [63].

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    14 . As primary hyperlipidemia progresses, the following signs and symptoms develop, EXCEPT:
    A) obesity.
    B) lipemic plasma.
    C) eruptive xanthomas.
    D) severe hypertriglyceridemia.

    CLASSIFICATION AND CLINICAL RELEVANCE OF HYPERLIPIDEMIAS

    At the early stages, primary hyperlipidemias are asymptomatic. However, as the disease progresses, a constellation of signs and symptoms develop, such as eruptive xanthomas (located on the trunk, back, buttocks, elbows, knees, hands, and feet), severe hypertriglyceridemia (greater than 2,000 mg/dL), lipemic plasma (i.e., plasma develops a creamy supernatant when incubated overnight), and lipemia retinalis (i.e., creamy white-colored blood vessels in the fundus) often associated with premature CHD or peripheral vascular disease [35,88,93].

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    15 . With an incidence greater than 25% in the United States, the most common form of hyperlipidemia is
    A) atherogenic dyslipidemia.
    B) familial hypertriglyceridemia.
    C) familial hypercholesterolemia.
    D) polygenic hypercholesterolemia (or nonfamilial hypercholesterolemia).

    CLASSIFICATION AND CLINICAL RELEVANCE OF HYPERLIPIDEMIAS

    Polygenic hypercholesterolemia, also known as nonfamilial hypercholesterolemia, is the most common form of hyperlipidemia, with a prevalence of more than 25% in the American population [95]. Polygenic hypercholesterolemia is a typical example of the combination of multiple genetic deficiencies that result in decreased activity of the LDL receptor and reduction of LDL clearance. This underlying genetic susceptibility, not yet completely understood, becomes apparent with dietary intake of saturated fats, obesity, and sedentary lifestyle. Twenty percent of polygenic hypercholesterolemia patients have a family history of CHD. Patients present with mild-to-high increases in total cholesterol (250–350 mg/dL or 6.5–9.0 mmol/L) and LDL (130–250 mg/dL or 3.33–6.45 mmol/L). A combination of lifestyle changes (e.g., reduction in saturated fat) and lipid-lowering drugs (e.g., statins, bile acid sequestrants, ezetimibe, niacin) effectively control the condition [31,96].

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    16 . Secondary hyperlipidemias can be precipitated by the use of certain medication treatments. These treatments include estrogen therapy, atypical antipsychotics, corticosteroids, and
    A) statins.
    B) fibrates.
    C) thiazides.
    D) antioxidants.

    CLASSIFICATION AND CLINICAL RELEVANCE OF HYPERLIPIDEMIAS

    Secondary hyperlipidemias can also be associated with a number of drug-induced conditions such as estrogen therapy (increased triglycerides and increased total cholesterol), atypical antipsychotics (increased triglycerides), corticosteroids (increased total cholesterol), selective β-blockers without intrinsic sympathetic activity or α-antagonism (increased total cholesterol and decreased HDL), and thiazides (modest increase in total cholesterol and LDL) [63,102].

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    17 . Secondary hyperlipidemia with elevated cholesterol is the main dyslipidemia in patients with
    A) obesity.
    B) alcohol abuse.
    C) chronic renal failure.
    D) hormone replacement therapy.

    CLASSIFICATION AND CLINICAL RELEVANCE OF HYPERLIPIDEMIAS

    In summary, secondary hyperlipidemias with elevated triglycerides are the primary lipid abnormality in patients with obesity, diabetes, alcohol abuse, hormone replacement therapy, and atypical antipsychotic therapy. Secondary hyperlipidemias with elevated cholesterol are the main dyslipidemia in patients with chronic renal failure, hypothyroidism, and typical β-blocker use (e.g., propranolol, atenolol).

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    18 . The NCEP-ATP III therapeutic lifestyle change guidelines for patients with hyperlipidemias recommends
    A) a low fat diet (maximum of 15% of total calories) with less than 5% of calories derived from saturated fats, and 200 mg or less per day of cholesterol.
    B) a low fat diet (maximum of 15% of total calories) with less than 7% of calories derived from saturated fats, and 200 mg or less per day of cholesterol.
    C) a low fat diet (maximum of 25% of total calories) with less than 7% of calories derived from saturated fats, and 200 mg or less per day of cholesterol.
    D) a low fat diet (maximum of 30% of total calories) with less than 10% of calories derived from saturated fats, and 400 mg or less per day of cholesterol.

    LIFESTYLE MODIFICATION

    The therapeutic lifestyle change guidelines developed by the NCEP-ATP III recommend a diet low in fat (a maximum of 25% of total calories versus the 35% in the average North American diet), with less than 7% of calories derived from saturated fats and 200 mg or less per day of cholesterol (compared to the 400 mg/day in the average North American diet) [22]. A successful dietary approach to lipid lowering requires instruction by a dietitian or other knowledgeable healthcare professional. In brief, there are several principles that highlight the most important instruction to be provided to patients [22]:

    • Reduce intake of high-fat food, particularly foods high in saturated fats (e.g., fast food and processed food) and trans fatty acids (e.g., processed chips, cakes, cookies).

    • Replace saturated fats from meat products and oils used in processed and fast foods (e.g., lard, palm oil, coconut oil) with unsaturated fats, especially mono-unsaturated fats (e.g., canola oil, olive oil).

    • Replace high-fat dairy products with low-fat alternatives (e.g., skim milk, skim cottage cheese, non-fat yogurt).

    • Increase intake of fish and/or poly-unsaturated fats (e.g., fish omega-3 and plant omega-6 polyunsaturated fatty acids).

    • Increase intake of foods rich in complex carbohydrates and fiber (e.g., whole grains, vegetables, legumes, fruit, psyllium).

    • Limit alcohol consumption to no more than two drinks per day for men and one drink per day for women. Ideally, alcohol should be consumed with meals. Higher alcohol intake increases triglycerides.

    • Reduce sodium and sugar intake.

    • Achieve acceptable body weight (body mass index between 18.5 and 24.9).

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    19 . Which of the following statements regarding lipid management through lifestyle change is TRUE?
    A) Lipid lowering goals can usually be achieved on one's own.
    B) Lipid lowering through diet and exercise will not reduce the risk for CVD and mortality.
    C) Successful lipid control usually requires instruction by a dietitian or other knowledgeable healthcare professional.
    D) In patients with high cardiovascular risk and/or very high LDL, medication therapy should be initiated if lifestyle changes are not effective within a two- to three- month period.

    LIFESTYLE MODIFICATION

    The therapeutic lifestyle change guidelines developed by the NCEP-ATP III recommend a diet low in fat (a maximum of 25% of total calories versus the 35% in the average North American diet), with less than 7% of calories derived from saturated fats and 200 mg or less per day of cholesterol (compared to the 400 mg/day in the average North American diet) [22]. A successful dietary approach to lipid lowering requires instruction by a dietitian or other knowledgeable healthcare professional. In brief, there are several principles that highlight the most important instruction to be provided to patients [22]:

    • Reduce intake of high-fat food, particularly foods high in saturated fats (e.g., fast food and processed food) and trans fatty acids (e.g., processed chips, cakes, cookies).

    • Replace saturated fats from meat products and oils used in processed and fast foods (e.g., lard, palm oil, coconut oil) with unsaturated fats, especially mono-unsaturated fats (e.g., canola oil, olive oil).

    • Replace high-fat dairy products with low-fat alternatives (e.g., skim milk, skim cottage cheese, non-fat yogurt).

    • Increase intake of fish and/or poly-unsaturated fats (e.g., fish omega-3 and plant omega-6 polyunsaturated fatty acids).

    • Increase intake of foods rich in complex carbohydrates and fiber (e.g., whole grains, vegetables, legumes, fruit, psyllium).

    • Limit alcohol consumption to no more than two drinks per day for men and one drink per day for women. Ideally, alcohol should be consumed with meals. Higher alcohol intake increases triglycerides.

    • Reduce sodium and sugar intake.

    • Achieve acceptable body weight (body mass index between 18.5 and 24.9).

    Instructions to patients should not be presented as a list of "foods to avoid" but rather should provide dietary alternatives and teach the patients how to make appropriate dietary choices and control portions. A balanced diet, particularly in the modality known as the Mediterranean diet, is associated with a significant reduction in cardiovascular events and mortality [103,104,105]. The Mediterranean diet is characterized by meals predominately consisting of vegetables/fruits, lean protein, and healthy fats (e.g., olive oil) and the moderate consumption of wine.

    Physical activity stimulates the activity of lipoprotein lipase in adults as well as in children, lowers triglycerides and VLDL, and promotes cardiovascular fitness and weight loss [31,106]. As such, patients should be encouraged to engage in moderate-intensity physical activity on most days of the week unless contraindicated.

    Although dietary changes should always be included in the treatment of hyperlipidemias, the length of time given to lifestyle changes prior to initiation of pharmacotherapy remains controversial. In patients with low cardiovascular risk, it has been proposed that the efficacy of dietary and other lifestyle changes can be assessed in two to three visits over a two- to three-month period. However, pharmacotherapy should be promptly initiated when lifestyle changes are not effective. In patients with high cardiovascular risk or very high LDL (≥200 mg/dL or ≥5.2 mmol/L) drug therapy and lifestyle changes should be initiated immediately [35,107].

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    20 . Bile acids are the source of what percentage of cholesterol in the intestine?
    A) 25%
    B) 50%
    C) 75%
    D) 100%

    LIPID-LOWERING MEDICATIONS

    Bile acid-binding resins, also known as bile acid sequestrants, are cationic polymers that bind to the negatively charged bile acids in the lumen of the intestine. The bile-acid complex cannot be absorbed by the intestinal mucosa and is subsequently eliminated in the feces [114]. Bile acids are the source of 75% of cholesterol in the intestine, and inhibition of their reabsorption effectively disrupts chylomicron formation and decreases the availability of cholesterol and triglycerides in the liver.

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    21 . The cholesterol absorption inhibitor ezetimibe can increase the efficacy of what other treatment by 25%?
    A) Statins
    B) Niacin
    C) Fish oil
    D) Fibrates

    LIPID-LOWERING MEDICATIONS

    Ezetimibe selectively targets and inhibits the transporter NPC1L1, preventing the uptake of cholesterol and phytosterol across the intestinal lumen. Ezetimibe is indicated as adjunctive therapy to diet for the reduction of total cholesterol, LDL, and Apo B in patients with primary (heterozygous familial and nonfamilial) hyperlipidemia [117,118]. It lowers LDL by 15% to 20% and causes minimal increases in HDL, but its beneficial effect on prevention of CHD remains unclear. This agent is synergistic with statins and, if taken in conjunction, can lower LDL by up to 25% in addition to the results obtained by statins alone [118,213]. Ezetimibe is available in a combination formulation with the statin simvastatin under the brand name Vytorin. A second combination formulation combining ezetimibe with the statin atorvastatin, brand name Liptruzet, received U.S Food and Drug Administration (FDA) approval in 2013. However, Liptruzet was recalled in 2014 for packaging issues and discontinued in 2016 [117,118,119,210].

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    22 . Of the following, which statin is among the most effective in its class?
    A) Lovastatin
    B) Fluvastatin
    C) Pravastatin
    D) Simvastatin

    LIPID-LOWERING MEDICATIONS

    The first statin to be tested and approved for clinical use, lovastatin, was isolated from the mold Aspergillus terreus, and pravastatin and simvastatin are chemically modified derivatives of the original molecule. Atorvastatin, fluvastatin, and rosuvastatin are synthetic compounds with distinct molecular structures. Lovastatin, pravastatin, and simvastatin are inactive prodrugs that require hydroxylation in the liver into their active forms. Although all statins are clinically very effective, rosuvastatin, atorvastatin, and simvastatin have the highest drug efficacy in this class (Table 5).

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    23 . In addition to lowering lipid levels, statins are thought to have all of the following pleiotropic effects, EXCEPT:
    A) neuroprotection.
    B) modulation of endothelial function.
    C) an increase in vascular inflammation.
    D) immunomodulation by inhibition of major histocompatibility complex II expression.

    LIPID-LOWERING MEDICATIONS

    In addition to the lipid-lowering actions of statins, studies suggest that the drugs are also implicated in a number of additional actions known as pleiotropic effects. This includes modulation of endothelial function, decrease in vascular inflammation, neuroprotection, and immunomodulation by inhibition of major histocompatibility complex II expression, which is upregulated in patients with myocarditis, multiple sclerosis, and rheumatoid arthritis [126,127,128]. Statins have been linked to a reduction in the risk of developing Alzheimer disease independent of the drugs' lipophilicity [128].

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    24 . To achieve optimum lipid control in dyslipidemic patients, the initial dosage of any statin should be based on which factor?
    A) Age
    B) Cost
    C) LDL goal
    D) Body mass

    LIPID-LOWERING MEDICATIONS

    The lowest recommended starting dose for all statins is set with the goal to decrease LDL by 20% to 30%. Dyslipidemic patients, however, often remain undertreated because the initial dose is not titrated to achieve their target LDL goal. Several sources advise that the initial dosage should be determined based on the target LDL goal for that patient [14]. As an example, for a patient with an LDL level of 170 mg/dL (4.52 mmol/L) to reach the 100 mg/dL (2.58 mmol/L) desirable baseline, a 41% reduction is required. Accordingly, rosuvastatin 10 mg or atorvastatin 40 mg would be appropriate choices. However, higher doses of statins are associated with higher incidence of adverse effects, and the patient should be adequately monitored. Administration of statins with short half-lives (≤4 hours), which would include all but atorvastatin (13 to 16 hours) and rosuvastatin (19 hours), should be taken in the evening because the synthesis of cholesterol in the liver is maximal between midnight and 2 a.m. [14].

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    25 . Compared to statin monotherapy, bile acid-binding resin/statin combinations decrease LDL levels by what percentage?
    A) 8% to 10%
    B) 18% to 20%
    C) 20% to 30%
    D) 40% to 50%

    LIPID-LOWERING MEDICATIONS

    The combination of statins with other lipid-lowering drugs further improves the lipid-lowering outcome. The combination of simvastatin with ezetimibe lowers LDL by an additional 18% to 20% compared with simvastatin alone [130]. Administration of a statin with a bile acid-binding resin (e.g., cholestyramine, colestipol) produces 20% to 30% greater reductions in LDL than statins alone [131,132].

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    26 . Niacin, or nicotinic acid, is also known as what vitamin?
    A) Vitamin B3
    B) Vitamin D2
    C) Vitamin E2
    D) Vitamin B12

    LIPID-LOWERING MEDICATIONS

    Niacin, also known as nicotinic acid or vitamin B3, is a water-soluble vitamin that at physiologic levels is a substrate for nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), important cofactors in intermediary metabolism. Niacin is available in normal- or extended-release formulation as well as in conjunction with lovastatin (as Advicor).

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    27 . What is the most effective treatment option for raising HDL levels?
    A) Statins
    B) Niacin
    C) Fish oil
    D) Fibrates

    LIPID-LOWERING MEDICATIONS

    Niacin is the most effective drug available for raising HDL and is considered the drug of choice for patients with borderline to moderate increases in LDL and low HDL [30]. Niacin is a safe and cost-effective drug, and it is indicated as an adjunct to diet in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Frederickson phenotypes IIa and IIb) when the response to an appropriate diet and other nonpharmacologic measures has been inadequate [113].

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    28 . Omega-3 fatty acids are abundant in what dietary sources?
    A) Walnuts
    B) Fatty fish
    C) Canola oil
    D) All of the above

    LIPID-LOWERING MEDICATIONS

    Omega-3 polyunsaturated fatty acids are considered essential fatty acids because humans, as well as other mammals, are unable to synthesize these compounds efficiently. Eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are omega-3 polyunsaturated fatty acids derived from alpha-linolenic acid (ALA). Although humans are able to transform negligible amounts of ALA into EPA and DHA (<1%), dietary supplementation is the only physiologically relevant source [151]. Omega-3 fatty acids EPA and DHA are abundant in fatty fish, such as salmon, mackerel, sardines, trout, and herring, and other seafood sources, as well as in walnuts and canola, flaxseed, and linseed oils. Vegetable oils such as soybean, corn, sunflower, safflower, and cotton seed oils are good dietary sources of omega-6 fatty acids, which will be discussed in detail later in this course [56,152,153,154].

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    29 . Because they can be synthesized in the body, which of these fatty acids are considered non-essential?
    A) Omega-3 fatty acids
    B) Omega-6 fatty acids
    C) Omega-9 fatty acids
    D) None of the above

    LIPID-LOWERING MEDICATIONS

    Omega-6 polyunsaturated fatty acids such as gamma-linoleic acid (GLA) are derived from linoleic acid. Omega-9 polyunsaturated fatty acids, unlike omega-3 and omega-6, are non-essential because they can be synthesized in humans. The most relevant omega-9 fatty acid is oleic acid, which is present in olive oil, and supplementation is not required.

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    30 . According to the NCEP-ATP III, patients at high risk for CHD should be considered for drug therapy if they have an LDL level greater than or equal to
    A) 70 mg/dL.
    B) 100 mg/dL.
    C) 130 mg/dL.
    D) 160 mg/dL.

    CLINICAL GUIDELINES FOR THE TREATMENT OF HYPERLIPIDEMIAS

    NCEP-ATP III GUIDELINES FOR TREATMENT OF HYPERLIPIDEMIA

    Risk CategoryBegin Lifestyle Changes If:Consider Drug Therapy If:LDL Goal
    High: CHD or CHD equivalents (10-year risk >20%)LDL >100 mg/dL (2.58 mmol/L)LDL >100 mg/dL (2.58 mmol/L) (drug optional if <100 mg/dL [< 2.58 mmol/L])<100 mg/dL; <70 mg/dL optional
    Moderate high: >2 risk factors with 10-year risk 10 to 20%LDL >130 mg/dL (3.36 mmol/L)LDL >130 mg/dL (3.36 mmol/L)<130 mg/dL; <100 mg/dL optional
    Moderate: >2 risk factors with 10-year risk <10%LDL >130 mg/dL (3.36 mmol/L)LDL >160 mg/dL (4.13 mmol/L)<130 mg/dL; <100 mg/dL optional
    Lower: 0–1 risk factorLDL >160 mg/dL (4.13 mmol/L)LDL >190 mg/dL (4.91 mmol/L) (drug optional if 160–189 mg/dL [4.13–4.88 mmol/L])<160 mg/dL
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