1. c.Given this patient’s age and risk factors, it was appropriate to proceed directly to a full (fasting) lipid profile. Individuals with a high overall or global cardiovascular disease risk assessment (e.g., 10-year risk of 20% or greater) require more aggressive risk factor assessment and consideration of modification. Normal serum cholesterol concentration is defined as a value less than 200   mg/dL by NCEP criteria. Any level above 200   mg/dL is considered high unless the HDL cholesterol is high enough to give a normal ratio of TC/HDL. The question of which patients should be screened for hypercholesterolemia continues to be debated. The fourth (most recent) USPSTF report recommended the following: (1) all men aged 35   years or older and all women aged 45   years or older should be screened routinely for lipid disorders (this extends the recommendations of the second USPSTF, which recommended that adults not be screened until age 65   years); (2) younger adults—men aged 20 to 35   years and women aged 20 to 45   years—should be screened if they have other risk factors for heart disease (these risk factors include tobacco use, diabetes, a family history of heart disease or high cholesterol, or high blood pressure; this recommendation expands on the recommendations of the second USPSTF, which focused on screening middle-aged men and women); and (3) clinicians should measure HDL in addition to TC or LDL. The USPSTF found insufficient evidence to recommend for or against measurement of triglycerides. In addition, the current recommendation is to screen with a nonfasting sample.

2. b.The National Cholesterol Education Program Adult Treatment Panel III (NCEP–ATP III) guidelines (2004) define high blood cholesterol as equal to or greater than the following: (1) TC, 200   mg/dL; and (2) LDL, 130   mg/dL. These recommendations are in a state of flux at present, and attention to additional future literature should be considered.

3. c.The most important lipid risk factor for CAD is an elevated LDL level. The second most important lipid risk factor is a depressed HDL level.

4. b.The five major risk factors for CAD are (1) having hypertension, (2) smoking, (3) having diabetes, (4) being older than 45   years in men and older than age 55   years in women, and (5) having a family history of MI in a first-degree relative (male relative younger than 55   years or female relative younger than 65   years) (Strength of Evidence    =    A). Obesity is not a specific risk factor but is strongly associated with the conditions that are major risk factors (Strength of Evidence    =    C).

5. e.The following conditions are considered CAD risk factor equivalents: peripheral arterial disease, diabetes mellitus, abdominal aortic aneurysm, and symptomatic carotid artery disease (history of cerebrovascular accident, transient ischemic attack, or carotid disease of more than 50% obstruction of the internal carotid artery), or 2 + cardiac risk factors with a 10-year risk assessment of more than 20% (Strength of Evidence    =    A).

6. a.An elevated triglyceride level, defined as 250   mg/dL or more, is often observed in people with diabetes with poor glucose control. Weight loss and a low-carbohydrate and low-fat diet are recommended for lifestyle treatment of hypertriglyceridemia. An elevated triglyceride level is associated most closely with an elevated VLDL or depressed HDL level. TC may be elevated with high triglyceride levels but can also be in the normal range.

7. c.An LDL level is considered elevated according to NCEP guidelines when it is higher than 130   mg/dL. Another method of assessment is based on the Framingham risk assessment. If the 10-year cardiac risk assessment is less than 10%, an LDL level of more than 160   mg/dL is high. If the 10-year risk assessment is 10% to 20%, the LDL level is considered high when it is more than 130   mg/dL. If the 10-year risk assessment is greater than 20%, the LDL level is considered elevated when it is more than 100   mg/dL (Strength of Evidence    =    A).

8. e.The treatment of choice for hypercholesterolemia is diet therapy. The AHA has produced Step 1 and Step 2 diets. The Step 1 diet includes less than 30% of total calories from fat, less than 10% of calories from saturated fat, and less than 300   mg/day of cholesterol. The Step 2 diet includes less than 30% of total daily calories as fat, less than 7% of calories from saturated fat, and less than 200   mg/day of cholesterol. Management of hypercholesterolemia with drugs is indicated only after dietary treatment for a reasonable amount of time has failed to reduce the cholesterol level to a sufficiently low level, although there is a newfound sense of more aggressive treatment for primary as well as secondary prevention as the result of studies such as the Air Force/Texas Coronary Atherosclerosis Prevention Study and updates of the Framingham Heart Study as well as others. The current recommendations that diet therapy be continued for 6   months before drug therapy is started are often supplanted because these studies have shown conclusively that aggressive treatment of even low-risk middle-aged adults with statin therapy can reduce cardiac morbidity and mortality. These issues will continue to evolve and recommendations will be revised over time as studies mature.

9. e.Healthy lifestyle choices that reduce the risk of coronary events include diet, aerobic exercise, weight management, smoking cessation, aspirin therapy (Strength of Evidence    =    A), and multivitamin supplements with folic acid and plant stanol ester nutritional supplements (Strength of Evidence    =    B). The Food and Drug Administration permits food labels to indicate that daily use of plant stanol esters will help reduce LDL levels. These esters are produced by the esterification of the plant steroid stanol with canola oil, and they act by blocking the intestinal mucosal absorption of cholesterol. This reduces the serum LDL concentration to a modest degree but not the serum HDL concentration.

10. c.The drug class of choice for mild to moderate LDL elevation is one of the HMG-CoA reductase inhibitors on the market. These include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), atorvastatin (Lipitor), and rosuvastatin (Crestor). All patients who are prescribed HMG-CoA inhibitors should have not only a plasma lipid profile but also liver function tests and creatine kinase concentration at baseline and then after 12   weeks. If no further dose changes are made, liver function tests may be evaluated every 6   months and then yearly when the patient is stable. There is a low risk of myositis; therefore, creatine kinase levels should be measured as before and if patients report leg pain or muscle cramps. For patients taking rosuvastatin, attention to renal function is also a consideration. In patients with mild to moderate isolated LDL elevation (type IIa), plasma lipids may be normalized with 10 to 20   mg once daily of these agents. Patients with higher LDL levels may require higher doses of single-agent therapy or, alternately, multidrug therapy. With such therapy, LDL cholesterol levels may be lowered up to 40%, and triglyceride levels may be lowered 10% to 15%. There appears to be little change in the HDL level with statin therapy. All the previously mentioned drugs have been known to produce hepatic and skeletal muscle toxicity, insomnia, and weight gain. These side effects, however, are relatively uncommon, are dose related, and occur much more frequently in patients who are undergoing multidrug therapy (Strength of Evidence    =    A). Statins are best dosed at bedtime. According to NCEP, the drug of second choice for type IIa hyperlipoproteinemia is niacin.

The total daily dose (500-mg tablets) is up to 3   g. All patients taking niacin require monitoring of liver function tests and creatine kinase monthly for 3   months, then every 3   months for 6   months, and every 4 to 6   months thereafter. Niacin may decrease plasma LDL concentration by up to 35% and may decrease triglyceride levels by up to 75%; at the same time, it may increase HDL concentration by up to 100%. In addition, the apolipoprotein A level is decreased by up to 50%. Unfortunately, niacin has a considerable number of significant side effects, including induction of gastric irritation and gastritis; activation of long-dormant peptic ulcers; elevation of plasma uric acid levels, precipitating an attack of gout; elevation of blood glucose levels; exacerbation of diabetes; and, most commonly, cutaneous flushing, dry and even scaly skin, and, in rare instances, acanthosis nigricans.

Some of these nuisance side effects can be ameliorated by coadministration of aspirin or prescription of the long-acting formulation of niacin. Fortunately, all side effects disappear when the drug is discontinued.

Challenges have been made for the use of niacin, and understanding of its therapeutic benefits and attention to future literature is warranted. Binding resins, including cholestyramine (Questran) and colestipol (Colestid), are the drugs of third choice for patients with type IIa hyperlipoproteinemia. The dose ranges are 4 to 8   g once or twice daily for cholestyramine and 5 to 10   g once or twice daily for colestipol. Their advantages include an almost complete lack of absorption and the potential for systemic toxicity that goes with it. Their disadvantages include an unpleasant grittiness and multiple gastrointestinal side effects, including abdominal bloating, abdominal pain, sometimes severe constipation, and gastrointestinal bleeding.

Because resins may decrease the absorption of other drugs, they and other drugs should be taken 2 hours apart. For some patients with complex drug regimens, this option may become impossible because of variable absorption of necessary drugs (e.g., patients with HIV infection receiving highly active antiretroviral therapy with dyslipidemia).

11. d.Vitamin E, although popular as an antioxidant, has not been shown to favorably or unfavorably alter the course of CAD. Dietary fiber also has no beneficial effect on heart disease, but it does show favorable effect on colorectal disease. Hormone replacement therapy was shown to increase the risk of CAD by the Women’s Health Initiative. However, primary and secondary prevention trials have shown that aspirin decreases CAD risk.

12. e.Separate and independent risk factors for CAD include increased LDL concentration (most important lipid risk factor), decreased HDL (second most important lipid risk factor), increased TC, and increased triglyceride concentration.

13. e.Nifedipine, a calcium channel blocker, and fosinopril, an angiotensin-converting enzyme inhibitor, are the only drugs listed that do not have an adverse effect on plasma lipids. (Angiotensin receptor blockers are also neutral with respect to plasma lipids, and alpha blockers appear to have a beneficial effect on HDL levels.) The beta blocker listed, metoprolol, and hydrochlorothiazide adversely affect plasma lipid levels.

14. d.As mentioned previously, the treatment of first choice for hyperlipidemia is diet. The AHA’s Step 1 diet consists of 300   mg daily of cholesterol, 30% of calories from total fat, and 10% of calories from saturated fat. The Step 2 diet is limited to 200   mg of cholesterol, 30% of calories from total fat, and 7% of calories from saturated fat.

15. e.Fish and fish oil supplements may reduce plasma lipid levels (especially triglycerides), inhibit platelet aggregation, decrease blood pressure and viscosity, and increase HDL cholesterol concentration (as well as having a salutary effect on synovial fluid). The active ingredients are the long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Well-controlled long-term studies conducted by the Brigham and Women’s Hospital and the Harvard Public School of Health and released in 2002 showed an 81% decrease in sudden cardiac-related death risk in men and a 34% decrease in women who consumed fish on a regular basis. Female nurses who consumed fish at least once a week also were found to have a 25% decline in nonfatal heart attacks and a significant decline in deaths in general. The authors thought that both fish and fish oil supplements had a positive effect. However, the benefit of fish oil supplements for general use remains more controversial, perhaps because it may not generally be appreciated that efficient absorption requires the presence of other nutrients, particularly additional lipid. In addition, these polyunsaturated fatty acids readily auto-oxidize.

The essential 18-carbon omega-3 fatty acid linolenic acid (also known as alpha-linolenic acid) can be converted to the 20-carbon eicosapentaenoic acid, which in turn is converted to the 22-carbon docosahexaenoic acid and as a consequence can substitute for fish oils. The typical U.S. diet, however, tends to limit this conversion because the linoleic/linolenic acid ratio in the diet is too high. This conversion may also be inhibited by other fatty acids; trans fatty acids in particular have been implicated (Strength of Evidence    =    A). Unfortunately, the distribution of alpha-linolenic acid is limited. Studies suggest that the optimal linoleic/linolenic acid ratio is between 5 and 10 to 1. The oils produced from flaxseed, walnuts, rapeseed (canola), safflower, soybean, and wheat germ are the only natural substances with these fatty acids in this optimal range. The best way to ensure that the oils are not partially oxidized is to consume them in the foods from which they are derived.

16. b.The drug of choice for most cases of hypertriglyceridemia is gemfibrozil or another fibric acid derivative. Hypertriglyceridemia may be associated with type IIa, type IIb, type III, or type IV hyperlipoproteinemia. The usual dose of gemfibrozil is 0.6   g twice a day. Gemfibrozil will decrease hypertriglyceridemia by 40% to 80% and will potentially increase HDL by 10% to 20%. Combining a reductase inhibitor with gemfibrozil has become a commonly used regimen, although it was once feared. This combination still should be used with caution and may be tolerated if a low dose of one drug is given 6 to 12 hours apart from a low dose of the other (e.g., pravastatin, 10 to 20   mg in the morning, with gemfibrozil, 600   mg in the evening). This dosing regimen may, however, limit the effectiveness of this option. Laboratory monitoring of this therapeutic option is necessary and with vigilance because of an increase in both hepatic and myopathic side effects. In high-risk patients, these risks are frequently outweighed substantially by the cardiac risk factor reduction.

17. b.Hypothyroidism, lupus, pregnancy, oral contraceptive use, and nephritic syndrome are associated with elevations of cholesterol. Cirrhosis is usually associated with a decrease in cholesterol.

18. b.The USPSTF recommends general screening at the age of 35   years for men and 45   years for women and targeted screening in adults aged 20 to 45   years. If HDL cholesterol concentration is more than 60   mg/dL, one risk factor may be subtracted from the CAD risk factor total. Start a statin medication in a patient with diabetes mellitus with an LDL cholesterol level of 100   mg/dL or more. The Heart Protection Study suggests that statins may even be beneficial in people with diabetes who have LDL values of less than 100   mg/dL. LDL cholesterol can be calculated as [total cholesterol − (triglycerides/5    +    HDL cholesterol)]. (Again, statin medications are best given in the evening, except for those with long half-lives.)