Approach To High Cholesterol Definitions

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ATP III: The third report of the National Cholesterol Education Program Expert Panel on the Detection. Evaluation and Treatment of High Blood Cholesterol in Adults.

HDL cholesterol: High-density lipoprotein cholesterol.

LDL cholesterol: Low-density lipoprotein cholesterol.

Statin: Medication in the beta-hydroxy-beta-methylglutaryl-coenzyme A (HMG-CoA (-reductase inhibitor class. These are the most widely used medications for lowering LDL cholesterol.

Clinical Approach Determination of Lipid Goal

Numerous studies show that LDL cholesterol is a major risk for developing CHI) and that lowering LDL cholesterol can reduce this risk. For these reasons, the ATP III guidelines focus on the identification of those with high LDL cholesterol, the determination of that individual's risk of CHD, and development of an appropriate management plan to reach LDL cholesterol goals.

These guidelines recommend measuring lipid levels in all adults older than age 20 years every 5 years. The test performed can be either a fasting lipid panel (total. LDL and HDL cholesterol; triglycerides) or a nonfasting total and HDL cholesterol, with subsequent fasting lipid panel if either total cholesterol is over 200 mg/dL or if HDL cholesterol is less than 40 mg/dL. Table 35-1 lists the ATP III classification of lipid levels.

LDL cholesterol is the primary goal of management. Along with the presence of CHD or a CHD risk equivalent, the following five factors are considered to determine the LDL goal of a given individual:

Cigarette smoking

Hypertension (blood pressure >140/90 mm Hg or on antihypertensive medication)

• Age (>45 years for men; >55 years for women)

• Family history of premature CHD (male first-degree relative <55 years of age: female first-degree relative <65 years of age)

Table 35-1

ATP III CLASSIFICATION OF LIPID LEVELS

LDL Cholesterol (mg/dL)

<100 100-129 130-159 160-189 190 or greater

Optimal

Near optimal/above optimal

Borderline high

High

Very high

Total cholesterol (mg/dL)

<200 200-239 240 or greater

Desirable Borderline high High

HI)L cholesterol (mg/dL)

60 or greater

High

Information from ATP III repon.

A high HDL level is considered a negative risk, which removes one other risk factor from the total.

The LDL cholesterol goal is based upon the evaluation of these risks. A person with CHD or a CHI) risk equivalent has an LDL goal of 100 mg/dL or less. Someone with 0-1 identified risks has an IJ)L goal of 160 mg/dL or less. An individual with 2 or more risks should have an individual risk assessment performed, using a risk calculator. If someone has 2 or more risk factors and an individual risk of between 10% and 20%, that person's LDL goal is 130 mg/dL or (ess. However, if the individual risk is >20%, that person should be treated as having a CHD equivalent, with a goal LDL of <100 mg/dL (Table 35-2).

An update to the ATP 111 was issued in 2004 with an interpretation of some more recent clinical trials. This update suggests a "therapeutic option" of a very low LDL goal of <70 nig/dL for those patients at very high risk of CHI). This very-high-risk category includes people with CHD and either multiple major risk factors (especially diabetes), poorly controlled risk factors (especially smoking), multiple risk factors of metabolic syndrome (see Case 33), or an acute coronary syndrome.

Evaluation

When high blood cholesterol is identified, an investigation should be performed to evaluate for secondary causes of dyslipidemia. Included among these causes are diabetes, hypothyroidism, obstructive liver disease, and chronic renal failure. Consequently, a reasonable laboratory work-up includes a fasting

Table 35-2

MANAGEMENT GUIDELINES TO REACH LDL GOALS

Table 35-2

MANAGEMENT GUIDELINES TO REACH LDL GOALS

RISK

CATEGORY

LDL GOAL

LDL LEVEL TO START THERAPEUTIC LIFESTYLE CHANGE

LDL LEVEL TO CONSIDER MEDICATION

CHDorCHD equivalent

<100

(optional for 101-129)

2 or more risks factors

<130

10-yr risk <10% >190

0-1 risk factors

<160

>160

>190

All LDL levels in mg/dL. Information from ATP 111 report.

All LDL levels in mg/dL. Information from ATP 111 report.

blood glucose, thyroid-stimulating hormone (TSH). liver enzymes, and a creatinine level. Certain medications, including progestins, anabolic steroids, and corticosteroids, also can result in elevated cholesterol. Consideration should be given to changing or discontinuing these when possible.

Management

Therapeutic lifestyle changes (TLCs) are the cornerstone of all treatments for hyperlipidemia. All patients should be educated on healthier living, including dietary modifications, increased physical activity, and smoking cessation. Weight reduction should be encouraged.

Specific dietary recommendations should include a reduction of saturated fats to less than 7% of total calories and an intake of less than 200 mg/d of cholesterol. Total dietary fat should be kept to no more than 35% of total calories, with less than 10% polyunsaturated fat. Trans fats should be kept as low as possible.

When dietary restriction alone does not lead to adequate LDL reduction, the addition of dietary soluble fiber and plant stanols/sterols can be beneficial. Soluble fiber 10-25 g and of plant stanols/sterols 2 g can be added to aid in cholesterol reduction. Referral to a dietician may be helpful as well.

When TLC is instituted, regular follow-up must be arranged. Fasting lipids should be rechecked in approximately 6 weeks. If adequate reduction has occurred, reinforcement of the lifestyle changes should be given and the patient followed every 4—6 months.

Pharmacotherapy may be considered in patients who do not reach their LDL goals with TLC alone. TLC should continue to be reinforced and encouraged even when starting medications. In someone who does not have CHD or a risk equivalent (primary prevention), medications should be considered after the third visit of TLC management. In someone with CHD or an equivalent (secondary prevention), the more stringent LDL goals often require earlier institution of drug treatment.

The first-line pharmacotherapy for LDL cholesterol reduction is a statin. Statins not only reduce LDL cholesterol but also reduce the rates of coronary events, strokes, cardiac death, and all-cause mortality. When statin therapy is started, fasting lipids should be rechecked in 6 weeks. If LDL goals are not met, the dose of the statin can be increased or a second agent added. These other medications include fibric acids, nicotinic acids, bile acid seques-trants. and cholesterol absorption blockers (Table 35-3). When taking statins, liver enzymes must be monitored as well (6-12 weeks after initiation or dosage change, then every 6-12 months). When goal levels are met, regular follow-up should be arranged to reinforce lifestyle changes, medication compliance, and overall risk factor reduction.

Table 35-3

MEDICATIONS USED TO LOWER CHOLESTEROL

Table 35-3

MEDICATIONS USED TO LOWER CHOLESTEROL

DRUG

CLASS/

SIDE

MEDICATION

EFFECTS

EFFECTS

CONTRAINDICATIONS

Statin

LDL i

Myopathy.

Active or chronic liver

Lovastatin

18-55%:

myalgia.

disease: relative

Pravastatin

HDL t

increased

contraindication with

Fluvastatin

5-15%:

liver enzymes

cytochrome P450 inhibitors,

Atorvastatin

Iriglytrides

cyclosporine. macrolides.

Cerivastatin

(TG)i

antifungals

Simvastatin

7-30%

Bile acid

LDL i

GI distress.

Dysbetalipoproteinemia;

séquestrants

15-30%;

constipation.

TG >400

Cholestyramine

HDLt

decreased

Colestipol

3-5%;

absorption of

Colesevelam

TG no

other mes

change; or

increase

Nicotinic acids

LDL i

Flushing.

Absolute: chronic liver

Immediate-release,

5-25%;

hyperglycemia,

disease, severe gout;

sustained-release.

HDLt

hyperuricemia.

relative: diabetes.

or extended-

15-35%;

upper GI

hyperuricemia.

release nicotinic

TG i

distress.

peptic ulcer

acid

20-50%

hepatotoxicity

disease

Fibric acids

LDL 1

Dyspepsia,

Severe renal disease.

Gemfibrozil

5-20%;

gallstones.

severe hepatic disease

Fenofibrate

HDLT

myopathy.

Clofibrate

10-20%:

unexplained

TG i

non-CHD

20-50%

deaths in

WHO study

Cholesterol

LDL i

Abdominal pain.

Hepatic

absorption blocker

13-25%;

diarrhea

insufficiency/active

Ezetimibe

HDLt

liver disease

3-5%;

TG i

5-14%

Information from ATP III report and c/.elimibe product information.

Information from ATP III report and c/.elimibe product information.

Comprehension Questions

[35.1] A 62-year-old male smoker with no known history of CHD presents for follow-up of intermittent claudication. He has normal blood pressure and no family history of premature CHD. His HDL cholesterol is 48 mg/dL. According to the ATP III guidelines, what is his goal LDL?

[35.2] A 55-year-old woman presents to your office for follow-up. She was discharged from the hospital I week ago following a heart attack. She has quit smoking since then and vows to stay off cigarettes forever. Her lipid levels are total cholesterol 240: HDL 50 mg/dL; LDL 150 mg/dL: triglycerides 50 mg/dL. What is the most appropriate management at this time?

A. Institute therapeutic lifestyle changes alone

B. Institute TLC and a statin

C. Institute a statin alone

D. Institute TLC. a statin, and nicotinic acid

[35.3] A 48-year-old man with no significant medical history and no symptoms is found to have elevated cholesterol at a health screening. Which of the following tests is part of the routine evaluation of this problem?

B. Stress test

C. Complete blood count (CBC)

D. Thyroid-stimulating hormone (TSH)

Answers

B. This patient has symptomatic peripheral arterial disease, which is considered a CHD risk equivalent. His LDL goal is 100 mg/dL or less.

B. This patient has known CHD. documented by her recent myocardial infarction. Her goal LDL is 100 mg/dL or less. As her starting level is above 130 mg/dL. it would be reasonable to start both TLC and a statin to help her to reach her goal. Nicotinic acid may be a reasonable addition if the TLC and statin do not lead to adequate LDL reduction.

D. Hypothyroidism is a potential cause of secondary dyslipidemia. A TSH is a reasonable test to perform in this setting. There is no indication to screen for CHD with an EKG or stress test in this asymptomatic person. Other tests to perform could include a fasting sugar, liver enzymes, and a measurement of renal function.

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