Although it is possible to measure LDL-C directly, it is common for many laboratories to calculate LDL-C. Total cholesterol,

HDL-C, and TGs are measured directly and then the following

formula (Friedewald equation) is applied to calculate LDL-C:

LDL-C = Total Cholesterol − (HDL-C + VLDL-C) (Eq. 13-1)

268 Section 2 Cardiac and Vascular Disorders

TABLE 13-6

NCEP ATP III Classifications of Blood Lipids8

LDL-Cholesterol

<100 mg/dL Optimal

100–129 mg/dL Near optimal or above optimal

130–159 mg/dL Borderline high

160–189 mg/dL High

≥190 mg/dL Very high

Total Cholesterol

<200 mg/dL Desirable

200–239 mg/dL Borderline high

≥240 mg/dL High

HDL-Cholesterol

<40 mg/dL Low

≥60 mg/dL High

Triglycerides

<150 mg/dL Normal

150–199 mg/dL Borderline high

200–499 mg/dL High

>500 mg/dL Very high

HDL, high-density lipoprotein; LDL, low-density lipoprotein; NCEP ATP III,

National Cholesterol Education Program Adult Treatment Panel III.

Because the ratio of cholesterol to TGs in VLDL is 1:5, VLDLC is estimated by dividing the total TG level by 5. Thus, the

formula is rewritten as:

LDL-C = Total Cholesterol − (HDL-C + TG/5) (Eq. 13-2)

Applying the formula to T.A.’s lipid profile, the calculated

LDL-C is 224 mg/dL.

LDL-C = Total Cholesterol − (HDL-C + TG/5)

= 290 − (55 + 55/5)

= 224 mg/dL (Eq. 13-3)

If the TG level is greater than 400 mg/dL, the formula for

estimating VLDL-C is not accurate and, therefore, LDL-C cannot

be calculated. An accurate LDL-C measurement also requires

that the patient fast for 10 to 12 hours. This provides sufficient

time for exogenous TGs, carried by chylomicrons, to be cleared

from the systemic circulation (provided the patient does not have

hyperchylomicronemia). Most laboratories can measure LDL-C

directly and should be asked to do so only when the TG is greater

than 400 mg/dL or the patient has not fasted.

Non–HDL-C is calculated by the following formula:

Non–HDL-C = Total Cholesterol − HDL-C (Eq. 13-4)

For T.A.:

Non-HDC-C = 290 mg/dL − 55 mg/dL

= 235 mg/dL (Eq. 13-5)

As mentioned previously, non–HDL-C can be calculated

regardless of whether a patient is fasting or not because VLDL-C

does not need to be estimated. This provides the clinician information of a patient’s CHD risk when LDL-C cannot reliably be

calculated.

Secondary Causes of High

Blood Cholesterol

CASE 13-1, QUESTION 2: Is there any evidence that T.A.’s

elevated LDL-C is secondary to other conditions or concurrent drug therapy?

As a routine, every new patient with hypercholesterolemia

should be evaluated for four things in the following order: (a)

secondary causes of the high cholesterol level, (b) familial disorders, (c) presence of CHD and CHD equivalents, and (d) CHD

risk factors.

Conditions that can produce lipid abnormalities (i.e., secondary causes) include diabetes mellitus, hypothyroidism,

nephrotic syndrome, and obstructive liver disease. Selected drugs

can also produce lipid abnormalities (Table 13-7). When one of

these secondary causes is identified, it should be managed first

(unless there is a compelling reason to use the medication implicated), as this may resolve or improve the lipid abnormality.

In T.A.’s case, no secondary causes are evident. Her blood

glucose level does not indicate the presence of diabetes; her TSH

level does not indicate hypothyroidism; her ALT and AST levels are within acceptable levels, suggesting normal liver function;

and her blood urea nitrogen, creatinine, and urinalysis are acceptable, signifying normal renal function. She is not taking any drugs

that could have contributed to her cholesterol elevation.

Familial Forms of Hypercholesterolemia

CASE 13-1, QUESTION 3: Could T.A. have an inherited form

of hyperlipidemia?

T.A.’s history is consistent with polygenic hypercholesterolemia, the form of hypercholesterolemia that affects 98%

of patients with hypercholesterolemia. As described previously,

polygenic hypercholesterolemia is suspected when the patient’s

LDL-C is 130 to 250 mg/dL and no evidence is seen of tendon

xanthomas (Table 13-2). A family history of CHD is present in

approximately 18% of these patients and is a strong finding in

T.A.’s case. Polygenic hypercholesterolemia is caused by a combination of nutritional and genetic factors that reduce the clearance of LDL particles from the plasma. It is impossible to determine which of these factors are causing hypercholesterolemia

in a given patient by simply examining the lipoprotein profile.

If the patient’s blood lipids normalize with a low-fat diet, however, one can assume that the diet is a major etiologic factor for

that person. Conversely, if little or no change is seen in blood

cholesterol levels after dietary modification, genetics likely significantly influences the patient’s elevated cholesterol. In most

cases, a relatively equal contribution is made by genetic factors

and environment on cholesterol elevations. When patients are

identified with severely elevated LDL-C such as T.A., systematic family screening of relatives should be conducted to identify

other individuals, including children, who might be affected and

at high risk of CHD.

Coronary Heart Disease and Coronary

Heart Disease Risk Equivalents

CASE 13-1, QUESTION 4: Does T.A. have evidence of CHD

or a CHD risk equivalent?

A search for CHD starts with a good medical history of symptomatic CAD, but is quickly followed with a broader search for

atherosclerotic disease in other artery beds, including the arteries

of the limbs and carotid arteries8 (Table 13-8). If detected in one

site, atherosclerosis is likely to be present in all or most vessels,

and it is associated with a fivefold to sevenfold higher risk of a

major coronary event.142–144

The patient should be asked about a history of myocardial

ischemia (exercise-induced angina), prior MI (i.e., severe angina

269Dyslipidemias, Atherosclerosis, and Coronary Heart Disease Chapter 13

TABLE 13-7

Drug-Induced Hyperlipidemia

Effect on Plasma Lipids

Cholesterol (%) Triglycerides (%) HDL-C (%) Comments

Diuretics

Thiazides ↑5–7 initially

↑0–3 later

↑30–50 ↑1 Effects transient; monitor for long-term

effects

Loop No change No change ↓ to 15

Indapamide No change No change No change

Metolazone No change No change No change

Potassium-sparing No change No change No change

β-Blockers

Nonselective No change ↑20—50 ↓10–15 Selective β-blockers have greater effects

than nonselective; β-blockers with ISA

or α-blocking effects are lipid neutral

Selective No change ↑15–30 ↓5–10

α -Blocking No change or ↓ No change No change

α -Agonists and Antagonists

(e.g., prazosin and clonidine)

↓0–10 ↓ 0–20 ↑0–15 In general, drugs that affect α-receptors

↓cholesterol and ↑HDL-C

ACE Inhibitors No change No change No change

Calcium-Channel Blockers No change No change No change

Oral contraceptives

α-Monophasics ↑5–20 ↑10–45 ↑15 to ↓15 Effects caused by reduced lipolytic activity

or ↑VLDL synthesis; mainly caused by

progestin component; estrogen alone

protective

α-Triphasics ↑10–15 ↑10–15 ↑5–10

Glucocorticoids ↑5–10 ↑15–20

Ethanol No change ↑up to 50 ↑ Marked elevations can occur in patients

who are hypertriglyceridemic

Isotretinoin ↑5–20 ↑50–60 ↓10–15 Changes may reverse 8 weeks after

stopping drug

Cyclosporine ↑15–20 No change No change

ACE, angiotensin-converting enzyme; HDL-C, high-density lipoprotein cholesterol; ISA, intrinsic sympathomimetic activity; VLDL, very-low-density lipoprotein.

with elevated cardiac creatine phosphokinase [CPK] or characteristic ECG changes), history of revascularizations (i.e., coronary

artery bypass surgery, angioplasty with percutaneous transluminal coronary angioplasty or stent placement), or history of

TABLE 13-8

NCEP APT III Definitions of CHD and CHD Risk Equivalentsa,8

Clinical CHD

Myocardial ischemia (angina)

Myocardial infarction

Coronary angioplasty and/or stent placement

Coronary bypass graft

Prior unstable angina

Carotid Artery Disease

Stroke history

Transient ischemic attack history

Carotid stenosis >50%

Peripheral Arterial Disease

Claudication

ABI >0.9

Abdominal Aortic Aneurysm

Diabetes Mellitus

a Estimated global CHD risk >20% in 10 years for any of the factors listed.

ABI, ankle-to-brachial blood pressure index; CHD, coronary heart disease; NCEP

ATP III, National Cholesterol Education Program Adult Treatment Panel III.

hospitalization because of unstable angina (see Table 13-8). The

presence of any of these findings is associated with a very high

(>20%) risk of a CHD death or nonfatal MI in the next 10 years;

the risk approaches 40% if unstable angina and stroke are also

considered. None of these signs are present in T.A.

The evaluation can stop here, but some would advocate

continuing the search with noninvasive procedures, even if the

patient has not experienced symptoms (Table 13-9). The case for

pursuing these evaluations is more convincing in patients who

have a high probability of atherosclerosis because of the presence of multiple risk factors or a strong family history of premature CHD events. One noninvasive evaluation is exercise testing

with either ECG monitoring for signs of ischemia or pharmacologic perfusion imaging (e.g., exercise thallium). Because these

tests are expensive and not widely available, they are reserved

for selected use. Even if the results are found to be normal,

atherosclerosis is not ruled out because both tests are designed

to detect flow-limiting disease, and atherosclerosis can be present

without causing obstructions in luminal blood flow.8

In recent years, electron beam computed tomography and spiral computed tomography have been used to detect calcium in

coronary vessels. The presence of coronary calcium suggests the

presence of old atherosclerotic plaque. If old disease is present,

then it is likely that younger, more vulnerable plaques are also

present. This test is simple, quick, and noninvasive, but it is

relatively expensive, not widely available, and not typically covered by insurance plans. High coronary calcium volume scores

270 Section 2 Cardiac and Vascular Disorders

TABLE 13-9

Emerging CHD Risk Factors8

Noninvasive Evaluations for

Subclinical Atherosclerosis Blood Tests

Exercise ECG Lipoprotein(a)

Myocardial perfusion imaging Small, dense LDL

Stress echocardiography Apolipoprotein B (particle

concentration)

Carotid intimal-medial thickness

(IMT)

High-sensitivity CRP (and other

inflammatory markers)

Electron beam computed

tomography (EBCT)

Homocysteine

HDL subspecies

Apolipoprotein A-I

Apolipoprotein B:C-III

Thrombogenic factors (e.g.,

fibrinogen, PAI-1, t-PA)

LP-PLA2

CHD, coronary heart disease; CRP, C-reactive protein; ECG, electrocardiogram;

HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein;

LP-PLA2, lipoprotein associated phospholipase A2; PAI, plasminogen activator

inhibitor; t-PA, tissue plasminogen activator.

can add to the prediction of future coronary events based on traditional risk factor assessment.8 Use of these tests is particularly

helpful in modifying the assessment of risk in patients with multiple risk factors. In T.A.’s case, her strong family history could

support obtaining an electron beam computed tomography evaluation. If she has a significantly positive calcium volume score,

more aggressive medical therapy could be considered.

A good history should also probe for evidence of atherosclerotic vascular disease in peripheral vessels. Patients with flowlimiting atherosclerosis in peripheral vessels often describe claudication (pain and weakness in the limb muscles) after walking a

distance (see Chapter 15, Peripheral Vascular Disorders). NCEP

recommends that patients older than 50 years of age be evaluated

with an ankle-to-brachial index (ABI). This index is determined

by measuring the systolic blood pressure of the brachial, posterior tibia, and dorsalis pedis arteries using a handheld Doppler

device and dividing the higher of the two ankle systolic blood

pressures by the higher of two systolic brachial pressures.8 An

ABI of less than 0.9 constitutes the diagnosis of peripheral vascular disease (PVD; also called peripheral arterial disease). Finding

atherosclerosis in peripheral vessels probably means it is present

in coronary arteries as well. In fact, most patients with PVD die

of a CHD event. Furthermore, most patients with PVD have a

very high (>20%) risk of a CHD event in the next 10 years, and

so are said to have a CHD risk equivalent.

The clinician should also evaluate the patient for atherosclerosis in the carotid vessels by asking about signs and symptoms

of transient ischemic attacks and strokes. On the physical examination, the carotid vessels should be evaluated for the presence of

a bruit (indicative of a space-occupying lesion in the carotid vessel). If a bruit is present, further evaluation with carotid duplex

imaging is indicated to detect stenotic lesions. Some authorities recommend performing carotid sonography to measure the

carotid intimal-medial thickness (CIMT). This test is safe and

simple but relatively expensive and not widely available. Intimalmedial thickness results correlate with the severity of coronary

atherosclerosis. Patients who have experienced a stroke or transient ischemic attack have a more than 20% 10-year risk of experiencing a CHD event and so are also considered a CHD risk

equivalent. Patients found to have a stenosis of greater than 50%

in their carotid vessel, even if asymptomatic, have a more than

20% 10-year CHD risk and again can be considered a CHD risk

equivalent. Patients found to have an increased intimal-medial

thickness, suggesting the presence of subclinical atherosclerosis,

may also have a high CHD risk and, therefore, are candidates for

more aggressive medical therapy.8

Other conditions that confer a greater than 20% risk of a CHD

event in the next 10 years, and thus are considered by NCEP to

be CHD risk equivalents, include abdominal aortic aneurysm

and the diagnosis of diabetes. More will be said about diabetes

subsequently. T.A. does not have evidence of CHD or a CHD risk

equivalent.

CORONARY HEART DISEASE RISK FACTORS

CASE 13-1, QUESTION 5: Does T.A. have CHD risk factors,

and what is her global CHD risk?

Patients who are found to have CHD or CHD risk equivalent

do not need a risk factor assessment to establish their LDL-C

treatment goal; the presence of CHD or a CHD risk equivalent

satisfies that. These patients, however, should have an appraisal

of risk factors so that risk-factor modification can be incorporated

in the overall treatment plan. For patients who do not have CHD

or a CHD risk equivalent, risk-factor counting and global risk

assessment is important to quantify baseline risk and to establish

initial treatment goals and approaches.

Begin this process by counting the number of risk factors

present (Table 13-4). Patients with either zero or one risk factor most likely have a low risk of a CHD event in the next 10

years and are assigned an LDL-C goal of less than 160 mg/dL.

Patients with two or more risk factors have a moderate to high

risk, depending on the number and type of risk factors present.

NCEP recommends that patients who have two or more risk factors be further evaluated using the Framingham-based global

risk assessment tool (http://hp2010.nhlbihin.net/atpiii/

calculator.asp?usertype=prof ) to define the 10-year risk.

Patients with two or more risk factors have an LDL-C goal of at

least less than 130 mg/dL. The clinician, however, has the option

to treat these patients to reach less than 100 mg/dL depending

on clinical judgment of the patient’s absolute risk and potential

benefit if that patient’s Framingham calculated 10-year CHD risk

is between 10% and 20%. If the patient’s calculated risk is more

than 20%, their risk is equivalent to someone with CHD and

their LDL-C goal is less than 100 mg/dL. The presence of modifiable risk factors should become the target of any risk-reduction

treatment program. It is important to note that the Framingham

risk score is recommended to patient-specific baseline risk of a

CHD event and baseline LDL-C goals. Although it is tempting to

recalculate risk in primary prevention patients once risk factors

have been modified, it is not the intent to use the Framingham

risk score to guide therapy in a primary prevention patient with

multiple major CV risk factors.

T.A. has two CHD risk factors: current cigarette smoking

and a family history of premature CHD. She thus has an LDL-C

treatment goal of less than 130 mg/dL (Table 13-10). T.A. is found

to have a 5% 10-year CHD risk, which is several times greater

than the average risk for women her age but below the threshold

at which aggressive drug treatment is indicated (i.e., >10% CHD

risk in 10 years). If she were not a smoker, her 10-year CHD risk

estimate would be 1%, illustrating the prominent influence that

smoking has on her future risk of a CHD event.

Based on this assessment and assuming that the noninvasive

assessments performed on her, if any, were negative, T.A. should

be counseled on diet and exercise and strongly advised to stop

smoking. Because of its strong effect on her risk, smoking cessation (see Chapter 88, Tobacco Use and Dependence) should be a

primary focus of her risk-reduction program. If these measures

271Dyslipidemias, Atherosclerosis, and Coronary Heart Disease Chapter 13

TABLE 13-10

NCEP ATP III and AHA/ACC LDL-C Goals and Cut Points for Therapeutic Lifestyle Changes (TLC) and Drug Therapy8,107,108

Risk Category LDL-C Goal

LDL-C at Which

to Initiate TLC LDL-C at Which to Consider Drug Therapya

CHD or CHD risk equivalents

(10-year risk >20%)

<100 mg/dL

(Optional goal <70 mg/dL)c

>100 mg/dL >100 mg/dL (<100 mg/dL; consider drug

options)b

2+ risk factors (10-year risk 10%

to 20%)

<130 mg/dL

(Optional goal <100 mg/dL)

>130 mg/dL >130 mg/dL (100–129 mg/dL; consider drug

options)d

2+ risk factors (10-year risk <10%) <130 mg/dL >130 mg/dL >160 mg/dL

<2 risk factorse <160 mg/dL >160 mg/dL 190 mg/dL (160–189 mg/dL; LDL-C–lowering

drug therapy is optional)

a For all patients without CHD: LDL-C–lowering medications should be initiated at a dose that is consistent with at least a 30% to 40% reduction in LDL-C levels. The use of

lower doses just to barely attain the LDL-C goal would not be a prudent use of medications.

bThe clinician may select niacin or fibrate therapy if patient has high triglycerides or low HDL-C. The decision to lower LDL-C with drug therapy is optional based on

available clinical trial evidence.

cAll patients with CHD: When LDL-C <70 mg/dL is not achievable because of high baseline LDL-C levels, it generally is possible to achieve reductions of >50% by either

statins or LDL-C–lowering drug combinations.

dThe decision to lower LDL-C with drug therapy to achieve an LDL-C <100 mg/dL is optional based on available clinical trial evidence. e Patients with fewer than two risk factors usually have a 10-year risk of <10%, and therefore do not need a 10-year risk assessment.

AHA/ACC, American Heart Association/American College of Cardiology; CHD, coronary heart disease; LDL-C, low-density lipoprotein cholesterol; NCEP ATP III,

National Cholesterol Education Program Adult Treatment Panel III.

fail to bring her LDL-C to her treatment goal of less than 130

mg/dL and her LDL-C remains 160 mg/dL or more, drug therapy

should be considered (Table 13-10). If she stopped smoking, however, she would have only one risk factor (family history), and

her new LDL-C goal would be less than 160 mg/dL. In this case,

drug therapy would be considered only if the LDL-C remains

190 mg/dL or more.

Therapy for Lowering Cholesterol Levels

DIET THERAPY

CASE 13-1, QUESTION 6: What lifestyle changes should be

recommended to T.A.?

The centerpiece of treatment for high blood cholesterol is

a diet low in saturated fat and cholesterol. The TLC diet recommended by NCEP restricts total fat intake to 25% to 35%

of calories, saturated fats to less than 7% of calories, and dietary

cholesterol to 200 mg/day (Table 13-11).8 The TLC diet is aggressive and requires instruction by a dietitian, nurse, or other health

professional well versed in nutrition counseling. The TLC diet

is also flexible and allows for modification of carbohydrate and

monounsaturated fat intake according to the individual patient’s

needs. The goals presented by the TLC diet are minimal goals,

and some patients will want to exceed them, even to the point

of following a vegetarian diet. This is permissible, as long as the

diet is nutritionally balanced.

TABLE 13-11

NCEP ATP III Therapeutic Lifestyle Change Diet8

Nutrient Recommended Intake

Total fat 25%–35% of total calories

Saturated fat <7% of total calories

Polyunsaturated fat Up to 10% of total calories

Monounsaturated fat Up to 20% of total calories

Carbohydrate 50%–60% of total calories

Fiber 20–30 g/day

Cholesterol <200 mg/d

Protein Approx. 15% of total calories

When saturated fat is removed from the diet, it is important

to understand what should be given in replacement. In the overweight or obese patient, it may be appropriate to do nothing,

because a reduction in saturated fat is a good way to lower calories and encourage weight loss.

In individuals who are close to their ideal weight, such as

T.A., replacing saturated fats with carbohydrates may not be

the best choice. Increased intake of sugar and highly refined

starches, as found in the many low-fat, high-calorie snack foods,

may actually increase weight and reduce HDL-C as well as

LDL-C.145 More importantly, a low-fat, high-carbohydrate diet

has not been shown to reduce the risk of CHD. Consumption of

complex carbohydrates is recommended, however, and could be

a replacement for saturated fat calories in a TLC diet.

Replacing saturated fat with unsaturated fats, especially

monounsaturated fats (e.g., canola oil or olive oil products) and

omega-3 polyunsaturated fats (e.g., fish oil sources), is highly

desirable.146 This is the diet of the Mediterranean people, who

have a low incidence of CHD, and has the advantage of lowering

LDL-C without affecting HDL-C. In fact, in a major randomized clinical trial in which the Mediterranean diet was compared

with a “prudent Western-type diet,” the Mediterranean diet was

associated with a greater than 70% reduction in cardiovascular

end points and total mortality, a result that exceeds that achieved

by the best lipid-lowering drug trials.147 This study alone illustrates how important it is to initiate a good diet in hyperlipidemic

patients, even with the availability of very potent, highly efficacious, and safe drugs to lower serum cholesterol levels.

In Western society, diets high in protein and saturated fats and

low in carbohydrates (e.g., Atkins diet) promise quick weight loss

and other health effects. Although these diets can reduce lipid

levels and cause weight loss, they are not nutritionally sound and

may even be unhealthy. Patients should be advised to avoid them.

T.A. is likely to need help in translating the dietary recommendations of a TLC diet into practical terms and concepts that

she can easily implement in her everyday life. Two approaches

can be used to achieve this: (a) teach her to count calories or (b)

provide general guidance in the selection of low-fat foods.

The more sophisticated patient may want to count calories

or grams of total and saturated fat per day. The first step in

teaching a patient to do this is to determine his or her daily caloric

requirements, adjusted for his or her level of activity. The average

caloric requirement for women is 1,800 calories/day; for men it

272 Section 2 Cardiac and Vascular Disorders

is 2,500 calories/day. Based on this, T.A. should be instructed to

keep her total fat intake to 450 to 630 calories/day (25% to 35%

of calories) and saturated fat to less than 126 calories/day (<7%

of total calories). Converting fat calories to grams (i.e., dividing

calories by 9 cal/g), T.A. should be instructed to restrict her total

fat intake to less than 50 to 70 g/day and saturated fat to less than

14 g/day.

Once these calculations have been made, the next step is

to teach T.A. how to determine the grams of saturated and

unsaturated fat contained in the foods she eats by reading food

labels and referring to reference charts or books that list the

nutritional content of foods. A good source for this nutrition

information is the National Institutes of Health website on Therapeutic Lifestyle Change (http://www.nhlbi.nih.gov/health/

public/heart/index.htm) under the Health Information icon.

This site contains information on the TLC diet, a 10-year risk

calculator, recipes, a virtual grocery store, a cyberkitchen, a fitness room, and a resource library. The AHA sites (http://www.

heart.org/HEARTORG/GettingHealthy/GettingHealthy

UCM 001078 SubHomePage.jsp and http://www.delicious

decisions.org) provide equally good information on risk

assessment, a cholesterol tracker, low-fat recipes, and guidance

for eating in restaurants, cooking, and fitness.

For patients who are not able or willing to count calories

or grams, general instruction on how to select low-fat foods

and control portion sizes of higher-fat foods would provide an

alternative approach. Principles to teach include the following:

 Eat less high-fat food (especially food high in saturated fats).

 Replace saturated fats with polyunsaturated and monounsaturated fats and fish oils whenever possible.

 Eat less high-cholesterol food.

 Choose foods high in complex carbohydrates (starch and

fiber).

 Attain and maintain an acceptable weight.

T.A. should be counseled to recognize and minimize the three

main sources of saturated fats in her diet: meat products, dairy

products, and oils used in processed foods and cooking.

All meat products, including beef, pork, and poultry, contain

fat. Much of the fat is visible and should be trimmed off before

consumption. The remaining fat is contained within the meat

and can be limited by (a) selecting the leanest meat (e.g., lean

beef, skinless chicken, fish), (b) limiting portion size to about the

size of a deck of playing cards (no more than 6 ounces/day), and

(c) cooking the meat in a manner that allows the fat to drip away

from the meat (i.e., broiling, grilling).

High-fat dairy products are made with whole milk (∼4% fat);

low-fat alternatives are made with skim or 1% milk (which contain all of the nutrient value of whole-milk products). T.A. should

be taught to substitute low-fat alternatives for high-fat products—

for example, by choosing soft margarine (or no fatty spread at

all) instead of stick butter (note that unsaturated fats exist normally in liquid form and saturated fats in solid form); nonfat

creams rather than whole-milk creams; low-fat or nonfat soft

cheese (e.g., cottage cheese) rather than natural or processed

hard cheese (including cream cheese); skim milk rather than

whole milk; light or nonfat sour cream rather than regular sour

cream; and nonfat frozen yogurt rather than ice cream. She also

should avoid or limit cream sauces on meats and vegetables and

creamy soups.

Products prepared with coconut, palm, or palm kernel oils,

as well as lard and bacon fat, contain a high concentration of

saturated fats, and intake should be restricted. In their place,

products made with monounsaturated fats (e.g., olive oil, canola

oil) or polyunsaturated fats (especially oils that contain omega3 fatty acids) may be substituted. Monounsaturated fats have

little or no effect on blood lipids, and polyunsaturated fats actually may help reduce total cholesterol. Also, when the “good”

(unsaturated) oils are partially hydrogenated (i.e., saturated to

make them solid, as in some margarine products), they take on

the character of saturated oils and may raise cholesterol levels.

These are called trans fatty acids. Major sources of saturated and

trans fatty acids include cakes, pies, cookies, chips, and crackers.

T.A. should be advised to avoid or limit not only saturated fats,

but also trans fatty acids by reading food labels.

It is best not to give the patient a list of foods to avoid; this

aversive approach is likely to fail. Rather, good instruction about

a low-fat diet should teach the patient how to make good selections. Any food, even a high-fat food, is not prohibited as long as

portion size and frequency of use are controlled.

Another dietary approach to lowering blood cholesterol is to

use dietary adjuncts. For example, adding 5 to 10 g of viscous fiber

(e.g., guar, pectin, oat gum, psyllium) or other dietary sources

of fiber (e.g., vegetables, legumes, whole grains, fruits) to the

diet daily will aid in lowering blood cholesterol levels about 5%

on average. Also, plant stanol and sterol esters have been made

available in margarine and salad dressing products and can lower

LDL-C 5% to 15% when the equivalent of one tablespoonful

is ingested one to three times a day. They act by reducing the

absorption of cholesterol in the intestine. The estimated cumulative percent reduction in LDL-C achievable through TLC is

between 20% and 30%.

T.A. will need to follow a low-fat diet indefinitely to sustain its

benefit. For this reason, it might be necessary to have T.A. work

with a registered dietitian or other professional who understands

low-fat, low-cholesterol diets and who can give her personalized

instruction. Particularly important is instruction on how to shop

for and prepare low-fat foods and how to select low-fat foods in

restaurants.

EFFECT ON LOW-DENSITY LIPOPROTEIN CHOLESTEROL

CASE 13-1, QUESTION 7: What changes in T.A.’s LDL-C can

be expected if she follows a TLC diet?

LDL-C is reported to be reduced by an average of 3% to

14% in men who restrict saturated fat to less than 10% of calories; a slightly smaller response is attained in women, perhaps

because their intake of saturated fats is generally lower than that

of men.148–150 Patients who can restrict saturated fat intake to

less than 7% of daily calories should experience an additional

3% to 7% average reduction. Most patients can attain at least a

5% reduction in cholesterol levels with a TLC diet, some patients

much more. If dietary adjuncts are added, LDL-C may be lowered

by an additional 5% to 15%.

Patients’ response to a low-fat diet is variable. In some patients,

blood cholesterol levels fall substantially, whereas in others practically no change occurs. Response to a low-fat diet depends on

many factors, including the patient’s dietary habits before implementing the low-fat diet, the patient’s adherence with the diet,

the degree to which the patient restricts fats and cholesterol, and

the influence of genetic factors. The patient should not be discouraged if LDL-C levels do not change much or at all despite

close adherence to the diet. The Mediterranean diet, for example,

which is high in monounsaturated fats and fiber, has no appreciable effect on blood lipids, but can still reduce cardiovascular

disease and mortality by 70%.147 Patients who adhere to a low-fat

diet might also respond to lower doses of lipid-lowering drugs.

Because T.A. is a woman and was following a low-fat diet

before her diagnosis, a TLC diet is not likely to have a substantial

effect on her blood cholesterol levels. It would be prudent to have

her maintain a 3-day diary of everything she eats to allow a more