1. Evolution of NCEP guidelines: ATPI - ATP III
Content Points:
The Third Report of the NCEP Adult Treatment Panel III (ATP III) offers updated cholesterol management guidelines for primary and secondary prevention of coronary heart disease (CHD). This slide highlights steps in the evolution of the guidelines.
ATP I, published in 1988, focused on primary prevention and identified low-density lipoprotein-cholesterol (LDL-C) as the main target of therapy. ATP I emphasized treatment of higher LDL-C levels to achieve the goal of LDL-C <130 mg/dL.
ATP II, published in 1993, affirmed LDL-C as the main therapeutic target. However, ATP III expands the indications for cholesterol-lowering in clinical practice. A new addition was more intensive management of LDL-C in patients with CHD to reach a target LDL-C goal of <100 mg/dL.
In ATP III, LDL-C remains the primary therapeutic target. The major new feature is a focus on primary prevention in persons with multiple risk factors. Many of these individuals have a relatively high risk for CHD and will benefit from more intensive LDL-C lowering.
ATP III introduces the concept of the CHD risk equivalent. It refers to conditions that confer the same short-term (10-year) risk as CHD for a major coronary event (myocardial infarction or coronary death).
Diabetes is identified as a CHD risk equivalent (rather than a risk factor as in ATP II). A second new potential risk equivalent is a subgroup of patients with multiple (2+) risk factors, depending on the degree of risk. People with multiple metabolic risk factors (the metabolic syndrome) are singled out for intensive lifestyle therapies.
A major modification in lipid classification in ATP III is the identification of LDL-C <100 mg/dL as optimal. Low high-density lipoprotein cholesterol (HDL-C) is raised from <35 mg/dL to <40 mg/dL. Greater emphasis is also placed on treatment of lower triglyceride levels.
ATP III recommends in-hospital assessment of LDL-C for patients with CHD-related events (MI, unstable angina, revascularization) and that LDL-C-lowering therapy be prescribed when patients are discharged from the hospital.
ATP III recommends a complete lipoprotein profile (total cholesterol, LDL-C, HDL-C, and triglycerides) as the preferred initial test.

2. ATP III: Cholesterol classification (mg/dL)
Content Points:
ATP III continues to focus on reduction of elevated LDL-C as the primary target of therapy. The emphasis is based on multiple avenues of research indicating that elevated LDL-C is a major cause of CHD. In addition, recent clinical trials show that LDL-C-lowering therapy reduces CHD risk. Therefore the primary cutpoints of therapy are stated in terms of LDL-C.
The new guidelines include changes in LDL-C classification to reflect clinical study data showing that the relationship between LDL-C and CHD risk is continuous over a broad range of LDL-C levels, from low to high.
ATP III identifies LDL-C <100 mg/dL as optimal, because the risk of developing a CHD event appears to be reduced at this level. In ATP II, the optimal level was <130 mg/dL.
ATP III defines high-risk LDL-C as mg/dL and includes an additional category of >190 mg/dL as very high. In ATP II, high-risk LDL-C was defined only as >160 mg/dL.
ATP III total cholesterol values are unchanged from ATP II.
ATP III has redefined low HDL-C as <40 mg/dL rather than <35 mg/dL. Low HDL-C is an independent predictor of CHD events.
Lipoprotein levels should be determined by obtaining a complete lipoprotein profile with total cholesterol, LDL-C, HDL-C, and triglycerides after a 9-12 hour fast. If a nonfasting analysis is done, only total cholesterol and HDL-C levels provide reliable estimates.

3. ATP III: High-risk candidates for intensive treatment
Content Points:
A basic principle of prevention in the new guidelines is that the intensity of risk-reduction therapy should be adjusted to a person’s absolute risk of a major event (MI or cardiovascular death). Hence, the first step in evaluating the patient for treatment is to assess the patient’s risk status.
The patients at highest risk are those with CHD and CHD risk equivalents. CHD risk equivalents carry a risk for major coronary events equal to that of established disease.
Diabetes is identified as a CHD risk equivalent (rather than as a risk factor as in the past) because it confers a high risk of new CHD within 10 years, in part because it is frequently associated with multiple risk factors. Also, persons with diabetes who have an MI have an unusually high death rate, either immediately or long-term, and a more intensive preventive strategy is therefore warranted.
Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) are CHD risk equivalents.
Certain patients who have multiple (2+) risk factors are classified as having a CHD risk equivalent because of the number and severity of their risk factors.
Patients with multiple metabolic risk factors (metabolic syndrome) are candidates for more intensive therapy.

4. ATP III: Major risk factors that modify LDL-C goals
Content Points:
For patients who do not have CHD or a CHD risk equivalent, the presence of major risk factors (in addition to patient’s LDL-C level) should be determined to identify patients at high risk who require more intensive treatment. These risk factors include the following:
– Age: >45 years in men and >55 years in women – Cigarette smoking status – Hypertension: blood pressure >140/90 mm Hg or currently on    antihypertensive medication – Low HDL-C: <40 mg/dL; HDL-C >60 mg/dL is counted as a    negative risk factor, ie, 1 risk factor is subtracted from the total    count if it is present – Family history of premature CHD: CHD in first-degree male    relatives aged <55 years and in first-degree female relatives    aged <65 years
Persons who have multiple (2+) risk factors are classified as high-risk patients. They are further stratified according to the extent of their risk factors to determine how intensively they should be treated by calculating Framingham risk points. This risk assessment tool derived from Framingham Heart Study data is included in the guidelines. The process is described in the following slides.

5. NCEP/Framingham estimate of 10-year CHD risk in men without CHD
Content Points:
Framingham point score assessments of 10-year CHD risk are intended for persons with multiple (2+) risk factors who do not have heart disease or a CHD risk equivalent. Risk estimates are based on the number and severity of cardiovascular risk factors. The slide shows the points in each risk category for men. Estimates of 10-year CHD risk (%) form the basis for treatment decisions. The scoring should not be used in place of a medical examination.
Risk is calculated separately for men and women based on age, total cholesterol (vs age), HDL-C, systolic blood pressure, and cigarette smoking status (vs age).
Increasing levels of total cholesterol add substantially to risk, as indicated by the point scores in each age category. The new cutpoint for low HDL-C is <40 mg/dL. Of note, the LDL-C level is not a component of risk score estimates simply because the Framingham database has far more information on total cholesterol and HDL-C.
Systolic blood pressure has been identified as a more accurate predictor of CHD risk, particularly after age 50. Therefore, ATP III has removed diastolic blood pressure measurements from risk scoring. At any blood pressure level, patients who use blood-pressure–lowering medication are given more points because the presence of hypertension incurs some residual risk.
Cigarette smoking, especially at younger ages, is a potent risk factor for CHD, as demonstrated by the point scores from ages 20 through 49 years.
10-year risk is determined by totaling the points the patient receives in all five risk categories. The point total correlates with 10-year risk by percent, as shown at the bottom of the slide.

6. NCEP/Framingham estimate of 10-year CHD risk in women without CHD
Content Points:
The slide shows the Framingham points in each risk category for women. These scores are intended for women who do not have known heart disease or a CHD risk equivalent and they are not intended as a substitute for a medical examination.
Prior to age 40, women receive a lower negative number for age compared with men. After age 64, women receive more points for age than men.
For total cholesterol levels above 200 mg/dL, women in all age categories receive higher point scores than men.
Women receive more points than men for each systolic blood pressure level >120 mm Hg.
Up to the age of 70 years, women who smoke receive a higher number of points than men in similar age categories.

7. Framingham point total determines 10-year CHD risk Content Points:
The 10-year risk for a hard CHD event is determined by adding up the points for each of the five risk factors:
Points for Age + Total *cholesterol + HDL-C + Smoking status + Systolic BP = Point total
The 10-year absolute risk for a hard CHD event is determined from the point total according to sex. The point system differs significantly for men and women because in general, men have a higher CHD risk than do women, particularly in middle age.
For example, a point total of 15 for a woman is associated with a 3% absolute risk, whereas for a man it is associated with a 20% absolute risk.

8. Framingham men: Excess risk of total cholesterol
Content Points:
Framingham data show that incremental increases in total cholesterol augment the 10-year risk for CHD in every age category. Conversely, lowering total cholesterol level reduces CHD risk.
This slide shows the Framingham risk points that the age risk factor confers on men, which increase with advancing age. The excess risk burden in men imposed by increasing total cholesterol levels at every age range is also shown.
An example of the ability to reduce risk by lipid lowering is shown in a 55-year-old man (inset). A 55-year-old man receives 8 points for his age. His total cholesterol level of 300 mg/dL adds 5 points, for a subtotal of 13 points. These two risk factors alone place his 10-year risk at 12%, before any of the other risk factors are considered (ie, smoking status, systolic blood pressure, and HDL-C).
A reduction in total cholesterol to 155 mg/dL lowers this 55-year-old man’s point subtotal to 8, as a total cholesterol level of 160 mg/dL or less receives zero points. Thus, lipid-lowering alone reduces his 10-year CHD risk to 4% (or by 66%).

9. Framingham women: Excess risk of total cholesterol
Content Points:
Shown are the increasing Framingham risk points for women with advancing age. Shown also is the excess risk burden that women incur with increasing levels of total cholesterol at every age range.
Women are assigned a higher point score in every age range when their total cholesterol levels are >200 mg/dL. Cholesterol lowering strategies are similar for women and men for primary and secondary prevention.

10. ATP III: Risk categories and LDL-C goals
Content Points:
ATP III identifies three categories of risk for having a major CHD event within 10 years: >20%, <20%, and <10%. These categories determine both the target LDL-C and the timing of management strategies. Persons at highest risk receive the most intensive treatment.
CHD and CHD risk equivalents: The highest risk category includes patients with CHD or CHD risk equivalents (diabetes, other cardiovascular diseases, some persons with multiple risk factors, depending on the number and severity of their cardiovascular risk factors). Persons in the highest risk category have a >20% risk of CHD in 10 years. The target LDL-C is <100 mg/dL.
Multiple (2+) risk factors: Most persons with multiple (2+) risk factors have a CHD risk of <20%. The recommended target LDL-C is <130 mg/dL.
0-1 risk factors: Persons in this risk category with few exceptions have a 10-year CHD risk of <10%. In this category, the target LDL-C is <160 mg/dL.

11. ATP III: LDL-C cutpoints for treatment according to risk category
Content Points:
Multiple avenues of research indicate that elevated LDL-C is a major cause of CHD. Clinical trials show that LDL-C–lowering therapy reduces the risk for CHD. For these reasons, the primary goals of therapy and the cutpoints for initiating treatment are stated in terms of LDL-C.
ATP III defines cutpoints for initiating therapeutic lifestyle changes (TLC) and drug therapy according to category of risk.
CHD and CHD risk equivalents: In this highest risk category, the cutpoint for initiating TLC is LDL-C >100 mg/dL. The guidelines advise initiating drug therapy concurrently with TLC if baseline LDL-C is >130 mg/dL.
For LDL-C levels between mg/dL, the use of drug therapy relies on clinical judgment. Some authorities recommend use of LDL-C–lowering drugs if LDL-C is >100 mg/dL. Others prefer drugs that modify HDL-C or triglycerides (eg, nicotinic acid or fibrates).
Multiple (2+) risk factors and 10-year risk of 20% or less: For these patients, the goal of treatment is LDL-C <130 mg/dL. The cutpoint for initiating TLC is LDL-C >130 mg/dL. Two subcategories of risk determine when drug therapy should be considered:
– 10-year CHD risk of 10%-20%: the cutpoint for drug therapy is     LDL-C >130 mg/dL. Drug therapy should be introduced after 3     months of TLC as needed. – 10-year CHD risk <10%: Drug therapy should be introduced    after 3 months of TLC if LDL-C >160 mg/dL.
0-1 risk factor: Most persons with 0-1 risk factor have a 10-year CHD risk of <10%. In this risk category the target LDL-C is <160 mg/dL. If LDL-C is >160 mg/dL, first-line therapy is TLC.
Drug therapy should be considered for persons with 0 to 1 risk factor if their LDL-C is >190 mg/dL. For those whose LDL-C is mg/dL, drug therapy is an option based on clinical judgment. The presence of a severe single risk factor (cigarette smoking, severe hypertension, strong family history of premature CHD, or very low HDL-C) or a 10-year risk approaching 10% would favor the use of drugs to reach LDL-C <160 mg/dL.

12. Step care for achieving therapeutic lifestyle changes (TLC)
Content Points:
ATP III recommends multi-faceted therapeutic lifestyle changes, TLC, to reduce the risk for CHD for both primary and secondary prevention. The essential features of TLC strategies include dietary modifications that stress low saturated fats and cholesterol, weight reduction, and increased physical activity. The first therapeutic priority is to achieve the LDL-C target.
Six weeks after TLC is initiated, the LDL-C response should be determined. If the LDL-C goal is not achieved, additional therapeutic options to lower LDL-C include the use of plant stanols/sterols (2 g/day) and increased intake of fiber.
On the third patient visit, after 3 months of TLC, LDL-C should be evaluated. If it is not at the designated target, drug therapy can be considered.
After maximum reduction of LDL-C with dietary therapy/TLC, emphasis shifts to management of the metabolic syndrome. Weight reduction and physical activity should be intensified both to lower LDL-C and provide other health benefits.
Every 4 to 6 months, patients should be monitored to reinforce adherence to lifestyle therapies. Even if drug treatment is prescribed, attention to lifestyle therapies should be maintained.
Referral for medical nutrition therapy is encouraged at all stages of dietary therapy. Nutritional information and guidance can be provided by a registered dietician or other qualified nutritionist.

13. Progression of drug therapy in primary prevention
Content Points:
Many patients require LDL-C–lowering drugs in addition to TLC to reach the designated LDL-C target.
When drug therapy is considered, the third visit is usually when it is initiated. The first priority of drug therapy is to achieve the LDL-C goal. For this reason, an LDL-C–lowering drug should be started, usually a statin, given at a moderate dose. Most patients reach the LDL-C goal at this dose. Alternative LDL-C–lowering agents are a bile acid sequestrant or nicotinic acid.
The patient’s response is evaluated after about 6 weeks. If the goal is achieved, the current dose can be maintained. Otherwise, LDL-C–lowering therapy can be intensified by increasing the statin dose or by combining the statin with other agents.
After 12 weeks of drug therapy, the response should be assessed. If the LDL-C goal is not achieved, therapy can be intensified or referral to a lipid specialist may be considered.
Thereafter, patient can be monitored every 4 to 6 months or more often if necessary.
Once the LDL-C goal is reached, attention may turn to other lipid risk factors. However, lowering LDL-C often has a favorable affect on HDL-C and triglyceride levels.

14. Drug therapy for patients with CHD and CHD risk equivalents
Content Points:
For patients with CHD or a CHD risk equivalent, the treatment goal is LDL-C <100 mg/dL. Most patients need LDL-C–lowering drug therapy to achieve this target in addition to lifestyle therapies, such as dietary modification and exercise.
Consider initiating drug therapy simultaneously with lifestyle changes in patients with CHD and CHD equivalents who are not at LDL-C <100 mg/dL.
Other lipid risk factors may also warrant consideration. Lowering LDL-C levels, however, often achieves a favorable effect on HDL-C and triglyceride levels.
Whether or not lipid-modifying drugs are used, nonlipid risk factors require attention and favorable modification. This includes weight reduction and increased physical activity.

15. Initiating LDL-C-lowering therapy in patients hospitalized with acute coronary events
Content Points:
The ATP III guidelines recommend that in persons admitted to the hospital for a major coronary event, LDL-C should be measured on admission or within 24 hours. These values can be used for treatment decisions.
In general, persons hospitalized for a coronary event should be discharged on drug therapy if LDL-C levels are >130 mg/dL. If LDL-C is mg/dL, clinical judgment should be used in deciding whether to initiate drug treatment.
In interpreting LDL-C levels in patients with an acute coronary event, it should be recognized and factored into clinical decisions that LDL-C levels begin to decline in the first few hours after a CHD event, are significantly decreased at 24 to 48 hours, and may remain low for weeks.

16. Advantages of aggressive hospital discharge strategy for LDL-C
Content Points:
ATP III cites important advantages to initiation of LDL-C–lowering therapy at the time the patient is being discharged from the hospital following a CHD-related event.
First, when patients are discharged following a CHD-related illness, they are especially motivated to undertake and adhere to risk-lowering interventions.
Second, failure to initiate indicated therapy at the time patients are discharged from the hospital is a major cause of a large treatment gap because patient follow-up is frequently more fragmented and less consistent than care that is administered in the hospital.
Moreover, early initiation of LDL-C–lowering therapy in patients with acute coronary events improves compliance and may reduce early clinical events and 1-year mortality.
Some authorities maintain that drug therapy should be initiated when a patient hospitalized for a CHD-related illness is found to have an LDL-C >100 mg/dL.

17. ATP III: Diagnosing the metabolic syndrome
Content Points:
ATP III defines the metabolic syndrome as a potential secondary target of therapy. In aggregate, the risk factors for the metabolic syndrome enhance the risk for CHD. ATP III bases the diagnosis of the metabolic syndrome on the presence of 3 or more of the following risk factors: abdominal obesity, elevated triglycerides, low HDL-C, elevated blood pressure, and high fasting glucose level.
Note that ATP III raises the HDL-C cutpoint to <50 mg/dL in women for purposes of defining it as a risk factor. This upward adjustment reflects the general tendency for women to have higher HDL-C levels than men.
Management of the metabolic syndrome has two objectives: (1) to reduce the underlying causes (obesity and physical inactivity) with intensified TLC and (2) to treat associated nonlipid and lipid risk factors.
Patients with the metabolic syndrome frequently are overweight or obese and sedentary. Therefore, treatment should focus on weight reduction and increased physical activity. This approach addresses the underlying causes, obesity or overweight and physical inactivity, and reduces associated lipid and nonlipid risk factors. Reaching the LDL-C target remains the primary goal of treatment.

18. ATP III: Considerations in specific age groups
Content Points:
ATP III includes recommendations for lipid lowering to reduce the risk of coronary disease in a number of special age populations, among which are women aged 45 to 75 years, middle-aged men, and young adults.
Women (aged 45 to 75 years): Although CHD occurs 10 to 15 years later in women than in men, usually after age 65, it is the leading cause of death in women.
ATP III advises against the use of hormone replacement therapy as an alternative to cholesterol-lowering drugs to reduce CHD risk in women. The benefit of hormone replacement therapy for reducing CHD risk is not supported by clinical trials. In contrast, the favorable results achieved with statin therapy in major clinical trials supports the recommendation for statin use to lower LDL-C in women for CHD risk reduction.
Middle-aged men (35-65 years of age): Men in this age group have a high prevalence of CHD risk factors and are prone to abdominal obesity and the metabolic syndrome. For those who have a relatively high CHD risk, ATP III recommends intensive LDL-C–lowering therapy.
Young adults (men years, women years): The foundation for CHD often is laid in adolescence and early adulthood. Elevated serum cholesterol detected in young adults predicts a higher rate of premature CHD in middle age. Therefore, identification and treatment of risk factors in young adults is recommended for long-term prevention of CHD.
For young adults with LDL-C >130 mg/dL, TLC should be emphasized. Young men who smoke with high LDL-C ( mg/dL) and young adults with very high cholesterol (190 mg/dL) should be considered for drug therapy.

19. Focus on elevated triglycerides (>150 mg/dL)
Content Points:
Recent studies indicate that an elevated triglyceride level is significantly linked to the degree of heart disease risk. Therefore, ATP III treatment guidelines have lowered triglyceride levels to give more attention to moderate elevations. Under the revised ATP III guidelines, a triglyceride level of <150 mg/dL is normal, 150 to 199 mg/dL is borderline high, is high, and >500 mg/dL is very high.
For all persons with elevated triglycerides, the primary aim of therapy is to reach the target LDL-C. Therapy includes weight control and physical activity for triglyceride levels above 150 mg/dL.
Non-HDL-C: If triglycerides are above 200 mg/dL after the LDL-C goal is reached, a second goal of non-HDL-C is set. The target non-HDL-C level is calculated by subtracting HDL-C from the total cholesterol level. The final number reflects serum concentrations of LDL-C plus very low density lipoproteins (VLDL-C). The non-HDL-C target is set at 30 mg/dL greater than the LDL-C target.
Drug treatment may be required to reach the non-HDL-C target. Drug therapy may include higher doses of LDL-C-lowering drugs or the addition of nicotinic acid or fibrate to further lower VLDL-C.
Low-HDL-C (not shown on slide): A similar treatment strategy is followed for low HDL-C (<40 mg/dL) if triglycerides are high (>200 mg/dL). However, in cases of isolated low HDL-C consider giving nicotinic acid or fibrate.

20. ATP III: Steps to lipid management—Diagnosis and treatment
Content Points:
Diagnosis step 1. Determine lipoprotein levels by obtaining a complete lipoprotein profile after a 9- to 12-hour fast. This profile includes total cholesterol, LDL-C, HDL-C and triglycerides.
Diagnosis step 2. Identify high-risk patients for more intensive treatment. This group includes patients with CHD and diseases that confer an equivalent risk for a major cardiovascular event (diabetes, other atherosclerotic diseases).
Diagnosis step 3. In patients who do not have CHD or a CHD risk equivalent, determine the number of major cardiovascular risk factors that are present. This step is to help identify candidates for intensive therapy.
Diagnosis step 4. If 2+ risk factors are present without CHD or a CHD risk equivalent, to further stratify this group for treatment, assess the patient’s 10-year CHD risk using Framingham points.
Diagnosis step 5. The patient’s risk category (>20%, <20%, <10%) determines the patient’s LDL-C goal and at what levels to initiate TLC and drug therapy.
Treatment step 1. Initiate TLC if LDL-C is above goal. Focus on TLC, that is diet, weight management, and increased physical activity.
Treatment step 2. Consider drug therapy if LDL-C is above target. Drug therapy and TLC may be initiated concomitantly for patients with CHD and CHD risk equivalents. In lower risk categories, consider drug therapy after 3 months of TLC if the LDL-C target is not achieved.
ATP III recommends initiating LDL-C–lowering therapy for patients hospitalized with CHD-related events and discharging such patients on LDL-C–lowering medications.
Treatment step 3. Identify the presence of multiple metabolic risk factors (the metabolic syndrome). After treating LDL-C, treat the underlying causes of overweight or obesity and physical inactivity with TLC. These measures often lower lipoprotein levels. Lipid and nonlipid risk factors may be treated if they persist after intensive lifestyle therapies are undertaken.
Treatment step 4. For elevated triglycerides ( >150 mg/dL), the primary aim of therapy is to reach the LDL-C goal. Treatment involves intensified weight management and increased physical activity. Intensify drug therapy either by increasing statins or adding fibrates or nicotinic acid. Treatment is similar for low HDL-C in patients with elevated trigycerides. For isolated low HDL-C, consider the use of fibrates.