• To examine the available evidence on coronary heart disease (CHD) and high blood cholesterol, especially the evidence that has emerged since the second report of the Expert Panel was published in 1993 (Second report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel II]. Bethesda [MD]: U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung and Blood Institute; 1993 Sep. 180 p.)
• To update, where appropriate, the existing recommendations for management of high blood cholesterol in adults

2004 Addendum

• To review the results of five recent clinical trials and assess their implications for cholesterol management
• To translate the scientific evidence into guidance that helps professionals and the public take appropriate action to reduce the risk for coronary heart disease and cardiovascular disease

• To promote reduction of cardiovascular risk via evidence-based management of dyslipidemia, thereby improving clinical outcomes
• To assist primary care providers or specialists in the detection of high blood cholesterol, assessment of the global risk for CVD, determination of treatment goals and appropriate therapies, and delivery of individualized intervention
• To incorporate information from several existing, national recommendations into a format that would maximally facilitate clinical decision-making

All adults aged 20 years or older

Adults (age 17 years or older) eligible for care in the VHA/DoD health care system

Advanced Practice Nurses
Dietitians
Nurses
Patients
Pharmacists
Physician Assistants
Physicians
Public Health Departments

Advanced Practice Nurses
Allied Health Personnel
Dietitians
Nurses
Physician Assistants
Physicians

• Fasting lipoprotein profiles (TC, LDL-cholesterol, HDL-cholesterol, and triglyceride)
• Identification of major risk factors as well as life-habit and emerging risk factors
• Estimation of 10-year CHD risk with Framingham scoring

• Patient history and assessment of risk factors for cardiovascular disease, including estimation of 10-year CHD risk with Framingham scoring
• Measurement of TC and HDL or TC, HDL, TG, and LDL
• Fasting lipid profile, including LDL

• Screening should begin at age 20, at the first appropriate opportunity presented by a visit to a physician (case finding), in both men and women.

• Fasting lipid profile testing should be obtained in all men age 35 and older and women age 45 years or older every 5 years. [A] (Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report [NCEP ATP-III], 2002; U.S. Preventive Services Task Force [USPSTF], 2001)
• Fasting lipid profile testing should be obtained in individuals with a family history or clinical evidence of familial hyperlipidemia. [A] (NCEP ATP-III, 2002)
• Fasting lipid profile testing in young adults may be considered depending upon the association with other risk factors. Younger adults (men younger than age 35 and women age 45 or younger) should be screened for lipid disorders if they have one or more of the following risk factors: family history of premature CVD, hypertension (or under treatment for hypertension), or smoking. [B] (NCEP ATP-III, 2002; Pignone et al., 2001; USPSTF, 2001; "A multicenter comparative trial," 1993)
• A lipid profile should be obtained for individuals with abdominal obesity (waist circumference >40 inches in men and >35 inches in women) to aid in assessment of metabolic syndrome. [B] (NCEP ATP-III, 2002)
• All persons with average or below average risk for atherosclerotic events should be screened for dyslipidemia every five years. [I] (Working Group Consensus)
• Elderly patients age 75 or older should be screened if they have multiple CVD risk factors, or a history of CVD and good quality of life with no other major life-limiting diseases. [I] (Working Group Consensus)

• A fasting lipoprotein profile is recommended, including major blood lipid fractions (i.e., total cholesterol, LDL-cholesterol, HDL -cholesterol, and triglycerides).
• If the testing opportunity is nonfasting, only the values for TC and HDL will be usable. In such a case, if total cholesterol is >200 mg/dL or HDL is <40 mg/dL, a follow-up lipoprotein profile is needed for appropriate management based on LDL.

Lipid levels are preferably obtained in a fasting state. However, if the testing opportunity is nonfasting, only the values for TC and HDL will be usable. In otherwise low-risk person (0 to 1 risk factor), further testing is not required if the HDL-C level is >40 mg/dL and TC is <200 mg/dL. For persons with multiple (2+) risk factors, LDL-C levels are needed as a guide to clinical management.

• A complete fasting lipid profile should be obtained in an individual with other risk factors for coronary disease. [A] (USPSTF, 2001)
• Clinical decisions should be based upon lipid profiles done 1 to 8 weeks apart (fasting) with an LDL-C or TC difference of <30 mg/dL. [I] (Working Group Consensus)
• Lipid profiles should not be obtained within 8 weeks of acute hospitalization, surgery, trauma, or infection unless they are obtained within 12 to 24 hours of the event to ensure accuracy. [I] (Working Group Consensus)
• Lipid profiles should not be measured in pregnant women until three to four months post partum. [I] (Working Group Consensus)

Lipid Screening Test

• Ensure test is obtained in fasting state (9 to 14 hour fast)
• TC, TG, and HDL-C are measured directly
• LDL-C is calculated; therefore, TG level should be considered

  (If TG >400 mg/dL, try to reduce with diet and exercise, or consider direct measurement of LDL-C)

• Assessment of major risk factors* (exclusive of LDL-cholesterol) that modify LDL goals is recommended. Factors to assess include:
  • Cigarette smoking
  • Hypertension
  • Low HDL-cholesterol (<40 mg/dL)**
  • Family history of premature CHD
  • Age (men >45 years, women >55years)

  *Diabetes is regarded as a CHD risk equivalent.

  **HDL cholesterol >60 mg/dL counts as a "negative" risk factor; its presence removes 1 risk factor from the total count

• A 10-year risk assessment using Framingham scoring in persons identified to have multiple (2+) risk factors is recommended in order to identify individuals whose short-term (10-year) risk warrants consideration of intensive treatment.
• In addition, assessment of life-habit risk factors and emerging risk factors is recommended. The former include obesity, physical inactivity, and atherogenic diet; the later consist of lipoprotein (a), homocysteine, prothrombotic and proinflammatory factors, impaired fasting glucose, and evidence of subclinical atherosclerotic disease.

2004 Addendum

• Lifestyle-related risk factors include obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome.

1. Patients screened for dyslipidemia should be assessed for risk factors for CVD. Assessment should include, but not be limited to, the following:
   1. Age (males >age 45 and females >age 55)
   2. Family history of premature coronary artery disease; definite myocardial infarction (MI) or sudden death before age 55 in father or other male first-degree relative, or before age 65 in mother or other female first-degree relative
   3. Current tobacco use/cigarette smoking (or within the last month)
   4. Hypertension (systolic BP >140 mmHg or diastolic BP >90 mmHg confirmed on more than one occasion, or current therapy with anti-hypertensive medications)
   5. Diabetes mellitus (elevated fasting blood sugar [>126 mg/dL], or a random blood sugar [>200 mg/dL] confirmed on more than one occasion, an abnormal glucose tolerance test or current therapy with anti-diabetic medications)
   6. Level of HDL-C (less than 40 mg/dL confirmed on more than one occasion)
2. In obese patients (body mass index >30), waist circumference measurement should be obtained to assist in the diagnosis of metabolic syndrome.

10-Year Risk Score for CVD

• A global 10-year risk for CVD should be calculated to assess the short-term (10-year) absolute risk of a CVD event. [A] (Grover, Coupal, & Hu, 1998; Grover et al., 2000; Grundy et al., 2004)
• The Framingham Risk Calculator should be used, as it is the most commonly used and readily available calculator validated in numerous populations. [I] (Grundy et al., 1999; Sheridan, Pignone, & Mulrow, 2003; Wilson et al., 1998) http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof
• Other risk markers or measure of atherosclerotic burden may be useful to adjust the risk category, if they have been validated to have independent prognostic value. [C] (Ford et al., 1998; Greenland et al., 2000 & 2004; O'Donnel, 2004; Pearson et al., 2003; Pletcher et al., 2004; Ridker, 2001)

ATP III Classification of LDL, Total, and HDL-Cholesterol (mg/dL)

• LDL-cholesterol — (primary target of therapy)
  <100 Optimal
  100 to 129 Near Optimal/Above Optimal
  130 to 159 Borderline High
  160 to 189 High
  >190 Very high
• Total cholesterol
  <200 Desirable
  200 to 239 Borderline High
  >240 High
• HDL-cholesterol
  <40 Low
  >60 High

• Classify serum lipid levels based on degree of elevation of LDL, TG, or low HDL. [C] (NCEP ATP-III, 2002)
• Total Cholesterol (mg/dL) (mmol/L)
  <200 (<5.2) Normal
  200 to 239 (5.2 to 6.1) Borderline High
  >240 (>6.2) High
• LDL-C (mg/dL) (mmol/L)
  <100 (<2.6) Normal
  100 to 129 (2.6 to 3.3) Above, near optimal
  130 to 159 (3.4 to 4.0) Borderline High
  160 to 189 (4.1 to 4.8) High
  >190 (>4.9) Very High
• HDL-C (mg/dL) (mmol/L)
  <40 (<1.0) Low
  >60 (>1.6) High
• Triglycerides (mg/dL) (mmol/L)
  <150 mg/dL (<1.7) Normal
  150 to 199 mg/dL (1.7 to 2.2) Borderline High
  200 to 499 mg/dL (2.3 to 5.6) High
  >500 mg/dL (>5.6) Very High
  

• If an initial nonfasting test reveals a total cholesterol >200 mg/dL or an HDL <40mg/dL, a follow-up lipoprotein profile is needed for appropriate management based on LDL.
• Any person with elevated LDL-cholesterol or other form of hyperlipidemia should undergo clinical or laboratory assessment to rule out secondary dyslipidemia before initiation of lipid-lowering therapy. Causes of secondary dyslipidemia include diabetes, hypothyroidism, obstructive liver disease, chronic renal failure, and certain drugs (e.g., progestins, anabolic steroids, corticosteroids).
• Framingham projections of 10-year absolute CHD risk are used to identify certain patients with multiple (2+) risk factors for more intensive treatment.
• Patients who are identified with multiple metabolic risk factors (metabolic syndrome) are candidates for intensified therapeutic lifestyle changes.
• ATP III identifies three categories of risk that modify the goals and modalities of LDL-lowering therapy (see also relevant changes noted in the 2004 addendum presented below).
  • CHD and CHD risk equivalents: LDL goal <100 mg/dL
  • Multiple (2+) risk factors: LDL goal <130 mg/dL
  • Zero to one risk factor: LDL goal <160 mg/dL
• LDL goals in primary prevention depend on a person's absolute risk for CHD (i.e., the probability of having a CHD event in the short term or the long term)—the higher the risk, the lower the goal. Therapeutic lifestyle changes are the foundation of clinical primary prevention. Nonetheless, some persons at higher risk because of high or very high LDL cholesterol levels or because of multiple risk factors are candidates for LDL-lowering drugs. Recent primary prevention trials show that LDL-lowering drugs reduce risk for major coronary events and coronary death even in the short term (see also relevant changes noted in the 2004 addendum presented below).

2004 Addendum

The ATP III goals and cutpoints for therapeutic lifestyle changes and drug therapy in different risk categories, and proposed modifications in the treatment algorithm for LDL cholesterol based on evidence from recent clinical trials, are presented below. Essential modifications are highlighted in the footnotes and summary that follow.

Risk Category: High risk: CHD¹ or CHD risk equivalents² (10-year risk >20%)

• LDL-C Goal: <100 mg/dL (optional goal: <70 mg/dL)⁶
• Initiate TLC: >100 mg/dL⁸
• Consider Drug Therapy⁹: >100 mg/dL10 (<100 mg/dL: consider drug options)⁹

Risk Category: Moderately high risk: 2+ risk factors³ (10-year risk 10% to 20%)⁴

• LDL-C Goal: <130 mg/dL⁷
• Initiate TLC: >130 mg/dL⁸
• Consider Drug Therapy⁹: >130 mg/dL (100 to 129 mg/dL: consider drug options)¹¹

Risk Category: Moderate risk: 2+ risk factors³ (10-year risk <10%)⁴

• LDL-C Goal: <130 mg/dL
• Initiate TLC: >130 mg/dL
• Consider Drug Therapy⁹: >160 mg/dL

Risk Category: Lower risk: 0 to 1 risk factor⁵

• LDL-C Goal: <160 mg/dL
• Initiate TLC: >160 mg/dL
• Consider Drug Therapy⁹: >190 mg/dL (160-189 mg/dL: LDL-lowering drug optional)

¹Coronary heart disease (CHD) includes history of myocardial infarction, unstable angina, stable angina, coronary artery procedures (angioplasty or bypass surgery), or evidence of clinically significant myocardial ischemia.

²CHD risk equivalents include clinical manifestations of noncoronary forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease [transient ischemic attacks or stroke of carotid origin or >50% obstruction of a carotid artery]), diabetes, and 2+ risk factors with 10-year risk for hard CHD >20%.

³Risk factors include cigarette smoking, hypertension (BP >140/90 mm Hg or on antihypertensive medication), low high-density lipoprotein (HDL) cholesterol (<40 mg/dL), family history of premature CHD (CHD in male first-degree relative <55 years of age; CHD in female first-degree relative <65 years of age), and age (men >45 years; women >55 years).

⁴Electronic 10-year risk calculators are available at www.nhlbi.nih.gov/guidelines/cholesterol.

⁵Almost all people with zero or 1 risk factor have a 10-year risk <10%, and 10-year risk assessment in people with zero or 1 risk factor is thus not necessary.

⁶Very high risk favors the optional LDL-C goal of <70 mg/dL, and in patients with high triglycerides, non-HDL-C <100 mg/dL.

⁷Optional LDL-C goal <100 mg/dL.

⁸Any person at high risk or moderately high risk who has lifestyle-related risk factors (e.g., obesity, physical inactivity, elevated triglyceride, low HDL-C, or metabolic syndrome) is a candidate for therapeutic lifestyle changes to modify these risk factors regardless of LDL-C level.

⁹When LDL-lowering drug therapy is employed, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels.

¹⁰If baseline LDL-C is <100 mg/dL, institution of an LDL-lowering drug is a therapeutic option on the basis of available clinical trial results. If a high-risk person has high triglycerides or low HDL-C, combining a fibrate or nicotinic acid with an LDL-lowering drug can be considered.

¹¹For moderately high-risk persons, when LDL-C level is 100 to 129 mg/dL, at baseline or on lifestyle therapy, initiation of an LDL-lowering drug to achieve an LDL-C level <100 mg/dL is a therapeutic option on the basis of available clinical trial results.

Summary of Modifications

• Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. TLC has the potential to reduce cardiovascular risk through several mechanisms beyond LDL lowering.
• In high-risk persons, the recommended LDL-C goal is <100 mg/dL.
  • An LDL-C goal of <70 mg/dL is a therapeutic option on the basis of available clinical trial evidence, especially for patients at very high risk.
  • If LDL-C is >100 mg/dL, an LDL-lowering drug is indicated simultaneously with lifestyle changes.
  • If baseline LDL-C is <100 mg/dL, institution of an LDL-lowering drug to achieve an LDL-C level <70 mg/dL is a therapeutic option on the basis of available clinical trial evidence.
  • If a high-risk person has high triglycerides or low HDL-C, consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. When triglycerides are >200 mg/dL, non-HDL-C is a secondary target of therapy, with a goal 30 mg/dL higher than the identified LDL-C goal.
• For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL; an LDL-C goal <100 mg/dL is a therapeutic option on the basis of available clinical trial evidence. When LDL-C level is 100 to 129 mg/dL, at baseline or on lifestyle therapy, initiation of an LDL-lowering drug to achieve an LDL-C level <100 mg/dL is a therapeutic option on the basis of available clinical trial evidence.
• Any person at high risk or moderately high risk who has lifestyle-related risk factors (e.g., obesity, physical inactivity, elevated triglyceride, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level.
• When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels.
• For people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.

• Patients with LDL >130 mg/dL, HDL <40 mg/dL, or TG >200 mg/dL should be assessed for further management of dyslipidemia. [C] (NCEP ATP-III, 2002)
• Goals of lipid lowering therapy should be tailored to risk level and based upon the balance between benefits, risks, and patient preferences. [C] (27th Bethesda Conference, 1996; Grundy et al., 2004)
• Adults with abnormal lipid profiles (dyslipidemia) should be assessed for secondary causes, familial disorders, and other underlying conditions that may influence lipid levels. [I] (NCEP ATP-III, 2002; Stone, Blum, & Winslow, 1997; Stone & Blum, 2002)

Non-Pharmacologic Therapy

• TLC should be recommended for ALL patients with dyslipidemia, regardless of risk or baseline LDL-C level. [C]

Goals of Therapy for Primary Prevention

• LDL-C should be lowered to <100 mg/dL for patients with high 10-year risk >20 percent. [B] (Sever et al., 2003; Heart Protection Study Collaborative Group, 2002; "Screening experience and baseline characteristic in the West of Scotland Coronary Prevention Study," 1995)
• LDL-C should be lowered to <130 mg/dL for patients with intermediate 10-year risk (15 to 20 percent). [B] (Downs et al., 1998)
• LDL-C should be lowered to <130 mg/dL for patients with intermediate 10-year risk (10 to 14 percent). [C] (NCEP ATP-III, 2002)
• LDL-C should be lowered to <160 mg/dL for patients with low 10-year risk. [I] (Working Group Consensus)
• LDL-C reduction of 30 to 40 percent from baseline may be considered an alternative therapeutic strategy for patients who cannot meet the above goal

Drug Therapy for Primary Prevention

• Drug therapy should be initiated for high-risk patients (>20%) if baseline LDL is >130 mg/dL. [B] (Downs et al., 1998; Sever et al., 2003; "Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study," 1995)
• Drug therapy is optional to consider in high-risk patients (>20%) if baseline LDL is 100 to 129 mg/dL. [B] (Heart Protection Study Collaborative Group, 2002)
• Drug therapy may be offered to patients with high-intermediate risk (15 to 20 percent) if baseline LDL is >130 mg/dL. [B] (Downs et al., 1998; Sever et al., 2003; "Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study," 1995)
• Drug therapy may be offered to patients with low-intermediate risk (10 to 14 percent) if baseline LDL is >160 mg/dL. [C] (NCEP ATP-III, 2002)
• Drug therapy may be offered to low-risk patients (<10 percent) if baseline LDL is >190 mg/dL. [I] (NCEP ATP-III, 2002)

• Screening is recommended every 5 years unless more frequent testing is warranted.
• Follow-up lipoprotein analysis should be carried out according to the following schedule:
  • In patients with 2+ risk factors whose LDL levels are observed at <130 mg/dL, lipoprotein analysis should be repeated <2 years;
  • In patients with 0 to 1 risk factors whose LDL levels are observed at 130 to 159 mg/dL, lipoprotein analysis should be repeated <2 years,
  • In patients with 0 to 1 risk factors whose LDL levels are observed at <130 mg/dL, lipoprotein analysis should be repeated <5 years.

• Patients with average or below average risk for atherosclerotic events should be screened for dyslipidemia every five years. [B] (NCEP ATP-III, 2002; "A multicenter comparative trial," 1993)
• If the initial dyslipidemia screening reveals TC >200 mg/dL, or fasting LDL-C >130 mg/dL or HDL-C <40 mg/dL, but LDL-C level is under the recommended goal level based upon cardiovascular risk, the patient will be at low-risk for lipid-related events over a one to two-year period and thus, should be reevaluated for dyslipidemia in one to two years.

Recommended Screening Schedules for Dyslipidemia

For young adults (men <age 35; women <age 45)

• Every 5 years when no CVD risk factors are present
• More often, if family history of premature CVD exists (definite myocardial infarction or sudden death before 55 years of age in father or other male first-degree relative or before age 65 in mother or other female first-degree relative)

For middle-aged adults (men >age 35; women >age 45)

• Every 5 years, when no CVD risk factors are present
• Annually, if CVD risk factors exist (hypertension, smoking, family history of premature CVD)

For elderly patients up to age 75 years

• Every 5 years when no CVD risk factors are present
• More often if CVD risk factors exist

For elderly patients >age 75

• Evaluate if patient has multiple CVD risk factors, established CVD, or a history of revascularization procedures and good quality of life with no other major life-limiting diseases.

By adopting the clinical high-risk CHD prevention strategy, individuals at significantly increased risk are identified and treated, thus reducing the individual's risk for CHD and reducing the overall burden of CHD. The clinical high-risk strategy and the population strategy, which seeks to lower average blood cholesterol levels in the whole population by promoting changes in dietary patterns and physical activity levels, are complementary. Both strategies are incorporated into the National Cholesterol Education Program and together reduce the societal burden of CHD.

2004 Addendum

Since the publication of ATP III, 5 major clinical trials of statin therapy have confirmed the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C.

Lipid-related risk factors for ASCVD include high levels of total cholesterol or LDL-C) and low levels of HDL-C). Other risk factors include age, male sex, high blood pressure, tobacco use, diabetes mellitus, and family history of premature coronary heart disease. Because the range of CVD 10-year absolute risk is wide, targeted screening for patients at high absolute risk to develop CVD is recommended. All adults—regardless of age—with a history of CVD should undergo lipoprotein screening. For asymptomatic individuals (i.e., for primary prevention), available evidence supports cholesterol screening only if other characteristics place them at high-risk. Targeted screening to identify these risk factors will allow for lipid-related interventions to reduce the risk of ASVCD.

Not stated

Not stated

Type of Evidence:

1. Major randomized controlled trials
2. Smaller randomized controlled trials and meta-analyses of other clinical trials
3. Observational and metabolic studies
4. Clinical experience

Strength of Evidence:

1. Very strong evidence
2. Moderately strong evidence
3. Strong trend

Strength of the Recommendations

A: A strong recommendation that the clinicians provide the intervention to eligible patients.
Good evidence was found that the intervention improves important health outcomes and concludes that benefits substantially outweigh harm.

B: A recommendation that clinicians provide (the service) to eligible patients.
At least fair evidence was found that the intervention improves health outcomes and concludes that benefits outweigh harm.

C: No recommendation for or against the routine provision of the intervention is made.
At least fair evidence was found that the intervention can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.

D: Recommendation is made against routinely providing the intervention to asymptomatic patients.
At least fair evidence was found that the intervention is ineffective or that harms outweigh benefits.

I: The conclusion is that the evidence is insufficient to recommend for or against routinely providing the intervention.
Evidence that the intervention is effective is lacking, or poor quality, or conflicting and the balance of benefits and harms cannot be determined.

Quality of Evidence

I: At least one properly done randomized controlled trial

II-1: Well designed controlled trails without randomization

II-2: Well designed cohort or case-control analytic study, preferably from more than one source

II-3: Multiple time series evidence with/without intervention; dramatic results of uncontrolled experiment

III: Opinion of respected authorities, descriptive studies, case reports, and expert committees

Overall Quality

Good: High grade evidence (I or II-1) directly linked to health outcome

Fair: High grade evidence (I or II-1) linked to intermediate outcome; or moderate grade evidence (II-2 or II-3) directly linked to health outcome

Poor: Level III evidence or no linkage of evidence to health outcome.

Net Effect of Intervention

Substantial:

• More than a small relative impact on a frequent condition with a substantial burden of suffering, or
• A large impact on an infrequent condition with a significant impact on the individual patient level

Moderate:

• A small relative impact on a frequent condition with a substantial burden of suffering, or
• A moderate impact on an infrequent condition with a significant impact on the individual patient level

Small:

• A negligible relative impact on a frequent condition with a substantial burden of suffering, or
• A small impact on an infrequent condition with a significant impact on the individual patient level

Zero or Negative:

• Negative impact on patients, or
• No relative impact on either a frequent condition with a substantial burden of suffering, or
• An infrequent condition with a significant impact on the individual patient level

References Supporting the Recommendations

27th Bethesda Conference. Matching the Intensity of Risk Factor Management with the Hazard for Coronary Disease Events. September 14-15, 1995. J Am Coll Cardiol 1996 Apr;27(5):957-1047. PubMed

A multicenter comparative trial of lovastatin and pravastatin in the treatment of hypercholesterolemia. The Lovastatin Pravastatin Study Group. Am J Cardiol 1993 Apr 1;71(10):810-5. PubMed

Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM Jr. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998 May 27;279(20):1615-22. PubMed

Ford DE, Mead LA, Chang PP, Cooper-Patrick L, Wang NY, Klag MJ. Depression is a risk factor for coronary artery disease in men: the precursors study. Arch Intern Med 1998 Jul 13;158(13):1422-6. PubMed

Greenland P, Abrams J, Aurigemma GP, Bond MG, Clark LT, Criqui MH, Crouse JR 3rd, Friedman L, Fuster V, Herrington DM, Kuller LH, Ridker PM, Roberts WC, Stanford W, Stone N, Swan HJ, Taubert KA, Wexler L. Prevention Conference V: beyond secondary prevention: identifying the high-risk patient for primary prevention: noninvasive tests of atherosclerotic burden: Writing Group III. Circulation 2000 Jan 4;101(1):E16-22. PubMed

Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA 2004 Jan 14;291(2):210-5. PubMed

Grover SA, Coupal L, Hu XP. Identifying adults at increased risk of coronary disease. How well do the current cholesterol guidelines work?. JAMA 1995 Sep 13;274(10):801-6. PubMed

Grover SA, Dorais M, Paradis G, Fodor JG, Frohlich JJ, McPherson R, Coupal L, Zowall H. Lipid screening to prevent coronary artery disease: a quantitative evaluation of evolving guidelines. CMAJ 2000 Nov 14;163(10):1263-9. PubMed

Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004 Jul 13;110(2):227-39. [45 references] PubMed

Grundy SM, Pasternak R, Greenland P, Smith S Jr, Fuster V. Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology. Circulation 1999 Sep 28;100(13):1481-92. [115 references] PubMed

Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002 Jul 6;360(9326):7-22. PubMed

O'Donnell CJ. Family history, subclinical atherosclerosis, and coronary heart disease risk: barriers and opportunities for the use of family history information in risk prediction and prevention. Circulation 2004 Oct 12;110(15):2074-6. PubMed

Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003 Jan 28;107(3):499-511. PubMed

Pignone MP, Phillips CJ, Atkins D, Teutsch SM, Mulrow CD, Lohr KN. Screening and treating adults for lipid disorders. Am J Prev Med 2001 Apr;20(3 Suppl):77-89. [62 references] PubMed

Pletcher MJ, Tice JA, Pignone M, Browner WS. Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis. Arch Intern Med 2004 Jun 28;164(12):1285-92. PubMed

Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001 Apr 3;103(13):1813-8. PubMed

Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study. The WOSCOPS Study Group. West of Scotland Coronary Prevention Study. Am J Cardiol 1995 Sep 1;76(7):485-91. PubMed

Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinian Cardiac Outcomes Trial - Lipid Lowering Arm (ASCOT-LLA): a multicentre [trunc]. Lancet 2003 Apr 5;361(9364):1149-58. PubMed

Sheridan S, Pignone M, Mulrow C. Framingham-based tools to calculate the global risk of coronary heart disease: a systematic review of tools for clinicians. J Gen Intern Med 2003 Dec;18(12):1039-52. [58 references] PubMed

Stone NJ, Blum C, Winslow E. Management of lipids in clinical practice. Oklahoma: Professional Communications Inc.; 1997.

Stone NJ, Blum CB. Management of lipids in clinical practice. West Islip (NY): Professional Communications Inc.; 2002. 115-20 p.

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002 Dec 17;106(25):3143-421. PubMed

US Preventive Services Task Force. Screening adults for lipid disorders: recommendations and rationale. Am J Prev Med 2001 Apr;20(3 Suppl):73-6. PubMed

Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998 May 12;97(18):1837-47. PubMed