ATP III Guidelines

1
ATP III Guidelines

• Janet B. Long, MSN, ACNP, CLS, FAHA
• Preventive Cardiovascular Nurses Association

2
NCEP ATP Guidelines Provide a Framework to Reduce
CHD Risk

• NCEP ATP I (1988)
• Primary prevention focus
• Primary goal LDL-C ?
• NCEP ATP II (1993)
• Affirmed approach outlined in ATP I
• LDL-C goal in patients with established CAD
  ?100 mg/dL
• NCEP ATP III (2001)
• Focus on multiple risk factors

Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA. 20012852486.
3
Comparison of Major Features of ATP II and ATP
III
ATP II
ATP III
LDL-C target for CHD or CHD Risk Equivalent
100 mg/dL
lt 100 mg/dL
LDL-C target for very high cholesterol
³ 220 mg/dL
³ 190 mg/dL
Categorically low HDL-C
lt 35 mg/dL
lt 40 mg/dL
Triglycerides
lt 200 mg/dL
lt 150 mg/dL
Risk Factor
CHD Equivalent
Diabetes
Completion of Framingham Risk Assessment
No
Yes
Total-C, HDL-C, LDL-C, and TG
Recommended lipid profile
Total-C and HDL-C
Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA. 19932693015. Expert Panel on Detection,
Evaluation, and Treatment of High Blood
Cholesterol in Adults. JAMA. 20012852486.
4
Primary New Features of ATP III

• Diabetes considered a CHD risk equivalent
• Uses Framingham projections of 10-year absolute
  risk to identify certain patients with multiple
  (2) risk factors for more intensive treatment
• Identifies patients with metabolic syndrome as
  candidates for intensified therapeutic lifestyle
  changes (TLC)

Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA. 20012852486.
5
Identification of CHD Risk Equivalents

• Diabetes
• Atherosclerotic disease
• Peripheral artery disease
• Abdominal aortic aneurysm
• Symptomatic carotid artery disease
• CHD 10-year risk gt20

Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA. 20012852486.
6
ATP III Classification of LDL, Total and
HDL Cholesterol (mg/dl)
LDL cholesterol lt 100
Optimal 100 - 129
Near or above
optimal 130 - 159
Borderline high 160 - 189
High ? 190
Very
High Total cholesterol lt 200
Desirable 200
- 249
Borderline high ? 240
High HDL cholesterol
lt 40
Low ? 60
High
NCEP ATP III. JAMA, May 16, 2001 - Vol 285, No.
19.
7
Major Risk Factors (Exclusive of LDL
Cholesterol) That Modify LDL Goals

• Cigarette smoking
• Hypertension (BP ?140/90 mmHg or on
  antihypertensive medication)
• Low HDL cholesterol (lt40 mg/dL)
• Family history of premature CHD
• CHD in male first degree relative lt55 years
• CHD in female first degree relative lt65 years
• Age (men ?45 years women ?55 years)

HDL cholesterol ?60 mg/dL counts as a
negative risk factor its presence removes one
risk factor from the total count.
8
Primary Prevention

• Goals of Therapy
• Long-term prevention (gt10 years)
• Short-term prevention (?10 years)

9
Primary New Features of ATP III

• Diabetes considered a CHD risk equivalent
• Uses Framingham projections of 10-year absolute
  risk to identify certain patients with multiple
  (2) risk factors for more intensive treatment
• Identifies patients with metabolic syndrome as
  candidates for intensified therapeutic lifestyle
  changes (TLC)

Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA. 20012852486.
10
Risk Assessment

• Count major risk factors
• For patients with multiple (2) risk factors
• Perform 10-year risk assessment
• For patients with 01 risk factor
• 10 year risk assessment not required
• Most patients have 10-year risk lt10

11
Estimate of 10-Year Risk for Men
(Framingham Point Scores)
1
Age Age Age Age
Age 20-39 40-49 50-59 60-69
70-79
3
5
Systolic BP If If mm Hg
Untreated Treated
Age, y Points
Nonsmoker 0 0 0
0 0 Smoker 8
5 3 1 1
20-34 -9 35-39
-4 40-44
0 45-49 3 50-54
6 55-59
8 60-64
10 65-69 11 70-74
12 75-79
13
lt 120 0 0 120-129
0 1 130-139
1 2 140-159 1
2 ?160 2
3
Point Total 10-Year Risk
6
lt 0 lt 1 0
1 1
1 2
1 3
1 4
1 5
2 6
2 7
3 8
4 9
5 10
6 11
8 12
10 13
12 14
16 15
20 16
25 ? 17 ? 30
4
HDL, mg/dl Points
? 60 -1 50-59
0 40-49 1
lt40 2
2
Total Age Age Age
Age Age Cholesterol 20-39
40-49 50-59 60-69 70-79
lt 160 0 0
0 0 0 160-199
4 3 2 1
0 200-239 7 5
3 1 0 240-279
9 6 4 2
1 ? 280 11 8
5 3 1
NCEP ATP III. JAMA, May 16, 2001 - Vol 285, No.
19.
12
Estimate of 10-Year Risk for Women
(Framingham Point Scores)
1
3
5
Systolic BP If If mm Hg
Untreated Treated
Age Age Age Age
Age 20-39 40-49 50-59 60-69
70-79
Age, y Points
20-34 -7 35-39
-3 40-44
0 45-49 3 50-54
6 55-59
8 60-64
10 65-69 12 70-74
14 75-79
16
lt 120 0 0 120-129
1 3 130-139
2 4 140-159 3
5 ?160 4
6
Nonsmoker 0 0 0
0 0 Smoker 9
7 4 2 1
6
Point Total 10-Year Risk,
lt 9 lt 1 9
1 10
1 11
1 12
1 13
2 14
2 15
3 16
4 17
5 18
6 19
8 20
11 21
14 22
17 23
22 24
27 ? 25 ? 30
4
HDL, mg/dl Points
? 60 -1 50-59
0 40-49 1
lt40 2
2
Total Age Age Age
Age Age Cholesterol 20-39
40-49 50-59 60-69 70-79
lt 160 0 0
0 0 0 160-199
4 3 2 1
1 200-239 8 6
4 2 1 240-279
11 8 5 3
2 ? 280 13 10
7 4 2
NCEP ATP III. JAMA, May 16, 2001 - Vol 285, No.
19.
13
Three Categories of Risk That Modify
LDL Cholesterol Goals
Risk Category LDL Goal
(mg/dl
CHD and CHD Risk equivalents
lt 100 Multiple (2) risk factors
lt 130 0 - 1 risk
factor
lt 160
NCEP ATP III. JAMA, May 16, 2001 - Vol 285, No.
19.
14
Primary New Features of ATP III

• Diabetes considered a CHD risk equivalent
• Uses Framingham projections of 10-year absolute
  risk to identify certain patients with multiple
  (2) risk factors for more intensive treatment
• Identifies patients with metabolic syndrome as
  candidates for intensified therapeutic lifestyle
  changes (TLC)

Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA. 20012852486.
15
NCEP ATP III Cholesterol Guidelines

• Additional Emphasis
• Recognizes metabolic syndrome as secondary target
  for risk reduction therapy after weight reduction
  increased physical activity
• Recommends treatment beyond LDL reduction for pts
  with TG gt200 mg/dl
• For pts with TG ? 200 mg/dl, non-HDL (TC - HDL)
  with be a secondary target after weight reduction
  increased physical activity

Journal of the American Medical Association, May
16, 2001
16
The Metabolic Syndrome NCEP ATP III Criteria

• Risk Factor Defining Level
• Abdominal obesity
• Men Waist ? 40 inches
• Women Waist ? 35 inches
• Triglycerides ? 150 mg/dL
• HDL cholesterol
• Men ? 40 mg/dL
• Women ? 50 mg/dL
• Blood pressure ? 130/ ? 85 mm Hg
• Fasting glucose ? 110 mg/dL

NCEP ATP III. Circulation. 20021063145-3421.
17
The Metabolic Syndrome

• Incidence is rapidly increasing in the US and
  other countries related to increasing obesity
• Characterized by a constellation of underlying
  causes and metabolic risk factors
• Risk for developing CHD exceeds that predicted by
  LDL-C only or Framingham Risk Score

NCEP ATP III. Circulation. 20021063145-3421.
18
The Metabolic Syndrome
Endothelial
Complex
Systemic
Dysfunction
Dyslipidemia
Inflammation
TG, LDL
HDL
Athero- sclerosis
Insulin
Disordered
Resistance
Fibrinolysis
Hypertension
Visceral
Obesity
Type 2 Diabetes
Adapted from the ADA. Diabetes Care.
199821310-314 Pradhan AD et al. JAMA.
2001286327-334.
19
The Metabolic Syndrome and TLC

• Greatest benefit from successful implementation
  of therapeutic lifestyle change (TLC) will occur
  in this group of patients
• Prioritize limited resources for implementing TLC
  in these patients

NCEP ATP III. Circulation. 20021063145-3421.
20
Incorporating the Metabolic Syndrome in Risk
Assessment and Management

• Presence of the metabolic syndrome may be
  indication for more aggressive lipid lowering
  LDL lt 100 mg/dL, TG lt 150 mg/dL, HDL gt 40 mg/dL
• Options statins as first choice
• Add drugs that lower triglycerides and raise HDL
  nicotinic acid or fibrates plus statin
• Target nonHDL-C as goal of treatment(lt 130
  mg/dL)

21
Essential Components of TLC
Component Recommendation
NCEP ATP III. Circulation. 20021063145-3421.
22
Macronutrient Recommendations for the TLC Diet
Component Recommendation
Polyunsaturated fat
Up to 10 of total calories
Monounsaturated fat
Up to 20 of total calories
Total fat
25?35 of total calories
Carbohydrate
50?60 of total calories
Dietary fiber
20?30 grams per day
Protein
Approximately 15 of total calories
NCEP ATP III allows an increase of total fat to
35 of total calories and a reduction in
carbohydrate to 50 for persons with the
metabolic syndrome. Any increase in fat intake
should be in the form of either polyunsaturated
or monounsaturated fat. Carbohydrate should
derive predominantly from foods rich in complex
carbohydrates including grains, especially whole
grains, fruits, and vegetables.
NCEP ATP III. Circulation 2002106 3145-3421.
23
Treatment of the Metabolic Syndrome

• Correct atherogenic dyslipidemia
• Elevated triglycerides
• Low HDL-C
• Small, dense LDL particles
• Correct hypertension
• Aspirin for prothrombotic state
• LDL-C reduction alone does not result in full
  benefit

NCEP ATP III. Circulation. 20021063145-3421.
24
Treatment of the Metabolic Syndrome (cont)

• Correct insulin resistance
• Weight reduction
• Increased physical activity
• Drugs which decrease insulin resistance have not
  been proven to reduce CHD risk
• Control diabetes mellitus

NCEP ATP III. Circulation. 20021063145-3421.
25
Drug Therapy of the Metabolic Syndrome

• Decrease small, dense LDL particles
• Statins
• Nicotinic acid (niacin)
• Fibrates
• (Statins may be more effective in reducing
  total number of LDL particles)
• Decrease triglycerides
• Fibrates
• Omega-3 fatty acid
• Nicotinic acid (niacin)
• Statins
• Increase HDL-C
• Nicotinic acid (niacin)
• Fibrates, especially if hypertriglyceridemia is
  present

NCEP ATP III. Circulation. 20021063145-3421.
26
Summary of the Metabolic Syndrome

• Diagnosis indicates a high-risk patient beyond
  that classically defined by risk factor
  assessment
• Achieve LDL-C target goals
• Control atherogenic dyslipidemia
• Weight loss and increased physical activity
  deserve a high priority

NCEP ATP III. Circulation. 20021063145-3421.
27
Treatment of Elevated Triglycerides (? 150 mg/dL)

• Primary aim of therapy is to reach LDL goal
• Intensify weight management
• Increase physical activity
• If TG ? 200 mg/dL after LDL goal is reached, set
  secondary goal for non-HDL cholesterol
• Non-HDL TC HDL

NCEP ATP III. Circulation. 20021063145-3421.
28
Treatment of Low HDL (lt 40 mg/dL)

• First reach LDL goal
• Intensify weight management and increase physical
  activity
• If TG 200499 mg/dL, achieve non-HDL goal
• If TG lt 200 mg/dL (isolated low HDL) in CHD or
  equivalent, consider nicotinic acid or fibrate

NCEP ATP III. Circulation. 20021063145-3421.
29
If Triglycerides Are 200?499 mg/dL After LDL
Goal Reached

• Consider adding drug if needed to reach non-HDL
  goal
• Intensify therapy with LDL lowering drug, or
• Add nicotinic acid or fibrate to further
  lower VLDL

NCEP ATP III. Circulation. 20021063145-3421.
30
If Triglycerides ? 500 mg/dL

• First lower TG to prevent pancreatitis
• Very low-fat diet (? 15 calories from fat)
• Weight management
• Fibrate or nicotinic acid
• When TG lt 500 mg/dL, turn to LDL lowering therapy

NCEP ATP III. Circulation. 20021063145-3421.
31
Cholesterol Management Pharmacotherapy
HDL-CHigh-density lipoprotein cholesterol,
LDL-CLow-density lipoprotein cholesterol,
TCTotal cholesterol, TGTriglycerides Daily
dose of 40mg of each drug, excluding rosuvastatin.
32
2004 Recommendations
33
Trials Published Since ATP III Key Results

• Since ATP III, 7 major clinical end point trials
  of statin therapy have been published (the Heart
  Protection Study, PROSPER, ALLHAT-LLT, ASCOT-LLA,
  PROVE IT, CARDS, and TNT)1-8
• Results from these trials
• Confirm the benefit and safety of statins,
  particularly among high-risk patients2-5,7
• Indicate that more intensive LDL-Clowering
  therapy provides a greater benefit than less
  intensiveLDL-Clowering therapy1,3,8
• Suggest that reducing LDL-C substantially below
  100 mg/dL provides additional benefit3,8

1. Grundy et al. Circulation. 2004110227-239
2. Heart Protection Study Collaborative Group.
Lancet. 20023607-22 3. Cannon et al. N Engl J
Med. 20043501495-1504 4. Shepherd et al.
Lancet. 20023601623-1630 5. Sever et al.
Lancet. 20033611149-1158 6. ALLHAT Officers
and Coordinators for the ALLHAT Collaborative
Research Group. JAMA. 20022882998-3007 7.
Colhoun et al on behalf of the CARDS
investigators. Lancet. 2004364685-696 8.
LaRosa et al for the TNT Investigators. N Engl J
Med. 2005352.
34
NCEP Interim Report LDL-C Goals and Drug Cut
Points for High-Risk Patients
LDL-C Goal (mg/dL)
LDL-C to Consider Drug Therapy (mg/dL)
Risk Level
Risk Category
?130 100-129
lt130lt100
Moderately High Risk

• ?2 Risk Factors
• 10-Year Risk 10-20

CHD or CHD Risk Equivalents10-Year Risk gt20  
High Risk
?100
lt100

• Established CVD Plus
• Multiple Major Risk Factors
• Severe and Poorly Controlled Risk Factors
• Multiple Risk Factors of the Metabolic Syndrome
• Acute Coronary Syndromes

Very High Risk
lt100 lt70
?100 lt100
When LDL-Clowering drug therapy is used, the
intensity of therapy should be sufficient to
achieve a 30-40 reduction in LDL-C
Therapeutic lifestyle changes (TLC) should be
initiated when LDL-C is at or above goal any
high-risk or moderately high-risk patient who has
lifestyle-related risk factors is a candidate for
TLC regardless of LDL-C level Optional LDL-C
goal Consider drug options.
Grundy et al. Circulation. 2004110227-239.