The recommendations for the management of dyslipidemia in the primary care setting are organized into 3 major algorithms. Each algorithm, the objectives and recommendations that accompany it, and the evidence supporting the recommendations are presented below. The quality of evidence (QE) grading (I-III); overall quality (Good, Fair, Poor); and final grade of recommendations (R) (A-D, I) are provided for specific statements. These grades, along with "net effect of the interventions" are defined at the end of the "Major Recommendations" field.
Screening Algorithm
Note: A list of all abbreviations is provided at the end of the "Major Recommendations" field.
- Adult Patient Enrolled in the Health Care System
Definition
This guideline addresses adults (age 17 years or older) eligible for care in the Veterans Health Administration/ Department of Defense (VHA/DoD) healthcare systems.
- Does Patient Have a History of Cardiovascular Disease (CVD)?
Objective
Identify patients who may benefit from lipid lowering therapy.
Recommendations
- All patients with known CVD are considered high-risk and should be treated with aggressive lipid-lowering therapy to prevent acute vascular events. These include, but are not limited to, acute myocardial infarction (AMI) or cerebrovascular accident (CVA).
- Does Patient Have Diabetes Mellitus?
Objective
Identify patients known to be at high-risk due to diabetes mellitus (DM).
Recommendation
- Patients with Type 2 DM are at significantly increased risk of CVD compared with non-diabetic patients of similar age and should, therefore, be treated more aggressively according to secondary prevention protocols. [A]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Persons with Type-2 DM, even in the absence of CVD, should be treated as CVD equivalent |
Haffner et al., 1998
Yusuf et al., 2000
Heart Protection Study Collaborative Group (HPS), 2002
Malmberg et al., 2000
|
I |
Good |
A |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Assess Risk Factors for Cardiovascular Disease
Objective
Identify clinical markers that predict an increased risk for developing CVD, thereby changing the interpretation of low-density lipoprotein (LDL) levels.
Recommendations
- Patients screened for dyslipidemia should be assessed for risk factors for CVD. Assessment should include, but not be limited to, the following:
- Age (males >age 45 and females >age 55)
- 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
- Current tobacco use/cigarette smoking (or within the last month)
- Hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg confirmed on more than one occasion, or current therapy with anti-hypertensive medications)
- Diabetes mellitus (DM) (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)
- Level of high-density lipoprotein cholesterol (HDL-C) (less than 40 mg/dL confirmed on more than one occasion).
- In obese patients (body mass index [BMI] >30), waist circumference measurement should be obtained to assist in the diagnosis of metabolic syndrome.
- Lipid Screening Criteria
Objective
Appropriately target individuals for lipid profile screening.
Lipid Screening Criteria |
- Male age 35 or older OR female age 45 or older OR
- Young adults with more than one of the following:
- Family history of premature CVD
- Patient is smoking
- Patient has or is being treated for hypertension
- Consider obtaining lipid profile for young adults with abdominal obesity
|
Recommendations
- 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]
- Fasting lipid profile testing should be obtained in individuals with a family history or clinical evidence of familial hyperlipidemia. [A]
- 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 [HTN]), or smoking. [B]
- 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]
- All persons with average or below average risk for atherosclerotic events should be screened for dyslipidemia every five years. [I]
- 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]
The 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 MI 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 (HTN, 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.
|
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Fasting lipid profile should be obtained in men >age 35 and women >age 45 |
Third Report of the National Cholesterol Education Program Expert Panel (NCEP) 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
|
I |
Good |
A |
2 |
Fasting lipid profile should be obtained in patients with family history or clinical evidence of familial hyperlipidemia |
NCEP ATP-III, 2002 |
I |
Good |
A |
3 |
Consider screening fasting lipid profile in young adults with other risk factors (family history of premature CVD, HTN, or smoking) |
NCEP ATP-III, 2002
Pignone et al., 2001
USPSTF, 2001
"A multicenter comparative trial," 1993
|
I |
Fair |
B |
4 |
Fasting lipid profile should be obtained for patients with increased waist circumference (men >40 inches , women >35 inches) to aid in assessment of metabolic syndrome |
NCEP ATP-III, 2002 |
I |
Good |
B |
5 |
Persons with average or below average CV risk should be screened every five years |
Working Group Consensus |
III |
Poor |
I |
6 |
Elderly patients age >75 should be screened if they have multiple CVD risk factors, a history of CVD and good quality of life with no other major life-limiting diseases |
Working Group Consensus |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Obtain a Fasting Lipid Profile
Objective
Screen appropriate patients for the presence of dyslipidemia.
Lipid Screening Test |
- Ensure test obtained in fasting state (9 to 14 hour fast)
- Total cholesterol (TC), triglycerides (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)
|
Recommendations
- A complete fasting lipid profile should be obtained in an individual with other risk factors for coronary disease. [A]
- 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]
- 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]
- Lipid profiles should not be measured in pregnant women until three to four months post partum. [I]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
A complete fasting lipid profile should be obtained in individuals with other risk factors for coronary artery disease (CAD) |
USPSTF, 2001 |
I |
Good |
A |
2 |
Clinical decisions should be based upon lipid profiles done 1 to 8 weeks apart (fasting or no fasting) with an LDL-C or TC difference of less than 30 mg/dL |
Working Group Consensus |
III |
Poor |
I |
3 |
Lipid profiles should not be obtained within 8 weeks post-acute hospitalization, surgery, trauma, or infection unless they are obtained within 12 to 24 hours of the event to ensure accuracy |
Working Group Consensus |
III |
Poor |
I |
4 |
Lipid profiles should not be measured in pregnant women until three to four months post partum |
Working Group Consensus |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- TG >400 mg/dL, Apply Diet and Exercise to Reduce TG; Consider Direct Measurement of LDL-C
Objective
Identify patients whose LDL-C is confounded by secondary/modifiable causes of hypertriglyceridemia.
Recommendations
- If TG levels can be brought to <400 mg/dL by dietary or other interventions, then Friedewald's formula can be used to calculate a more exact LDL-C level. [C]
- If TGs cannot be brought to levels less than 400 mg/dL, then consider measuring LDL-C directly, or estimate the LDL-C using the following equation: [I]
Estimated LDL-C = (TC – HDL) – 30
- Screen and treat common causes of elevated TGs: fatty diet, high carbohydrate diets, alcohol use, hypothyroidism, and hyperglycemia. [B]
- In the absence of secondary causes, the first-line therapy for elevated TGs should be therapeutic life-style changes. [C]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Use Friedewald's formula to calculate LDL-C – when TG levels can be brought to <400 mg/dL by dietary or other interventions |
Friedewald et al., 1972
NCEP ATP-III, 2002
|
III |
Fair |
C |
2 |
If TGs are >400 consider directly measuring LDL-C |
Friedewald et al., 1972
NCEP ATP-III, 2002
Stone & Blum, 2002
|
III |
Poor |
I |
3 |
Screen and treat common causes of elevated TGs |
Cleeman, 1998
Friedewald et al., 1972
NCEP ATP-III, 2002
Stone & Blum, 2002
|
II-3 |
Fair |
B |
4 |
In the absence of secondary causes, the first-line therapy for elevated TGs should be therapeutic life-style changes |
Cleeman, 1998
Friedewald et al., 1972
NCEP ATP-III, 2002
Stone & Blum, 2002
|
II-3 |
Poor |
C |
QE = Quality of Evidence R = Strength of Recommendation (see Appendix A in the original guideline document)
- Is Lipid Profile Abnormal?
Objective
Identify patients who require further evaluation and/or therapy for dyslipidemia.
Classification of Serum Lipids |
Total Cholesterol (TC) mg/dL (mmol/L) |
Category |
<200 (<5.2)
200 to 239 (5.2 to 6.1)
>240 (> 6.2)
|
Normal
Borderline high
High
|
LDL-Cholesterol mg/dL (mmol/L) |
<100 (<2.6)
100 to 129 (2.6 to 3.3)
130 to 159 (3.4 to 4.0)
160 to 189 (4.1 to 4.8)
>190 (>4.9)
|
Normal
Above, near optimal
Borderline high
High
Very high
|
HDL- Cholesterol mg/dL (mmol/L) |
<40 (<1.0)
>60 (>1.6)
|
Low
High
|
Triglycerides (TG) mg/dL (mmol/L) |
<150 mg/dL (<1.7)
150 to 199 mg/dL (1.7 to 2.2)
200 to 499 mg/dL (2.3 to 5.6)
>500 mg/dL (>5.6)
|
Normal
Borderline High
High
Very High
|
Recommendation
- Patients with LDL >130 mg/dL, HDL <40 mg/dL, or TG >200 mg/dL should be assessed for further management of dyslipidemia. [C]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Classify Serum Lipid levels based on degree of elevation of LDL, TG, or low HDL |
NCEP ATP-III, 2002 |
II-2 |
Good |
C |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Encourage Healthy Lifestyle
Objective
Promote lifestyle changes that will decrease the risk of CVD.
Recommendations
- All adults should be encouraged to adopt healthy lifestyles that may reduce the risk of cardiovascular disease, to include:
- Tobacco cessation interventions offered to all smokers [A]
- Eat a healthy diet [B]
- Engage in 30 minutes or more of moderate intensity physical activity on most days of the week. [B]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Advise patients to stop smoking |
Fiore et al., 2000
Silagy & Stead, 2001
|
I |
Good |
C |
2 |
Provide tobacco cessation interventions to smokers |
Fiore et al., 2000 |
I |
Good |
A |
3 |
Provide interventions to encourage a healthy diet |
Beresford et al., 1997
McCarron et al., 1997
|
I |
Fair |
B |
4 |
Encourage 30 minutes or more of moderate intensity aerobic physical activity on most days of the week |
Pate et al., 1995
American College of Sports Medicine (ACSM), 1995
Pollock & Wilmore, 1990
Spate-Douglas & Keyser., 1999
|
I
IIa |
Fair |
B |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Repeat Dyslipidemia Evaluation in 1 to 5 Years
Objective
Provide appropriate clinical follow-up for patients initially at low-risk for CVD.
Recommendations
- Patients with average or below average risk for atherosclerotic events should be screened for dyslipidemia every five years. [B]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Patients with average or below average risk for atherosclerotic events should be screened for dyslipidemia every five-year period |
NCEP ATP-III, 2002
"A multicenter comparative trial," 1993
|
III |
Fair |
B |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
Initiation of Therapy Algorithm
- Patient with Abnormal Lipid Profile or History of CVD or Diabetes
Patients managed by this guideline algorithm have abnormal lipid profiles (dyslipidemia) or evidence of cardiovascular disease (CVD) or diabetes.
L1. Obtain History, Physical Examination, and Laboratory Tests. Assess for Secondary Causes, Familial Disorders, and Comorbidities
Objective
Detect and if needed treat health disorders that present with an elevated LDL-C or TG, low HDL-C, or metabolic syndrome.
Recommendations
- Adults with abnormal lipid profiles (dyslipidemia) should be assessed for secondary causes, familial disorders, and other underlying conditions that may influence lipid levels. [I]
- Assessment for secondary causes should be based on medical history, physical examination and laboratory tests:
- Measurement of serum thyroid-stimulating hormone (TSH), blood urea nitrogen (BUN)/creatinine, liver function tests (LFTs), and a dipstick urinalysis should be obtained to exclude hypothyroidism, chronic renal failure, obstructive liver disease, and nephrotic syndrome conditions. [I]
- If dipstick urine protein is >1+ (detected in two urine tests), nephrotic syndrome as a secondary cause of elevated LDL-C should be ruled out. [I]
- Serum lipids should be assayed six to eight weeks post-TSH normalization to determine the need for additional treatment. [I]
- Patients with hypertriglyceridemia should be evaluated for alcohol use, diabetes, and hypothyroidism. Addressing these underlying conditions can improve or normalize triglyceride levels, and failure to address these can render therapy ineffective. [I]
- Lipid levels in patients treated for secondary hyperlipidemia should be repeated six to eight weeks post correction of the underlying disorder.
- Family members of patients presenting with very severe hypercholesterolemia should be screened to detect other candidates for therapy.
- Consider consulting with a specialist to assist the primary care clinician in co-managing patients with familial disorders who do not respond to therapy. [I]
Secondary Causes of Lipid Abnormalities |
Disorder/Patient Characteristic |
Effect on Lipids |
Laboratory Test for Diagnosis |
Chronic renal failure/postrenal transplantation |
Increase TG
Increase TC
Decrease HDL-C
|
SCr |
DM |
Increase TG
Increase TC
Decrease HDL-C
|
Glucose, HbA1c |
Ethanol use |
Increase TG
Increase HDL-C
|
-- |
HIV/AIDS Wasting |
Increase TG
Decrease TC
Decrease HDL-C
Decrease LDL-C
|
-- |
HIV/AIDS (HAART) |
Increase TG
Increase TC
Increase HDL-C
|
-- |
Hypothyroidism |
Increase TG
Increase TC
Increase LDL-C
|
TSH |
Inactivity |
Decrease HDL-C |
-- |
Nephrotic syndrome |
Increase TC
Increase LDL-C
|
Urinalysis, serum albumin |
Obesity |
Increase TG
Decrease HDL-C
|
-- |
Obstructive liver disease |
Increase TC |
LFTs (Alkaline phosphatase, total bilirubin) |
Estrogen therapy |
Increase TG
Decrease LDL
Increase HDL
|
-- |
Medications |
Variable |
-- |
AIDS = acquired immune deficiency syndrome; DM = diabetes mellitus; HAART = highly active antiretroviral therapy; HbA1c = glycosylated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HIV = human immunodeficiency virus; LDL-C = low-density lipoprotein cholesterol; LFTs = liver function tests; SCr = serum creatinine; TC = total cholesterol; TG = triglycerides; TSH = thyroid-stimulating hormone
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Detect and treat secondary cause of dyslipidemia |
NCEP ATP-III, 2002
Stone et al., 1997
Stone & Blum, 2002
|
III |
Poor |
I |
2 |
Refer familial hypercholesteremia to specialist |
Working Group Consensus |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
L2. Obtain Baseline Serum Transaminase (ALT/AST) Prior to Starting Lipid Lowering Therapy
Objective
Establish baseline transaminase monitoring parameters prior to initiating lipid lowering therapy.
Recommendations
- Baseline serum transaminase (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) should be obtained prior to starting lipid-lowering therapy. [I]
- Levels of serum transaminase (ALT/AST) should be obtained in patients on statin, 6 to 12 weeks after starting statin therapy, and/or change in dose or combination therapy, then annually or more frequently, if indicated. [I]
- Levels of serum transaminase (ALT/AST) should be obtained in patients on niacin, 6 to 12 weeks after reaching a daily dose of 1,500 mg and 6 to 12 weeks after reaching the maximum daily dose, then annually or more frequently, if indicated. [I]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Statins—
Evaluate ALT/AST initially, approximately 6 to 12 weeks after starting, then annually or more frequently, if indicated |
NCEP ATP-III, 2002 |
III |
Poor |
I |
2 |
Nicotinic Acid—
Evaluate ALT/AST initially, 6 to 12 weeks after reaching a daily dose of 1,500 mg, 6 to 12 weeks after reaching the maximum daily dose, then annually or more frequently, if indicated |
NCEP ATP-III, 2002 |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
M1. History of Acute Coronary Syndrome in Past 6 Months?
Objective
Identify patients with recent acute coronary syndrome (ACS) for whom there is a compelling need for statin therapy regardless of current lipid levels.
Recommendations
- A lipid panel should be drawn at the time of admission for all patients with suspected acute coronary syndrome (ACS). [C]
- Initiating a moderate- to high-dose statin therapy prior to hospital discharge may be considered in patients admitted with ACS irrespective of their lipid profile. [B]
- Patients with recent ACS (within the past 6 months) should be on a moderate dose of statin therapy to reduce LDL-C level below 100 mg/dL. [A]
- A lower target (70 mg/dL) may be considered for very high-risk patients. [B]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
For patients admitted with ACS, a lipid panel should be drawn at the time of admission |
Working Group Consensus |
III |
Poor |
I
|
2 |
Patients should be started on moderate- to high-dose statins prior to hospital discharge and irrespective of their lipid profile |
Bybee et al., 2002
Lorenz et al., 2005
Stenestrand & Wallentin, 2001
|
I |
Good |
B |
3 |
If not started on a statin prior to hospital discharge, then one should be started within 6 months post-ACS |
de Lemos et al., 2004
Cannon et al., 2004
|
I |
Good |
A |
4 |
An optional lower target for LDL-C may be considered for post-ACS patients |
Cannon et al., 2004 |
I |
Good |
B |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
M2. History of CVD or DM and LDL-C Above Goal?
(See Screening Algorithm, Annotations B and C)
M3. Calculate 10-Year Risk Score for CVD
Objective
Determine short-term risk (i.e., over ten years) as the basis for determining the type and intensity of interventions.
Recommendations
- A global 10-year risk for CVD should be calculated to assess the short-term (10-year) absolute risk of a CVD event. [A]
- The Framingham Risk Calculator should be used, as it is the most commonly used and readily available calculator validated in numerous populations. [I]
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]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
A global 10-year risk for CVD should be calculated to assess the short-term (10 years) absolute risk of a CVD event |
Grover, Coupal, & Hu, 1995
Grover et al., 2000
Grundy et al., 2004
|
I |
Good |
A |
2 |
The Framingham Risk Calculator is the most commonly used and readily available calculator validated in numerous populations |
Grundy et al., 1999
Sheridan, Pignone, & Mulrow, 2003
Wilson et al., 1998
|
III |
Poor |
I |
3 |
Other risk markers or measures of atherosclerotic burden may be useful to adjust the risk category |
Ford et al., 1998
Greenland et al., 2000; 2004
O'Donnel, 2004
Pearson et al., 2003
Pletcher et al., 2004
Ridker, 2001
|
III |
Fair |
C |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Determine Risk for CVD and Establish the Goal for Interventions
Recommendations
- Goals of lipid lowering therapy should be tailored to risk level and based upon the balance between benefits, risks, and patient preferences. [C]
Goals of Therapy for Secondary Prevention
- LDL-C should be lowered to <100 mg/dL for patients with a recent ACS. [A]
- An optional lower target for LDL-C (<70 mg/dL) may be considered for very high-risk post-ACS patients. [B]
- LDL-C should be lowered to <100 mg/dL for patients with previous documented CHD or CVD equivalent (DM with other major risk factors) for secondary prevention. [A]
- LDL-C should be lowered to <130 mg/dL for patients with DM without other major risk factors for secondary prevention. [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]
- LDL-C should be lowered to <130 mg/dL for patients with intermediate 10-year risk (15 to 20 percent). [B]
- LDL-C should be lowered to <130 mg/dL for patients with intermediate 10-year risk (10 to 14 percent). [C]
- LDL-C should be lowered to <160 mg/dL for patients with low 10-year risk. [I]
- 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.
Table. Goals of Lipid Lowering Therapy
|
Risk Category |
Number of Risk Factors (RF) |
10-Year Risk |
LDL-C Goal
mg/dL * |
Remarks |
1 |
Recent ACS |
N/A |
N/A |
<100 |
Option <70 mg/dL |
2 |
CHD or equivalent (DM with other risk factors) |
N/A |
N/A |
<100 |
Optional <130 for DM with no other risk factors |
3 |
High |
2 + RF |
>20% |
<100 |
-- |
4 |
Intermediate |
2 +RF |
15 to 20% |
<130 |
-- |
5 |
10 to 14% ** |
<130 |
-- |
6 |
Low |
0-1 RF |
N/A |
<160 |
-- |
N/A = Not applicable
* Recommendations are based on quality of evidence for improving CVD outcomes.
** There is insufficient evidence at this time to recommend routine screening for other risk markers not included in the risk index (e.g., FH, high sensitive C-reactive protein [hsCRP], metabolic syndrome, depression), or evidence of significant atherosclerotic burden (e.g., high coronary artery calcification scores, intima medial thickness, abnormal brachial reactivity, or abnormal ankle-brachial index). These risk markers have independent prognostic value whereby abnormal values can shift risk percent upward across treatment thresholds with more robust evidence for efficacy. Therefore, they may be useful in the intermediate risk patient for whom it is less convincing that drug therapy would have a meaningful impact on outcomes. Example: Patient with a 10-year risk of 13 percent in whom an abnormal test with a proven adjusted relative risk of >2 would shift the patient to a high-risk category (across a 20 percent, 10-year risk threshold).
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Target lipid lowering therapy to risk |
"27th Bethesda Conference," 1996
Grundy et al., 2004
|
I |
Good |
C |
|
Secondary Prevention |
2 |
Goal <100 mg/dL for recent ACS patients |
Schwartz et al., 2001
Cannon et al., 2004
Nissen et al., 2004
|
I |
Good |
A |
3 |
An optional lower target for LDL-C may be considered for severe post-ACS patients |
Cannon et al., 2004 |
I |
Good |
B |
4 |
Goal <100 mg/dL for patients with previous documented CHD or CVD or CVD equivalent = DM |
Sacks et al., 1996
Heart Protection Study Collaborative Group, 2002
LaRosa, He, & Vupputuri, 2005
|
I |
Good |
A |
5 |
Goal <130 mg/dL for patients with DM without other major risk factors |
Haffner et al., 1998
NCEP Consensus
|
III |
Poor |
C |
|
Primary Prevention |
6 |
Goal <100 mg/dL for high-risk group |
Sever et al., 2003
Heart Protection Study Collaborative Group, 2002
"Screening experience and baseline characteristic in the West of Scotland Coronary Prevention Study," 1995
|
I |
Fair |
B |
7 |
Goal <130 mg/dL for patients with intermediate 10-year risk (15 to 20%) |
Downs et al., 1998 |
I |
Fair |
B |
8 |
Goal <130 mg/dL for intermediate-risk group 10 to 14% |
NCEP ATP-III, 2002 |
III |
Poor |
C |
9 |
Goal <160 mg/dL for low-risk group |
Consensus Group |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Initiate Lipid Lowering Therapy to Achieve Goal
Objective
Select an appropriate therapy based on LDL-C baseline level and other risk factors for CVD.
Recommendations
Non-Pharmacologic Therapy
- Therapeutic lifestyle changes (TLC) should be recommended for ALL patients with dyslipidemia, regardless of risk or baseline LDL-C level. [C]
Drug Therapy for Secondary Prevention
- All patients with a recent ACS should be on at least a moderate dose of statin therapy. [A]
- Statin drug therapy should be initiated for patients with previous documented CHD or CVD equivalent (diabetes with other major risk factors) if baseline LDL-C is >100 mg/dL. [A]
- Statin drug therapy should be initiated for patients with documented DM with no major risk factors if baseline LDL-C is >130 mg/dL. [C]
- Statin drug therapy may be considered optional for all patients with CHD or CVD equivalent (diabetes with other major risk factors) regardless of LDL-C baseline. [B]
Drug Therapy for Primary Prevention
- Drug therapy should be initiated for high-risk patients (>20%) if baseline LDL is >130 mg/dL. [B]
- Drug therapy is optional to consider in high-risk patients (>20%) if baseline LDL is 100 to 129 mg/dL. [B]
- Drug therapy may be offered to patients with high-intermediate risk (15 to 20 percent) if baseline LDL is >130 mg/dL. [B]
- Drug therapy may be offered to patients with low-intermediate risk (10 to 14 percent) if baseline LDL is >160 mg/dL. [C]
- Drug therapy may be offered to low-risk patients (<10 percent) if baseline LDL is >190 mg/dL. [I]
The following table summarizes the lipid lowering strategy for patients in primary prevention. Individual management of cardiovascular risk should be informed mainly by the probable absolute magnitude of treatment benefits. Lowering absolute risk involves modification of multiple risk factors/co-morbidities, not only LDL-C levels. Therefore, these goals should serve as a general guide and clinical judgment should be used to modify the goals as appropriate for each patient.
Table. Dyslipidemia Therapy Thresholds and Goals
|
Risk Category |
Disease Status or Risk Factors |
Calculated 10-Year Risk |
TLC |
LDL-C Level for Considering Statin Drug Therapy |
LDL Goal of Therapy |
Secondary
Prevention |
Very high |
Recent ACS |
N/A |
All |
All |
<100 mg/dL
<70 optional
|
CHD or DM with other risk factors |
N/A |
All |
>100 mg/dL |
<100 mg/dL |
DM with no other risk factors |
N/A |
All |
>130 mg/dL
100 to 129 optional
|
<130 mg/dL |
Primary
Prevention |
High |
More than 2 RF |
>20% |
All |
>130 (or HDL <40)
100 to 129 optional
|
<100 mg/dL |
Intermediate |
More than 2 RF |
15 to 20% |
All |
>130 mg/dL |
<130 mg/dL |
10 to 14% * |
All |
>160 mg/dL |
<130 mg/dL |
Low |
0 or 1 RF |
N/A |
All |
>190 mg/dL |
<160 mg/dL |
LDL-C reduction of 30-40 percent from baseline may be considered an alternative therapeutic strategy for patients who cannot meet the above goals.
N/A = Not applicable; TLC = Therapeutic Lifestyle Changes; RF = Risk Factor
* There is insufficient evidence at this time to recommend routine screening for other risk markers not included in the risk index (e.g., FH, hsCRP, metabolic syndrome, depression), or evidence of significant atherosclerotic burden (e.g., high coronary artery calcification scores, intima medial thickness, abnormal brachial reactivity, or abnormal ankle-brachial index). These risk markers may be useful in the intermediate risk patient for whom it is less convincing that drug therapy would have a meaningful impact on outcomes.
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Therapeutic lifestyle changes should be recommended for ALL patients |
NCEP ATP-III, 2002 |
III |
Fair |
C |
2 |
For recent ACS patients, moderate to high-dose statins should be given prior to hospital discharge; If not started prior to discharge, then statin therapy should be started within 6 months post ACS |
de Lemos et al., 2004
Schwartz et al., 2001
Cannon et al., 2004
|
I |
Good |
A |
3 |
Initiate drug therapy in all patients with previous documented CHD or CVD equivalent (DM with other major risk factors) if baseline LDL-C is >100 mg/dL |
Sacks et al., 1996
"Randomised trial," 1994
Heart Protection Study Collaborative Group 2002
"Prevention of cardiovascular events," 1998
Shepherd et al., 2002
LaRosa, He, & Vupputuri, 2005
|
I |
Good |
A |
4 |
Drug therapy should be initiated for patients with DM and NO major risk factors) if baseline LDL-C is >130 mg/dL |
NCEP Consensus of Experts |
III |
Poor |
C |
5 |
Drug therapy may be considered for all patients with DM and other risk factors regardless of LDL baseline |
Colhoun et al., 2004
LaRosa, He, & Vupputuri, 2005
|
I |
Fair |
B |
6 |
Drug therapy should be initiated for high-risk patients (10-year risk >20%) if baseline LDL is >130 mg/dL |
Downs et al., 1998
Sever et al., 2003
"Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study", 1995
|
I |
Good |
A |
7 |
Consider drug therapy in high-risk patients if baseline LDL is 100 to 129 mg/dL |
Heart Protection Study Collaborative Group, 2002 |
I |
Fair |
B |
8 |
Offer drug therapy for high-and intermediate-risk (15 to 20%) if baseline LDL is >130 mg/dL |
Sever et al., 2003
Downs et al., 1998
"Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study," 1995
|
I |
Fair |
B |
9 |
Offer drug therapy for low-intermediate risk (10-15%) patients if baseline LDL is >160 |
NCEP ATP-III, 2002 |
III |
Poor |
C |
10 |
Offer drug therapy for low-risk patients (<10%) if baseline LDL is >190 mg/dL |
NCEP ATP-III, 2002 |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Therapeutic Lifestyle Change (TLC)
For secondary prevention of recurrent CVD events, non-pharmacologic therapy is always indicated, but should not delay appropriate pharmacotherapy.
For primary prevention of CVD, emphasis on TLC is an important component and is effective in reducing CVD risk by lowering LDL-C and blood pressure. Ample time should be given (3 to 6 months) for patients to improve their LDL-C and total lipid profile prior to starting lipid-lowering medication. Patients failing primary clinician efforts may benefit from medical nutrition therapy (MNT) provided by a registered dietician or other qualified nutritionist (see Appendix C, Medical Nutrition Therapy in the original guideline document).
TLC is provided in a step-wise approach focused on initiating TLC components and followed by subsequent evaluation of the effect on LDL-C and moving to intensify MNT as indicated. See Figure 2 "Step Wise Care Approach" in the original guideline document.
P1. Medical Nutrition Therapy
Objective
Improve dyslipidemia using medical nutrition therapy (MNT).
Recommendations
- Diet intervention should be the first step in lipid lowering therapy. [B]
- Patients whose initial treatment is TLC should be given 3 to 6 months of dietary therapy prior to beginning medication and longer, if lipids are improving and nearing LDL thresholds. [B]
- Initial diet should focus on reduction of saturated fats to <7 percent of total calories and dietary cholesterol to <200 mg/day similar in composition to the TLC diet (formerly Step II diet). [B]
- The range of 25 to 35 percent of total calories from fat is to be paired with keeping saturated fats and trans-fatty acid percents of total calories low.
- Advise 10 percent monounsaturated fat, <7 percent saturated fat, <200 mg cholesterol diet.
- If TGs are elevated, ensure that blood glucose is under control, limit alcohol and simple sugars, and evaluate need for weight loss. Emphasis should be placed on weight reduction and physical activity.
- Limit foods with trans fatty acids (e.g., stick margarine, shortening, and commercially baked products and processed food).
- Select >5 to 6 servings/day fruits and vegetables and six servings/day whole-grain products.
- Patient's specific diet should be individualized based on nutrition assessment, other CVD risk factors, other disease conditions, and patient's lifestyle. [I]
- Patients should be evaluated 4 to 6 weeks after their initial consultation. A lipid profile and anthropometric data should be analyzed. Further dietary intervention may include:
- Increase soluble (viscous) fiber to 10 to 25 g/day to lower LDL-C. [B]
- Increase plant sterols/stanols to 2 g/day to lower LDL-C. [B]
- Include nuts such as walnuts and almonds (1 oz. ~5 times/week) and soy protein (25 g/day or 8 oz. of tofu) to lower LDL-C. [B]
- Select fatty fish (average of 7 oz./week) (fish oil) to lower TG. [B]
- Weight management for overweight and obese patients should be encouraged to lower LDL-C and TG and to reduce CV risk. [B]
- Patients in whom triglycerides >500 mg/dL should receive strict diet therapy including avoidance of alcohol, restriction of dietary fat, and avoidance of concentrated carbohydrates (sweets). For triglycerides >1000 mg/dL a very low fat diet should be instituted quickly to reduce chylomicronemia and risk of acute pancreatitis.
- Patients with evidence of metabolic syndrome should receive MNT that incorporates the additional protocol for weight management with increased physical activity. [B]
Table. Essential Components of Therapeutic Lifestyle Changes (TLC) |
Component |
Recommendation |
LDL-raising nutrients
Saturated fats*
|
Less than 7% of total calories |
Dietary cholesterol |
Less than 200 mg/day |
Therapeutic options for LDL lowering |
Plant stanols/sterols |
2 grams per day |
Increased viscous (soluble) fiber |
10 to 25 grams per day |
Total calories (energy) |
Adjust total caloric intake to maintain desirable body weight/prevent weight gain |
Physical activity |
Include enough moderate exercise to expend at least 200 kcal per day |
*Trans fatty acids are another LDL-raising fat that should be kept at a low intake. |
Table. 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 to 35% of total calories* |
Carbohydrate** |
50 to 60% of total calories* |
Dietary fiber |
20 to 30 grams per day |
Protein |
Approximately 15% of total calories |
*ATP-III allows an increase of total fat to 35 percent of total calories and a reduction in carbohydrates to 50 percent 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.
|
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Use MNT for lowering LDL-C. |
Delahanty et al., 2001; 2002
Sikand et al., 2000
Yu-Poth et al., 1999
|
I |
Good |
B |
2 |
Recommend 3 to 6 months of diet therapy prior to pharmacotherapy, if needed |
NCEP ATP-III, 2002 |
I |
Fair |
B |
3 |
Recommend a low saturated fat, low cholesterol diet |
NCEP ATP-III, 2002 |
II |
Good |
B |
4 |
Reduce saturated fats to less than 7% of total calories |
Hooper et al., 2001
Krauss et al., 2000
Lichtenstein et al., 2002
NCEP, 2001
|
I |
Fair |
B |
5 |
Provide individualized dietary counseling with reinforcement during follow-up |
NCEP ATP-III, 2002
Tang et al., 1998
|
I |
Fair |
B |
6 |
Consume viscous fiber (at least 10-25 grams/day) |
Brown et al., 1999
Kris-Etherton et al., "High-soluble fiber food," 2002
|
I |
Fair |
B |
Eat plant sterols/stanol esters (2 to 3 g/day) |
Christiansen et al., 2001
Jenkins et al., 2003; 2005
Lichtenstein & Deckelbaum, 2001
Maki et al., 2001
|
I |
Fair |
B |
Eat 5 ounces of nuts per week |
Jenkins et al., 2003
Krauss et al., 2000
Lovejoy et al., 2002
Sabate, 2003
|
I |
Fair |
B |
Eat 25 grams/day of soy protein |
Anderson, Johnstone, & Cook-Newell, 1995
Erdman, 2000
Merritt, 2004
Meyer et al., 2004
|
I |
Fair |
B |
Eat at least two servings of fish per week |
Kris-Etherton, "Fish consumption," 2002
NCEP ATP-III, 2002
|
I |
Fair |
B |
7 |
Reduce caloric intake and increase physical activity to maintain desirable body weight |
Krauss et al., 2000
NCEP ATP-III, 2002
|
I |
Fair |
B |
8 |
Low fat diet for TGs >500 mg/dL;
Very low fat diet if TGs >1000 mg/dL
|
American Dietetic Association (ADA), 2001
NCEP ATP-III, 2002
|
I |
Fair |
B |
9 |
Recommend MNT for management of metabolic syndrome |
ADA, 2001
NCEP ATP-III, 2002
Nieman et al., 2002
Sartorio et al., 2003
|
I |
Fair |
B |
QE = Quality of Evidence; Strength of Recommendation (see Appendix A in the original guideline document)
P2. Physical Activity/Exercise and Weight Control
Recommendations
- Moderate intensity levels of physical activity should be performed for at least 30 minutes most, preferably all, days of the week. [B]
- In patients with CVD, aerobic exercise should not precipitate angina.
- Increased physical activity through lifestyle change should be encouraged, as it is equally as effective as structured exercise in reducing body fat, improving cardiorespiratory fitness, and improving cardiovascular risk factors. [B]
- Physical activity, through lifestyle change or structured exercise, should be encouraged to maintain weight control (or weight loss if overweight or obese), to improve insulin resistance, and increase HDL-C. [B]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Increase physical activity to improve lipid profile |
Fahlman et al., 2002
Halbert et al., 1999
Kraus et al., 2002
Stefanick et al., 1998
|
I |
Fair |
B |
2 |
Engage in moderate levels of exercise/physical activity for at least 30 minutes, on most days of the week |
ACSM 2002
Pate et al., 1995
U.S. DHHS, 1996
|
I |
Fair |
B |
3 |
Increased physical activity is just as effective as structured exercise in reducing body fat, improving cardiorespiratory fitness |
Lee et al., 2001
Manson et al., 1999; 2002
Wannamethee, Shaper, & Walker, 2000
|
II |
Fair |
B |
4 |
Exercise should be encouraged to maintain weight control (or weight loss if overweight or obese) |
National Heart Lung, and Blood Institute (NHLBI), 1998
Scranton et al., 2004
|
II |
Fair |
B |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
Q1. Pharmacotherapy: Monotherapy
Objective
Reduce the risk of CVD events and achieve lipid goals through the use of optimal pharmacotherapy.
Recommendations
- Pharmacologic treatment of dyslipidemia should be individualized and dictated by lipid levels. [B]
Elevated LDL-C
- Statins are first line agents in primary and secondary prevention of CVD regardless of HDL-C or TG level. [A]
- Moderate doses of formulary statins (to achieve an LDL-C reduction of 25 percent or greater) should be initiated unless a patient is considered to be at greater than usual risk for adverse events from statins (e.g., myopathy). [A]
- For patients who cannot tolerate statins, niacin or resins should be considered for treatment. [A]
- There is insufficient clinical outcome evidence to recommend ezetimibe monotherapy for reduction of CV risk. [I]
- Ezetimibe can be considered for lowering LDL-C in patients who are unable to tolerate other lipid-lowering drugs. [A]
- The dose of statin should be adjusted at 6 to 12 week intervals until individual LDL-C goals are achieved or statin doses have been maximized. [I]
Isolated Hypertriglyceridemia
- Niacin, fibrates, or fish oil supplements may be used in treatment of hypertriglyceridemia. [B]
Isolated Low HDL-C
- For secondary prevention, gemfibrozil or niacin may be used in patients with isolated low HDL-C and normal LDL-C. [A-Gemfibrozil; B-Niacin]
Safety and Follow-Up
- Patients treated with statins or fibrates should be educated regarding the importance of recognizing and reporting any unexplained muscle tenderness, pain, or weakness. [I]
- Lipid profiles should be repeated 6-12 weeks after initiation of therapy and/or change in dose and/or combination therapy. [B]
- Liver function tests (LFTs) should be performed prior to and after 12 weeks following initiation of treatment, any elevation in dose, and periodically thereafter in those receiving statins, fibrates, or niacin. [I]
- Creatine kinase (CK) levels should be obtained in patients who develop muscle pain, weakness, or tenderness after institution of statin or fibrate therapy. [I]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Pharmacologic treatment of dyslipidemia should be individualized and is dictated by lipid levels |
NCEP ATP-III, 2002 |
I |
Fair |
B |
2 |
Statins are first line agents in primary and secondary prevention regardless of baseline TG or HDL-C level |
Primary Prevention:
Downs et al, 1998
Sever et al., 2003
Colhoun et al., 2004
"Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study," 1995
Secondary Prevention:
Sacks et al., 1996
4S, 1994
Heart Protection Study Collaborative Group, 2002
"Prevention of cardiovascular events," 1998
Shepherd et al., 2002
|
I |
Good |
A |
3 |
Moderate doses of formulary statins (to achieve an LDL-C reduction of 25% or greater) should be initiated (unless greater than usual risk for adverse events) |
Primary Prevention:
Downs et al., 1998
"Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study," 1995
Secondary Prevention:
Sacks et al., 1996
4S, 1994
Heart Protection Study Collaborative Group, 2002
"Prevention of cardiovascular events," 1998
Serruys et al., 2002
Shepherd et al., 2002
Cannon et al., 2004
|
I |
Good |
A |
4 |
Consider treatment with other lipid lowering agents (niacin or resins) for patients who cannot tolerate statins |
Primary Prevention:
Frick et al., 1993
Lipid Research Clinics Program–Coronary Primary Prevention Trial (LRC-CPPT), 1984
Secondary Prevention:
"Clofibrate and niacin in coronary heart disease," 1975
Jamshidi et al., 2002
Robins, Collins, & Rubins, 1999
|
I |
Good |
A |
5 |
Use of ezetimibe monotherapy for preventing CVD |
Working Group Consensus |
III |
Poor |
I |
6 |
Ezetimibe can be considered for lowering LDL-C in patients who are unable to tolerate other lipid-lowering drugs |
Bays et al., 2001
Knopp et al., "Evaluation of the efficacy," 2003
Knopp et al., "Effects of ezetimibe," 2003
Sudhop et al., 2002
|
I |
Good |
A |
7 |
Aggressive early treatment with a moderate dose of statins for all patients with recent ACS |
Cannon et al., 2004
Nissen et al., 2004
|
I |
Good |
A |
8 |
Dose of statin should be adjusted at 6 to 12 week intervals until individual LDL-C goals are achieved or statin doses have been maximized |
Working Group Consensus |
III |
Poor |
I |
Isolated Hypertriglyceridemia |
9 |
Consider niacin, fibrates, or fish oil supplements to lower TGs |
Niacin
NCEP ATP-III, 2002
Fibrates
NCEP ATP-III, 2002
Fish Oils
Harris 1997
Farmer et al., 2001
|
I |
Fair |
B |
Isolated Low HDL-C |
10 |
Gemfibrozil |
Robins, Collins, & Rubins, 1999 |
I |
Good |
A |
11 |
Niacin to increase HDL-C |
King et al., 1994
Lavie, Mailander, & Milani, 1992
Miller et al.,1993; 1995
Vega & Grundy, 1989
|
I |
Fair |
B |
Safety and Follow-Up |
12 |
Provide patients with education about unexplained muscle tenderness, pain, or weakness |
NCEP ATP-III, 2002 |
III |
Poor |
I |
13 |
Repeat lipid profile in 6-12 weeks after initiation of therapy and/or change in dose and/or with combination therapy |
Benner et al., 2004
NCEP ATP-III, 2002
|
II |
Fair |
B |
14 |
LFT should be performed prior to and after 6-12 weeks following initiation/change of dose, and periodically thereafter in those receiving statins, fibrates, or niacin |
NCEP ATP-III, 2002 |
III |
Poor |
I |
15 |
Obtain CK levels in patients who develop muscle pain, weakness, or tenderness after institution of statin or fibrate therapy |
NCEP ATP-III, 2002 |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
Q2. Pharmacotherapy: Combination Therapy
Objective
Achieve lipid goals through the use of combination pharmacologic agents.
Recommendations
LDL-C Lowering Combination Therapy [ONLY FOR SECONDARY PREVENTION]
- For patients not at goal, monotherapy should be titrated until goal is achieved or maximum tolerable dose has been reached. [C]
- Combination therapy to achieve LDL-C goal may be considered for carefully selected patients who do not achieve the LDL-C goal with maximally tolerated monotherapy. [I]
- Combination lipid-lowering therapy should include a statin unless the patient is unable to tolerate statins. [A]
- Addition of a resin to the statin can be considered for secondary prevention in patients not meeting their LDL-C goals on maximally tolerated doses of statins. [B]
- Addition of niacin or a resin to the statin can be considered in patients not meeting their LDL-C goals to further reduce the LDL-C level. [B]
- Addition of ezetimibe to the statin can be considered in patients not meeting their LDL-C goals on maximally tolerated doses of statins and unable to tolerate niacin or a resin to reduce the LCL-C level. [I]
- In patients unable to tolerate statins and not achieving their LDL-C goals with niacin or resins, a combination of both resin and niacin may be considered. [B]
- In any combination therapy the lowest possible dose of statin should be used to achieve lipid goals. When combined with fibrates (greatest risk), niacin, or possibly ezetimibe, the risk of adverse events with statins (e.g., muscle toxicity) appears to increase with increasing statin doses. [C]
Elevated LDL-C and Very High Triglycerides (>500 mg/dL)
If non-HDL goals cannot be achieved with a statin (or other LDL-lowering regimen) alone, a TG-lowering drug may be added to the statin. Choices are niacin, a fibrate, and fish oils.
- Combination therapy with statins and niacin, fish oils, or fibrates can be considered for the secondary prevention of CVD in patients with elevated LDL-C and very high TGs. [C]
- Combination therapy with niacin and fibrates can be considered for the secondary prevention of CVD in patients with elevated LDL-C and very high TGs in patients unable to tolerate statins. [C]
Very High Triglycerides and/or Low HDL-C Without Elevated LDL-C
- For secondary prevention of CVD in patients with either low HDL-C or very high triglycerides and no elevation of LDL-C levels, combination therapy with statin plus niacin, fibrate, or fish oil may be considered. [C]
- Combination therapy with niacin and fibrates and/or fish oils can be considered in patients unable to tolerate statins. [C]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Combination lipid-lowering therapy should include a statin unless the patient is unable to tolerate statins |
Colhoun et al., 2004
Heart Protection Study Collaborative Group, 2004
|
I |
Substantial |
A |
2 |
In combination therapy with a statin, the lowest possible dose of statin should be used to achieve lipid goals and minimize complications |
Work Group Consensus |
III |
Poor |
C |
3 |
Combination therapy should be reserved for patients on secondary prevention |
Work Group Consensus |
III |
Poor |
I |
4 |
Addition of niacin to the statin can be considered in patients on secondary prevention not meeting their LDL-C goals on maximally tolerated doses of statins |
Zhou et al., 2004 |
I |
Good |
B |
5 |
Addition of a resin to the statin can be considered in patients not meeting their LDL-C goals on maximally tolerated doses of statins |
Brown et al., 1990 |
I |
Good |
B |
6 |
Addition of ezetimibe to the statin can be considered for lowering LDL-C levels in patients not meeting their LDL-C goals on maximally tolerated doses of statins and unable to tolerate niacin or a resin |
Gagne et al., 2002 |
I |
Good |
I |
7 |
Combination of resin and niacin can be considered in patients unable to tolerate statins and not achieving their LDL-C goals with niacin or resins alone |
Blankenhorn et al., 1987
Brown et al, 1990
|
II |
Good |
B |
8 |
Combination of statins and niacin, fish oils, or fibrates can be considered in patients with elevated LDL-C and very high TGs |
Working Group Consensus based upon clinical reasoning |
III |
Poor |
C |
9 |
Combination of niacin and fibrates can be considered in patients with elevated LDL-C and very high TGs who are unable to tolerate statins |
Working Group Consensus based upon clinical reasoning |
III |
Poor |
C |
10 |
Combination of statin and niacin, fibrate, or fish oil may be considered in patients who have achieved their LDL-C goal or are without elevated LDL-C, and have either low HDL-C or very high TGs |
Working Group Consensus based upon clinical reasoning |
III |
Poor |
C |
11 |
Combination of niacin and fibrates and/or fish oils can be considered in patients with elevated LDL-C very high TGs who are unable to tolerate statins |
Working Group Consensus based upon clinical reasoning |
III |
Poor |
C |
QE = Quality of Evidence; OQ = Overall Quality; SR = Strength of Recommendation (see Appendix A in the original guideline document)
- Repeat Dyslipidemia Evaluation in 1 to 2 Years (Patients NOT on Therapy)
Objective
Provide appropriate clinical follow-up for patients not on therapy.
Recommendation
- 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 CV 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.
Follow-up of Therapy Algorithm
- Address Adherence to Therapy
Objective
Identify causes of inadequate response to therapy following dose or stepwise titration.
Recommendations
- Adherence to therapy should be assessed at every visit, through history, pill count, and/or administrative records especially if therapeutic goals have not been reached [I]
- Adherence to lipid-lowering medication regimens may be improved by a multi-pronged approach [I] including:
- Evaluation of medication side effects
- Simplifying medication regimens to incorporate patient preference
- Addressing barriers for obtaining the medications (administrative, economic, etc.)
- Coordination with other healthcare team members to improve monitoring of adherence with prescriptions of pharmacological and lifestyle modification
- Patient and family education about their disease/treatment regimens
- Evaluation for depression
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Assess medication adherence at each visit through history, pill count, or medical record review |
Working Group Consensus |
III |
Poor |
I |
2 |
Consider a multi-pronged approach to improve adherence to medication regimens |
Working Group Consensus |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Does The Patient Have Elevated TG Level, or Low HDL-C Level, or Metabolic Syndrome?
The goal of dyslipidemia management is ultimately to decrease CV risk, and the evidence is best at reducing such risk through LDL-C lowering therapies. LDL-C remains the treatment priority, and should be addressed regardless of the TG level. Once the LDL-C goal has been reached, treatment attention may shift to obtain optimal lipoprotein profiles.
- Evaluation and Treatment of High Triglycerides
Objective
Evaluate and treat TG levels above 200 mg/dL.
Treatment for Hypertriglyceridemia |
TG >200 to 499 mg/dL |
TG >500 mg/dL |
TG >1000 mg/dL |
- Lifestyle management
- Weight loss
- Alcohol cessation
- Secondary causes
|
- Very low fat diet
- Low concentrated carbohydrate diet
- Alcohol cessation
- Secondary causes
- Consider drugs, if no response to above
- Consider referral
|
- Strict MNT (avoidance of alcohol, fat, and restrict calories)
- Secondary causes
- Drug therapy, if no response to above
- Consider referral
|
Recommendations
- Patients with elevated TG (>200 mg/dL) should have a repeat fasting lipid profile and, if persistent, receive intensive MNT, an appropriate exercise program, and be screened for underlying causes. [B]
- Drug therapy may be considered in patients with very high TG levels (> 500 mg/dL) that do not respond to lifestyle interventions and the treatment of underlying causes of elevated TG, for the purpose of preventing pancreatitis. [I]
- Effective drugs for lowering hypertriglyceridemia include fibrates, niacin, and fish oil. [B]
Table. Drug Treatment for Hypertriglyceridemia
TG 500 to 1000 mg/dL |
|
Drug |
Efficacy (Expected % Reduction in TG) |
Initial |
Fibrates |
-20 to -50 |
Alternate |
Niacin |
-20 to -35
|
n-3 PUFA Supplements, Omega-3 Fatty Acids/Fish Oils |
-20 to -30 |
- Fibrates are contraindicated in severe renal disease.
- Niacin is contraindicated in hepatic disease and relatively contraindicated in DM, gout, and history of complicated/active peptic ulcer disease (PUD).
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Elevated TG should receive intensive MNT, exercise, and screening for underlying causes |
NCEP ATP-III, 2002
Stone & Blum, 2002
|
II-3 |
Fair |
B |
2 |
Consider drug therapy to prevent pancreatitis |
Cleeman, 1998
NCEP ATP-III, 2002
Stone & Blum, 2002
|
III |
Poor |
I |
3 |
Use of fibrates, niacin, and fish oil to lower hypertriglyceridemia |
Farmer et al., 2001
Harris, 1997
|
I |
Fair |
B |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Evaluation and Treatment of Low HDL-C
Objective
Reduce risk of CVD through raising the level of HDL-C.
Recommendations
- Patients with CVD who have low HDL-C (<40 mg/dL), TG >200 mg/dL, and normal levels of LDL-C may benefit from gemfibrozil therapy. [A]
- Lifestyle modifications, including weight loss, exercise, and smoking cessation should be given high priority in the therapeutic plan for patients with low HDL-C. [B]
- CVD patients with low HDL-C (<40 mg/dL) may be considered for treatment with niacin. [B]
Table. Drug Treatment for Isolated Low HDL-C
LDL-C <130 and Low HDL-C |
Drug |
Efficacy (Expected % Reduction in TG) |
Gemfibrozil |
LDL-C
+10 to –35
|
HDL-C
+2 to 34
|
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
CVD patients with HDL-C <40 mg/dL, triglycerides >200 mg/dL, benefit from gemfibrozil therapy |
Robins, Collin, & Rubins, 1999 |
I |
Good |
A |
2 |
Lifestyle modifications, including weight reduction, smoking cessation, and exercise improve HDL-C level.
Aerobic exercise
Weight loss
|
Dattilo & Kris-Etherton, 1992
Haskell et al., 1988
Kokkinos et al., 1995
Superko & Haskell, 1987
Wood et al., 1991
|
II |
Fair |
B |
3 |
CVD patients with low HDL-C, may benefit from niacin |
King et al., 1994
Lavie et al., 1992
Miller et al., 1993; 1995
Vega & Grundy, 1989
|
I |
Fair |
B |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Evaluation and Treatment of Metabolic Syndrome
Objective
Identify therapeutic treatment options for individuals with metabolic syndrome.
Recommendations
- TLC should be initiated for patients diagnosed with metabolic syndrome. [B]
- Lifestyle modification for weight reduction through diet and increased physical activity is indicated for patients diagnosed with metabolic syndrome. [B]
- Drug therapy to alter insulin resistance or low HDL-C or elevated TG has not been demonstrated to improve CVD outcomes in patients with metabolic syndrome and as such, clinicians will have to individualize therapy. [I]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
TLC should be initiated for patient in which metabolic syndrome is indicated |
NCEP ATP-III, 2002 |
III |
Fair |
B |
2 |
Lifestyle modification for weight reduction through diet and increased physical activity is indicated for obese patients (BMI is >30) |
NCEP ATP-III, 2002 |
III |
Fair |
B |
3 |
Individualize drug therapy for modification of insulin resistance or dyslipidemia in the presence of metabolic syndrome using clinical judgment |
Working Group Consensus |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Reschedule Lipids Evaluation at Appropriate Time and Follow Up to Maintain Goals
Objective
Measure the efficacy of prescribed therapy for hyperlipidemia after allowing sufficient time to reach a new steady state.
Recommendations
- Lipid profiles should be reevaluated after at least 6 to 12 weeks of drug therapy or change in dose or after at least three to six months of dietary therapy to document efficacy, identify adverse effects, and to titrate medication dose. [I]
- Follow-up visits should [I] include:
- Patient history
- Physical exam
- Laboratory tests
- Documentation of adverse events
- Once the goal is achieved, therapy for dyslipidemia should be continued to maintain the goal. Treatment of dyslipidemia is a lifelong process; however, adjustments may be necessary if the patient develops medical conditions that affect the severity of comorbidity or life expectancy.
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Reevaluate serum lipids after at least 6 to 12 weeks of therapy or after at least three to six months of TLC |
Working Group Consensus |
III |
Poor |
I |
2 |
Follow-up visits should include: patient history, physical exam, lab tests, and adverse event documentation |
Working Group Consensus |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
- Follow Up, Repeat Lipid Evaluation At Least Annually
Objective
Ensure that patients initially treated for dyslipidemia receive periodic reassessment of the efficacy of treatment.
Recommendations
- Lipid evaluations should be repeated at least annually. [I]
|
Recommendation |
Sources of Evidence |
QE |
Overall Quality |
R |
1 |
Perform periodic follow up |
NCEP ATP-III, 2002 |
III |
Poor |
I |
QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A in the original guideline document)
Definitions:
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.
|
Net Benefit of the Intervention |
Quality of Evidence |
Substantial |
Moderate |
Small |
Zero or Negative |
Good |
A |
B |
C |
D |
Fair |
B |
B |
C |
D |
Poor |
I |
I |
I |
I |
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
Abbreviations and Acronyms List
ACS – acute coronary syndrome
AIDS – acquired immune deficiency syndrome
ALT – alanine aminotransferase
AST– aspartate aminotransferase
AMI– acute myocardial infarction
BMI – body mass index
CAD – coronary artery disease
CHD – coronary heart disease
CK – creatine kinase
CV – cardiovascular
CVA – cerebrovascular accident
CVD – cardiovascular disease
DM – diabetes mellitus
HbAlc – glycosylated hemoglobin A1C
HDL-C – high density lipoprotein cholesterol
HIV – human immunodeficiency virus
HsCRP – high sensitive C-reactive protein
HTN – hypertension
LDL-C – low density lipoprotein cholesterol
LFT – liver function tests
MI – myocardial infarction
MNT – Medical Nutrition Therapy
PUD – peptic ulcer disease
SCr – serum creatine
TC – total cholesterol
TG – triglycerides
TLC – therapeutic lifestyle change
TSH – thyroid-stimulating hormone