Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm
Publication Date: October 1, 2020
Last Updated: March 14, 2022
Recommendations
SCREENING FOR DYSLIPIDEMIA
R1. Identify risk factors that enable personalized and optimal therapy for dyslipidemia. (IA)
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R2. Based on epidemiologic studies, individuals with type 2 diabetes (T2DM) should be considered as high, very high, or extreme risk for ASCVD. (IIIB)
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R3. Based on epidemiologic and prospective cohort studies, individuals with type 1 diabetes (T1DM) and duration more than 15 years or with 2 or more major cardiovascular (CV) risk factors (e.g., albu minuria, chronic kidney disease [CKD] stage 3/4, initiation of intensive control >5 years after diagnosis), poorly controlled hemoglobin A1C (A1C) or insulin resistance with metabolic syndrome should be considered to have risk-equivalence to individuals with T2DM. (IIB)
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R4. The 10-year risk of a coronary event (high, intermediate, or low) should be determined by detailed assessment using one or more of the following tools. (IVC)
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R5. Special attention should be given to assessing women for ASCVD risk by determining the 10-year risk (high, intermediate, or low) of a coronary event using the Reynolds Risk Score (http://www.reynoldsriskscore.org) or the Framingham Risk Assessment Tool (http://www.framinghamheartstudy.org/risk-functions/coronary-heart-disease/hard-10- year-risk.php). (IV, C)
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R6. Dyslipidemia in childhood and adolescence should be diagnosed and managed as early as possible to reduce the levels of LDL-C that may eventually increase risk of CV events in adulthood. (IA)
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R7. When the HDL-C concentration is >60 mg/dL, 1 risk factor should be subtracted from an individual’s overall risk profile. (IIB)
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R8. A classification of elevated TG should be incorporated into risk assessments to aid in treatment decisions. (IIB)
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R9. Individuals should be screened for familial hypercholesterolemia (FH) when there is a family history of:
- Premature ASCVD (definite MI or sudden death before age 55 years in father or other male first- degree relative, or before age 65 years mother or other female first-degree relative) or
- Elevated cholesterol levels (total, non-HDL and/ or LDL) consistent with FH.
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R10. Annually screen all adult individuals with T1DM or T2DM for dyslipidemia. (IIB)
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R11. Evaluate all adults 20 years of age or older for dyslipidemia every 5 years as part of a global risk assessment. (IVC)
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R12. In the absence of ASCVD risk factors, screen middle-aged individuals for dyslipidemia at least once every 1 to 2 years. More frequent lipid testing is recommended when multiple global ASCVD risk factors are present. (IA)
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R13. The frequency of lipid testing should be based on individual clinical circumstances and the clinician’s best judgment. (IVC)
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R14. Annually screen older adults with 0 to 1 ASCVD risk factor for dyslipidemia. (IA)
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R15. Older adults should undergo lipid assessment if they have multiple ASCVD global risk factors (i.e., other than age). (IVC)
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R16. Screening for this group is based on age and risk, but not sex; therefore, older women should be screened in the same way as older men. (IA)
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R17. In children at risk for FH (e.g., family history of premature cardiovascular disease or elevated cholesterol), screening should be at 3 years of age, again between ages 9 and 11, and again at age 18. (IIIB)
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R18. Screen adolescents older than 16 years every 5 years or more frequently if they have ASCVD risk factors, have overweight or obesity, have other ele-ments of the insulin resistance syndrome, or have a family history of premature ASCVD. (IIIB)
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SCREENING FOR CARDIOVASCULAR RISK
R19. Use a fasting lipid profile to ensure the most precise lipid assessment; this should include total cholesterol, LDL-C, TG, and non-HDL-C. (IVC)
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R20. Lipids, including TG, can be measured in the non-fasting state if fasting determinations are impractical. (D)
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R21. LDL-C may be estimated using the Friedewald equation: LDL-C = (total cholesterol minus HDL-C) - TG/5; however, this method is valid only for values obtained during the fasting state and becomes increasingly inaccurate and invalid when TG levels are greater than 200 mg/dL and 400 mg/dL, respectively. (IIIC)
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R22. LDL-C should be directly measured in certain high-risk individuals such as those with fasting TG levels greater than 250 mg/dL or those with diabetes or known vascular disease. (IIIC)
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R23. Measurement of HDL-C should be included in screening tests for dyslipidemia. (IIB)
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R24. The non-HDL-C (total cholesterol minus HDL-C) should be calculated to assist risk stratification in individuals with moderately elevated TG (200 to 500 mg/dL), diabetes, and/or established ASCVD. (IIB)
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R25. If insulin resistance is suspected, the non-HDL-C should be evaluated to gain useful information regarding the individual’s total atherogenic lipoprotein burden. (D)
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R26. TG levels should be part of routine lipid screening: moderate elevations (≥150 mg/dL) may identify individuals at risk for the insulin resistance syndrome and levels ≥200 mg/dL may identify individuals at substantially increased ASCVD risk. (IIB)
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R27. Apo B and/or an apo B/apo A1 ratio calculation and evaluation may be useful in at-risk individuals (TG ≥150, HDL-C <40, prior ASCVD event, T2DM, and/or the insulin resistance syndrome [even at target LDL-C levels]) to assess residual risk and guide decision-making. (IA)
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R28. Apo B measurements (reflecting the particle concentration of LDL and all other atherogenic lipoproteins) may be useful to assess the success of LDL-C- lowering therapy. (IA)
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R29. Rule out secondary causes of dyslipidemia. (IIB)
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R30. Use hsCRP to stratify ASCVD risk in individuals with a standard risk assessment that is borderline, or in those with an intermediate or higher risk with an LDL-C concentration <130 mg/dL. (IIB)
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R31. Measure lipoprotein-associated phospholipase A2 (Lp-PLA2), which in some studies has demonstrated more specificity than hsCRP, when it is necessary to further stratify an individual’s ASCVD risk, especially in the presence of hsCRP elevations. (IA)
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R32. The routine measurement of homocysteine, uric acid, plasminogen activator inhibitor-1, or other inflammatory markers is not recommended because the benefit of doing so is not sufficiently proven. (D)
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R33. Coronary artery calcification (CAC) measurement has been shown to be of high predictive value and is useful in refining risk stratification to determine the need for more aggressive treatment strategies. (IIB)
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R34. Carotid intima media thickness (CIMT) may be considered to refine risk stratification to determine the need for more aggressive ASCVD preventive strategies, (IIB)
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TREATING DYSLIPIDEMIA AND ASCVD RISK
R35. Treatment goals for dyslipidemia should be personalized according to levels of risk. (IA)
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R36. For individuals at low risk (i.e., with no risk factors), an LDL-C goal <130 mg/dL is recommended. (IA)
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R37. For individuals at moderate risk (i.e., with 2 or fewer risk factors and a calculated 10-year risk of less than 10%), an LDL-C goal <100 mg/dL is recommended. (IA)
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R38. For individuals at high risk (i.e., with an ASCVD equivalent including diabetes or stage 3 or 4 CKD with no other risk factors, or individuals with 2 or more risk factors and a 10-year risk of 10%- 20%), an LDL-C goal <100 mg/dL is recommended. (IA)
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R39. For individuals at very high risk (i.e., with established or recent hospitalization for acute coronary syndrome (ACS); coronary, carotid or peripheral vascular disease; diabetes or stage 3 or 4 CKD with 1 or more risk factors; a calculated 10-year risk greater than 20%; or heterozygous familial hypercholesterolemia [HeFH]), an LDL-C goal <70 mg/dL is recommended. (IA)
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R40. For individuals at extreme risk (i.e., with progressive ASCVD, including unstable angina that persists after achieving an LDL-C <70 mg/dL, or established clinical ASCVD in individuals with diabetes, stage 3 or 4 CKD, and/or HeFH, or in individuals with a history of premature ASCVD (<55 years of age for males or <65 years of age for females), an LDL-C goal <55 mg/dL is recommended. (IA)
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R41. An LDL-C goal <100 mg/dL is considered “acceptable” for children and adolescents, with 100 to 129 mg/dL considered “borderline” and 130 mg/dL or greater considered “high” (based on recommendations from the American Academy of Pediatrics) (D)
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R42. HDL-C should be >40 mg/dL, but also as high as possible, primarily through the use of lifestyle interventions (e.g., weight loss, physical activity, and tobacco cessation), and if risk factors are present (e.g., borderline elevated LDL-C levels, a family history of premature ASCVD, or a personal history of ASCVD), also through the use of pharmacotherapy primarily focused on reducing LDL-C. (IA)
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43. For most individuals, a non-HDL-C goal (total cholesterol - HDL-C) 30 mg/dL higher than the individual’s specific LDL-C goal is recommended. (D)
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R44. For individuals at extreme risk, a non-HDL- C goal 25 mg/dL higher than the individual-specific LDL-C goal is recommended. (IA)
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R45. For individuals at increased risk of ASCVD, including those with diabetes, an optimal apo B goal is <90 mg/dL, while for individuals with established ASCVD or diabetes plus 1 or more additional risk factor(s), an optimal apo B goal is <80 mg/dL, and for individuals at extreme risk, an optimal apo B goal is <70 mg/dL. (IA)
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R46. TG goals <150 mg/dL are recommended. (IA)
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R47. A comprehensive strategy to control lipid levels and address associated metabolic abnormalities and modifiable risk factors is recommended primarily using lifestyle changes. (IA)
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- and patient education with pharmacotherapy as needed to achieve evidence-based targets.
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R48. A reasonable and feasible approach to fitness therapy (i.e., exercise programs that include at least 30 minutes of moderate-intensity physical activity [consuming 4-7 kcal/min] 4 to 6 times weekly, with an expenditure of at least 200 kcal/day) is recommended; suggested activities include brisk walking, riding a stationary bike, water aerobics, cleaning/ scrubbing, mowing the lawn, and sporting activities. (IA)
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R49. Daily physical activity goals can be met in a single session or in multiple sessions throughout the course of a day (10 minutes minimum per session); for some individuals, breaking activity up throughout the day may help improve adherence with physical activity programs. (IA)
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R50. In addition to aerobic activity, muscle-strengthening activity is recommended at least 2 days a week. (IA)
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R51. For adults, a reduced-calorie diet consisting of fruits and vegetables (combined >5 servings/day), grains (primarily whole grains), fish, and lean meats is recommended. (IA)
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R52. For adults, the intake of saturated fats, transfats, and cholesterol should be limited, while LDL-C-lowering macronutrient intake should include plant stanols/sterols (~2 g/day) and soluble fiber (10-25 g/ day). (IA)
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R53. Primary preventive nutrition consisting of healthy lifestyle habits is recommended in all healthy children. (IA)
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R54. Tobacco cessation should be strongly encouraged and facilitated. (IIA)
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R55. In individuals at risk for ASCVD, aggressive lipid-modifying therapy is recommended to achieve appropriate LDL-C goals. (IA)
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R56. Statin therapy is recommended as the primary pharmacologic agent to achieve target LDL-C goals on the basis of morbidity and mortality outcome trials. (IA)
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R57. For clinical decision-making, mild elevations in blood glucose levels and/or an increased risk of new- onset T2DM associated with intensive statin therapy do not outweigh the benefits of statin therapy for ASCVD risk reduction. (IA)
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R59. Very high-risk individuals with established coronary, carotid, and peripheral vascular disease, or diabetes who also have at least 1 additional risk factor should be treated with statins to target a reduced LDL-C treatment goal of <70 mg/dL. (IA)
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R60. Extreme-risk individuals should be treated with statins to target an even lower LDL-C treatment goal of <55 mg/dL. (IA)
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R61. Fibrates should be used to treat severe hypertriglyceridemia (TG >500 mg/dL). (IA)
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R62. Fibrates may improve ASCVD outcomes in primary and secondary prevention when TG concentrations are >200 mg/dL and HDL-C concentrations are <40 mg/dL. (IA)
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R63. Prescription omega-3 oil, 2 to 4 g daily, should be used to treat severe hypertriglyceridemia (TG >500 mg/dL). Dietary supplements are not FDA-approved for treatment of hypertriglyceridemia and generally are not recommended for this purpose. (IA)
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R64. Niacin therapy is recommended principally as an adjunct for reducing TG. (IA)
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R65. Niacin therapy should not be used in individuals aggressively treated with statin due to absence of additional benefits with well-controlled LDL-C. (IA)
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R66. Bile acid sequestrants may be considered for reducing LDL-C and apo B and modestly increasing HDL-C, but they may increase TG. (IA)
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R67. Ezetimibe may be considered as monotherapy in reducing LDL-C and apo B, especially in statin-intolerant individuals. (IIB)
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R68. Ezetimibe can be used in combination with statins to further reduce both LDL-C and ASCVD risk. (IA)
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R69. PCSK9 inhibitors should be considered for use in combination with statin therapy for LDL-C lowering in individuals with FH. (IA)
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R70. PCSK9 inhibitors should be considered in individuals with clinical cardiovascular disease who are unable to reach LDL-C/non-HDL-C goals with maximally tolerated statin therapy. They should not be used as monotherapy except in statin-intolerant individuals. (IA)
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R71. Combination therapy of lipid-lowering agents should be considered when the LDL-C/non-HDL-C level is markedly increased and monotherapy (usually with a statin) does not achieve the therapeutic goal. (IA)
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R72. Women should be evaluated for their ASCVD risk and be treated with pharmacotherapy if lifestyle intervention is insufficient. (IVC)
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R73. Hormone replacement therapy for the treatment of dyslipidemia in postmenopausal women is not recommended. (IA)
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R74. Pharmacotherapy is recommended for children and adolescents older than 10 years who do not respond sufficiently to lifestyle modification, particularly for those satisfying the following criteria. (IVD)
- LDL-C >190 mg/dL
- LDL-C >160 mg/dL and the presence of 2 or more cardiovascular risk factors, even after vigorous intervention
- Family history of premature ASCVD (before 55 years of age), or
- Having overweight, obesity, or other elements of the insulin resistance syndrome.
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R75. Re-assess individuals’ lipid status 6 weeks after therapy initiation and again at 6-week intervals until the treatment goal is achieved. (IVD)
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R76. While on stable lipid therapy, individuals should be tested at 6- to 12-month intervals. (IVD)
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R77. While on stable lipid therapy, the specific interval of testing should depend on individual adherence to therapy and lipid profile consistency. If adherence is a concern or the lipid profile is unstable, the individual will probably benefit from more frequent assessment. (IVC)
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R78. More frequent lipid status evaluation is recommended in situations such as deterioration of diabetes control, use of a new drug known to affect lipid levels, progression of atherothrombotic disease, considerable weight gain, unexpected adverse change in any lipid parameter, development of a new ASCVD risk factor, or convincing new clinical trial evidence or guidelines that suggest stricter lipid goals. (IVC)
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R79. Liver transaminase levels should be measured before and 3 months after niacin or fibric acid treatment initiation because most liver abnormalities occur within 3 months of treatment initiation. Liver transaminase levels should be measured periodically thereafter (e.g., semiannually or annually). (IVC)
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R80. Creatine kinase levels should be assessed and the statin discontinued, at least temporarily, when an individual reports clinically significant myalgias or muscle weakness on statin therapy. (IVC)
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COST-EFFECTIVENESS OF TREATMENT
R81. Nonpharmacologic interventions such as dietary management (IA)
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- and smoking cessation are the most cost-effective options available for ASCVD prevention.
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R82. When nonpharmacologic interventions fail, pharmacologic intervention is a recommended cost-effective option for primary and secondary intervention among individuals at moderate to high risk. (IIB)
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R83. Among otherwise healthy individuals at lower risk, the cost-effectiveness of primary pharmacologic intervention varies on the basis of age and sex (with this approach being least cost-effective among women at low risk). (IIIC)
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R84. Statins have proven cost-effective in both secondary and primary prevention of ASCVD events in individuals at moderate to high risk or in individuals at low risk whose LDL-C levels are very high (>190 mg/ dL). (IIB)
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R85. Treatment with fibrates has been found to be cost-effective as both monotherapy and combination therapy for lowering TG and raising HDL-C (IVD)
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- but not in reducing cardiovascular events, except in individuals with TG concentrations greater than 200 mg/dL and HDL-C concentrations less than 40 mg/dL.
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R86. Ezetimibe, co-administered with statin therapy in individuals unable to meet target LDL-C levels, has not been evaluated for cost-effectiveness in the U.S. Based on studies from Canada and the United Kingdom, ezetimibe may be a cost-effective strategy to achieve LDL-C goals, especially with price decreases for generic ezetimibe. (IA)
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R87. Bile acid sequestrants are generally not cost- effective alternatives to statin therapy despite generic availability; this is due to their low LDL-C lowering efficacy compared to statins. (IIB)
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Recommendation Grading
Overview
Title
Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm
Authoring Organization
American Association of Clinical Endocrinologists
Publication Month/Year
October 1, 2020
Last Updated Month/Year
February 6, 2024
Supplemental Implementation Tools
Document Type
Consensus
External Publication Status
Published
Country of Publication
US
Inclusion Criteria
Female, Male, Adult, Older adult
Health Care Settings
Ambulatory
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Prevention, Management
Diseases/Conditions (MeSH)
D050171 - Dyslipidemias, D002318 - Cardiovascular Diseases
Keywords
atherosclerotic cardiovascular disease, cardiovascular disease, dyslipidemia, prevention