CHOLESTEROL GUIDELINES










High-intensity statin therapy
(lowers cholesterol by ≥50%)		 Moderate-intensity statin therapy
(lowers cholesterol by 30 - 50%)		 Low-intensity statin therapy
(lowers cholesterol by < 30%)
  • Atorvastatin (Lipitor®) 40 - 80 mg/day
  • Rosuvastatin (Crestor®) 20 - 40 mg/day
  • Atorvastatin (Lipitor®) 10 - 20 mg/day
  • Rosuvastatin (Crestor®) 5 - 10 mg/day
  • Simvastatin (Zocor®) 20 - 40 mg/day
  • Pravastatin (Pravachol®) 40 - 80 mg/day
  • Lovastatin (Mevacor®) 40 mg/day
  • Fluvastatin XL (Lescol XL®) 80 mg/day
  • Fluvastatin (Lescol®) 40 mg twice/day
  • Pitavastatin (Livalo®) 2 - 4 mg/day
  • Simvastatin (Zocor®) 10 mg/day
  • Pravastatin (Pravachol®) 10 - 20 mg/day
  • Lovastatin (Mevacor®) 20 mg/day
  • Fluvastatin (Lescol®) 20 - 40 mg/day
  • Pitavastatin (Livalo®) 1 mg/day


  • Reference [5]
AHA/ACC 2018 Screening Recommendations
Adults
  • In adults ≥ 20 years of age and not on lipid-lowering therapy, measurement of either a fasting or a nonfasting plasma lipid profile is effective in estimating ASCVD risk and documenting baseline LDL
  • In adults ≥ 20 years of age and in whom an initial nonfasting lipid profile reveals a triglycerides level ≥ 400 mg/dl, a repeat lipid profile in the fasting state should be performed for assessment of fasting triglyceride levels and baseline LDL
Children
  • In children and adolescents with a family history of either early CVD or significant hypercholesterolemia, it is reasonable to measure a fasting or nonfasting lipoprotein profile as early as age 2 years to detect familial hypercholesterolemia or rare forms of hypercholesterolemia
  • In children and adolescents with obesity or other metabolic risk factors, it is reasonable to measure a fasting lipid profile to detect lipid disorders as components of the metabolic syndrome
  • In children and adolescents without cardiovascular risk factors or family history of early CVD, it may be reasonable to measure a fasting lipid profile or nonfasting non HDL once between the ages of 9 and 11 years, and again between the ages of 17 and 21 years, to detect moderate to severe lipid abnormalities

  • Reference [2]
USPSTF Screening Recommendations
Women
  • Women not at increased risk - no recommendation to screen
  • Women at increased risk - screen every 5 years
Increased risk defined as presence of one of the following:
  • Diabetes
  • Personal history of atherosclerosis
  • Family history of cardiovascular disease in male relatives < 50 years or female relatives < 60 years
  • Tobacco use
  • Hypertension
  • Obesity (BMI ≥ 30)
Men
  • Men not at increased risk - screen at 35 years old
  • Men at increased risk - screen every 5 years starting at age 20
Increased risk defined as presence of one of the following:
  • Diabetes
  • Personal history of atherosclerosis
  • Family history of cardiovascular disease in male relatives < 50 years or female relatives < 60 years
  • Tobacco use
  • Hypertension
  • Obesity (BMI ≥ 30)


  • Reference [5]
AHA/ACC 2018 Primary Prevention Recommendations
Any patient with diabetes
Age 0 - 19 years
  • Lifestyle modification for most
  • If Familial Hypercholesterolemia is suspected, see below
Age 20 - 75 years old and LDL ≥ 190 mg/dl
  • High-intensity statin (or max tolerated)
Response
  • If LDL reduction is < 50% and/or LDL is ≥ 100 mg/dl, adding ezetimibe is reasonable
  • If LDL reduction is < 50% while taking statin + ezetimibe and triglycerides ≤ 300 mg/dl, the addition of a bile acid sequestrant may be considered
Age 20 - 39 years and LDL 70 - 189 mg/dl
  • Consider statin if family history of premature ASCVD and LDL ≥ 160 mg/dl
  • Premature ASCVD defined as ASCVD in males < 55 years and females < 65 years
Age 40 - 75 years and LDL 70 - 189 mg/dl
  • Step 1: Estimate 10-year ASCVD risk - AHA/ACC risk calculator
  • Step 2 - Categories:
    • Low risk: < 5%
    • Borderline risk: 5% - <7.5%
    • Intermediate risk: ≥7.5% - <20%
    • High risk: ≥ 20%
  • Step 3 - Treatment recommendations:
    • Low risk: lifestyle modification
    • Borderline risk: if risk enhancers are present, consider moderate-intensity statin
    • Intermediate risk: if risk enhancers are present, start moderate-intensity statin to reduce LDL by 30 - 49%
    • High risk: High-intensity statin
Age ≥ 75 years and LDL 70 - 189 mg/dl
  • Moderate-intensity statin may be reasonable
  • It may be reasonable to stop statin therapy when functional decline (physical or cognitive), multimorbidity, frailty, or reduced life-expectancy limits the potential benefits of statin therapy
  • In adults 76 to 80 years of age with an LDL level of 70 - 189 mg/dl, it may be reasonable to measure CAC to reclassify those with a CAC score of zero to avoid statin therapy

  • Reference [5]
Risk enhancers
  • Family history of premature ASCVD defined as ASCVD in a first-degree male relative < 55 years old or in a first-degree female relative < 65 years old
  • Primary hypercholesterolemia defined as LDL of 160 – 189 mg/dL or non–HDL of 190 – 219 mg/dL
  • Metabolic syndrome defined as having any 3 of the following:
    • Increased waist circumference
    • Triglycerides > 175 mg/dl
    • Elevated blood pressure
    • Elevated glucose
    • Low HDL (< 40 mg/dl in men; <50 mg/dl in women)
  • Chronic kidney disease (GFR 15 - 59 ml/min) not treated with dialysis or kidney transplantation
  • Chronic inflammatory conditions such as psoriasis, rheumatoid arthritis, or HIV/AIDS
  • History of premature menopause (before age 40 years) and/or history of pregnancy-associated conditions that increase later ASCVD risk such as preeclampsia
  • High-risk race/ethnicity (e.g. South Asian ancestry, Puerto Ricans, black females, Native American/Alaskan)
  • Any of the following lipid/biomarkers associated with ASCVD:
    • Persistently elevated, primary hypertriglyceridemia (≥ 175 mg/dl)
    • Elevated high-sensitivity C-reactive protein (≥ 2.0 mg/l)
    • Lipoprotein (a) ≥ 50 mg/dl or ≥ 125 nmol/l
    • Apolipoprotein B (apoB) ≥ 130 mg/dl
    • Ankle-brachial index (ABI) < 0.9

  • Reference [2]
USPSTF 2016 Primary Prevention Recommendations
Use a low- to moderate-intensity statin in patients who meet all of the following criteria:
  • Age 40 - 75 years
  • One or more cardiovascular disease risk factors is present (e.g. high cholesterol (defined as LDL ≥ 130 mg/dl), diabetes, hypertension, smoking)
  • Estimated 10-year risk of a cardiovascular event is ≥ 10% (ASCVD risk calculator) [Grade B]
A low- to moderate-intensity statin may be beneficial in some patients who meet all of the following criteria:
  • Age 40 - 75 years
  • One or more cardiovascular disease risk factors is present (e.g. high cholesterol (defined as LDL ≥ 130 mg/dl), diabetes, hypertension, smoking)
  • Estimated 10-year risk of a cardiovascular event is 7.5% - 10% (ASCVD risk calculator) [Grade C]
Age ≥ 76 years
  • There is insufficient evidence to make a recommendation

  • Reference [5]
AHA/ACC 2018 Secondary Prevention Recommendations
Risk categories
  • The AHA 2018 guidelines categorize patient with ASCVD into two groups:
    • ASCVD not at very high-risk
    • Very high-risk ASCVD
  • See ASCVD secondary risk categories below for definitions
Age ≤ 75 years and not at very-high risk
  • High-intensity statin or maximally-tolerated statin with goal of ≥ 50% LDL reduction
Response
  • If LDL is ≥ 70 mg/dl, adding ezetimibe is reasonable
Age > 75 years and not at very-high risk
  • Initiation of moderate- or high-intensity statin is reasonable
  • Continuation of high-intensity statin is reasonable
Any age and very high-risk ASCVD
  • High-intensity statin or maximally-tolerated statin
Response
  • If LDL is ≥ 70 mg/dl, adding ezetimibe is reasonable
  • If LDL is ≥ 70 mg/dl or non-HDL ≥ 100 mg/dl on statin + ezetimibe, adding PCSK9 inhibitor is reasonable

  • Reference [5]
ASCVD Secondary Risk Categories
  • Very high-risk definition: Patients are considered very high-risk if they have had ≥ two major ASCVD events or have had one major ASCVD event and have multiple high-risk conditions
Major ASCVD events
  • Acute coronary syndrome (ACS) within the past 12 months
  • History of myocardial infarction (other than recent ACS event listed above)
  • History of ischemic stroke
  • Symptomatic peripheral arterial disease (history of claudication with ABI < 0.85, or previous revascularization or amputation)
High-risk conditions
  • Age ≥ 65 years
  • Heterozygous familial hypercholesterolemia
  • History of prior coronary artery bypass surgery or percutaneous coronary intervention outside of the major ASCVD event(s)
  • Diabetes
  • Hypertension
  • Chronic kidney disease (GFR 15 - 59 ml.min)
  • Current smoking
  • Persistently elevated LDL (≥ 100 mg/dl) despite maximally tolerated statin therapy and ezetimibe
  • History of congestive heart failure

  • Reference [7]
ADA Lipid Treatment Recommendations for Adults with Diabetes
Age < 40 years
  • No ASCVD and no ASCVD risk factors: No statin recommended
  • No ASCVD with ASCVD risk factors: Moderate-intensity statin may be considered
  • ASCVD present: High-intensity statin recommended. If LDL ≥ 70 mg/dl despite maximally tolerated statin, consider adding ezetimibe or PCSK9 inhibitor
  • Lipid levels should be monitored annually or as needed [46]
  • See statin intensity chart
Age ≥ 40 years
  • No ASCVD and no ASCVD risk factors: Moderate-intensity statin
  • No ASCVD with ASCVD risk factors: At the least, moderate-intensity statin. High-intensity statin should be considered. If 10-year CVD risk is ≥ 20%, it may be reasonable to add ezetimibe to maximally-tolerated statins in order to reduce LDL by ≥ 50%.
  • ASCVD present: High-intensity statin recommended. If LDL ≥ 70 mg/dl despite maximally tolerated statin, consider adding ezetimibe or PCSK9 inhibitor
  • Lipid levels should be monitored annually or as needed [46]
  • See statin intensity chart

  • Reference [7]
ADA ASCVD Risk Factors
  • LDL ≥ 100 mg/dl
  • Hypertension
  • Chronic kidney disease (GFR < 60 ml/min)
  • Albuminuria ≥30 mcg of albumin/mg creatinine
  • Smoking
  • History of premature ASCVD in a first-degree relative (ASCVD in males < 55 years and females < 65 years) [46]

  • Reference [7]
ADA Lipid Treatment Recommendations for Youth with Type 1 DM
Screening
  • Initial lipid testing should be performed when initial glycemic control has been achieved and age is ≥ 2 years
  • If initial LDL cholesterol is ≤ 100 mg/dL, subsequent testing should be performed at 9 - 11 years of age
  • If LDL cholesterol values are within the accepted risk level ( ≤ 100 mg/dL), a lipid profile repeated every 3 years is reasonable
Treatment
  • If lipids are abnormal, initial therapy should consist of optimizing glucose control and medical nutrition therapy to limit the amount of calories from fat to 25 – 30%, saturated fat to < 7%, cholesterol < 200 mg/day, avoidance of trans fats, and aim for approximately 10% calories from monounsaturated fats
  • After the age of 10 years, addition of a statin may be considered in patients who, despite medical nutrition therapy and lifestyle changes, continue to have LDL cholesterol > 160 mg/dL or LDL cholesterol > 130 mg/dL and one or more cardiovascular disease risk factors, following reproductive counseling because of the potential teratogenic effects of statins. [7]
  • The goal of therapy is LDL < 100 mg/dl

  • Reference [7]
ADA Lipid Treatment Recommendations for Youth with Type 2 DM
Screening
  • Lipid testing should be performed when initial glycemic control has been achieved and annually thereafter
Treatment
  • Optimal goals are LDL cholesterol < 100mg/dL, HDL cholesterol > 35 mg/dL, and triglycerides < 150 mg/dL
  • If LDL cholesterol is > 130 mg/dL, blood glucose control should be maximized and dietary counseling should be provided using the American Heart Association Step 2 diet
  • If LDL cholesterol remains above goal after 6 months of dietary intervention, initiate therapy with statin, with goal of LDL < 100 mg/dL [7]

  • Reference [7]
ADA Recommendations for HDL and Triglyceride Levels in Adults
  • Triglycerides ≥ 150 mg/dl and/or HDL cholesterol < 40 mg/dL for men, < 50 mg/dL for women - intensify lifestyle therapy and optimize glycemic control
  • Fasting triglycerides ≥ 500 mg/dl - evaluate for secondary causes of hypertriglyceridemia and consider medical therapy to reduce risk of pancreatitis
  • In patients with ASCVD or other cardiac risk factors on a statin with controlled LDL, but elevated triglycerides (135 - 499 mg/dl), the addition of icosapent ethyl should be considered to reduce cardiovascular risk.

  • Reference [7]
ADA Recommendations for Triglyceride Levels in Youth with Type 2 DM
  • If triglycerides are > 400 mg/dL fasting or > 1,000 mg/dL nonfasting, optimize glycemia and begin fibrate, with a goal of < 400 mg/dL fasting (to reduce risk for pancreatitis)

  • Reference [5]
AHA/ACC 2018 Primary Prevention in Diabetes Recommendations
Age 20 - 39 years
Age 40 - 75 years
  • At the least, a moderate-intensity statin is recommended in all patients regardless of risk category
  • If multiple ASCVD risk factors are present, a high-intensity statin with a goal of ≥ 50% LDL reduction is reasonable
  • For diabetics with a 10-year ASCVD risk ≥ 20% (AHA/ACC risk calculator), it is reasonable to add ezetimibe to maximally tolerated statin to reduce LDL by ≥ 50%
Age > 75 years
  • For patients already on a statin, it is reasonable to continue a statin
  • For patients not taking a statin, it may be reasonable to initiate a statin

  • Reference [5]
Diabetes-specific Risk Enhancers
  • Long duration (≥ 10 years for type two diabetes mellitus or ≥ 20 years for type one diabetes mellitus)
  • Albuminuria ≥ 30 mcg of albumin/mg creatinine
  • GFR < 60 ml/min
  • Retinopathy
  • Neuropathy
  • ABI < 0.9



  • Reference [5]
AHA/ACC 2018 Familial Hypercholesterolemia (FH) Recommendations
Age 0 - 19 years
  • Diagnosis
    • In children and adolescents with a family history of either early CVD or significant hypercholesterolemia, it is reasonable to measure a fasting or nonfasting lipoprotein profile as early as age 2 years to detect familial hypercholesterolemia or rare forms of hypercholesterolemia
    • In children and adolescents found to have moderate or severe hypercholesterolemia, it is reasonable to carry out reverse-cascade screening of family members, which includes cholesterol testing for first-, second-, and when possible, third-degree biological relatives, for detection of familial forms of hypercholesterolemia
  • Treatment
    • In children and adolescents 10 years of age or older with an LDL level persistently ≥ 190 mg/dl or ≥ 160 mg/dl with a clinical presentation consistent with FH and who do not respond adequately with 3 to 6 months of lifestyle therapy, it is reasonable to initiate statin therapy
    • Atorvastatin and rosuvastatin are FDA-approved in children with FH
Age 20 - 29 years with FH
  • High-intensity statin or maximally-tolerated statin
Response
  • If LDL reduction is < 50% and/or LDL is ≥ 100 mg/dl, adding ezetimibe is reasonable
  • If LDL reduction is < 50% while taking statin + ezetimibe and triglycerides ≤ 300 mg/dl, the addition of a bile acid sequestrant may be considered
Age 30 - 75 years with FH
  • High-intensity statin or maximally-tolerated statin
Response
  • If LDL ≥ 100 mg/dl, ezetimibe therapy is reasonable
  • If LDL ≥ 100 mg/dl on statin + ezetimibe, addition of PCSK9 inhibitor may be considered

  • Reference [5]
AHA/ACC 2018 Hypertriglyceridemia Recommendations
Triglyceride ranges
  • Normal: < 150 mg/dl
  • Mild hypertriglyceridemia: 150 - 174 mg/dl
  • Moderate hypertriglyceridemia: 175 - 499 mg/dl
  • Severe hypertriglyceridemia: ≥ 500 mg/dl
NOTE: Lipid profiles can be drawn fasting or nonfasting. If a nonfasting lipid profile reveals a triglyceride level ≥ 400 mg/dl, it should be repeated fasting.
Age 20 - 39 with moderate hypertriglyceridemia
  • Lifestyle modification (very low-fat diet, avoidance of refined carbohydrates and alcohol, consumption of omega-3 fatty acids)
  • Risk factor treatment (e.g. diabetes, obesity, medications)
  • See triglycerides for more
Age 20 - 39 with severe hypertriglyceridemia
  • Lifestyle modification (very low-fat diet, avoidance of refined carbohydrates and alcohol, consumption of omega-3 fatty acids)
  • Risk factor treatment (e.g. diabetes, obesity, medications). See triglycerides for more.
  • Consider fibrate therapy. Triglyceride levels ≥ 1000 mg/dl increase the risk of pancreatitis.
Age 40 - 75 with moderate hypertriglyceridemia
  • Step 1: Estimate 10-year ASCVD risk (AHA/ACC risk calculator)
  • Step 2:
    • All patients
      • Lifestyle modification (very low-fat diet, avoidance of refined carbohydrates and alcohol, consumption of omega-3 fatty acids)
      • Risk factor treatment (e.g. diabetes, obesity, medications). See triglycerides for more.
    • ASCVD risk ≥ 7.5%
      • If triglycerides persistently elevated after lifestyle modification and risk factor treatment, consider initiating or intensifying statin therapy
Age 40 - 75 with severe hypertriglyceridemia
  • Step 1: Estimate 10-year ASCVD risk (AHA/ACC risk calculator)
  • Step 2:
    • All patients
      • Lifestyle modification (very low-fat diet, avoidance of refined carbohydrates and alcohol, consumption of omega-3 fatty acids)
      • Risk factor treatment (e.g. diabetes, obesity, medications). See triglycerides for more.
      • Consider fibrate therapy. Triglyceride levels ≥ 1000 mg/dl increase the risk of pancreatitis.
    • ASCVD risk ≥ 7.5%
      • Initiate statin therapy


  • Reference [5]
AHA 2018 CAC Treatment Recommendations
Intermediate and borderline risk patients (see primary prevention above)
  • CAC score of zero: it is reasonable to withhold statin therapy and reassess in 5 to 10 years, as long as higher risk conditions are absent (diabetes mellitus, family history of premature CHD, cigarette smoking)
  • CAC score 1 - 99: it is reasonable to initiate statin therapy for patients ≥ 55 years of age
  • CAC score ≥ 100 (or ≥ 75th percentile): it is reasonable to initiate statin therapy

  • Reference [5]
AHA 2018 CAC Screening Recommendations
The AHA states that CAC screening may be appropriate in patients who may benefit from knowing their score is zero. Those patients include the following:
  • Patients reluctant to initiate statin therapy who wish to understand their risk and potential for benefit more precisely
  • Patients concerned about need to reinstitute statin therapy after discontinuation for statin-associated symptoms
  • Older patients (men 55 - 80 years of age; women 60 - 80 years of age) with low burden of risk factors who question whether they would benefit from statin therapy
  • Middle-aged adults (40 - 55 years of age) with 10-year risk of ASCVD of 5% - <7.5% with factors that increase their ASCVD risk, although they are in a borderline risk group