CHOLESTEROL GUIDELINES

• 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

• 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

• 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 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)

Any patient with diabetes

• See diabetes recommendations below

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
• If CAC score is available: see CAC recommendations
• Intermediate risk: if risk enhancers are present, start moderate-intensity statin to reduce LDL by 30 - 49%
• If CAC score is available: see CAC recommendations
• 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

• 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/ethnicities (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

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

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

• 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

• 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)

• 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

Age 20 - 39 years

• If diabetes-specific risk enhancers are present, it may be reasonable to initiate a statin

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

• 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

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

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.
• ASCVD present: High-intensity statin recommended. If LDL ≥ 70 mg/dl despite maximally tolerated statin, consider adding ezetimibe or PCSK9 inhibitor

• 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)

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

Triglyceride ranges

• Normal: < 150 mg/dl
• Mild hypertriglyceridemia: 150 - 174 mg/dl
• Moderate hypertriglyceridemia: 175 - 499 mg/dl
• Severe hypertriglyceridemia: ≥ 500 mg/dl

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

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

• 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