Cardiology

New Lipid Guidelines

Definitions
ASCVD Screening Recommendations (adults)
Lab Testing
Primary Prevention (adults 30 to 79 years)
Risk Enhancers
Secondary Prevention
Lipoprotein Goals
Secondary Causes of Elevated LDL-C
Lipid Lowering Therapies
When to Refer to Specialist
Primary Sources

SUMMARY:

The 2026 ACC/AHA guidelines retire and replace the 2018 ones and specifically address the evaluation, management, and monitoring of individuals with dyslipidemias, including high blood cholesterol, hypertriglyceridemia, and elevated lipoprotein(a). The new guidelines highlight that early and/or prolonged exposure to hypercholesterolemia, and especially LDL-C is an important risk for ASCVD. The guidelines recommend using the newer AHA Predicting Risk of cardiovascular disease EVENTs (PREVENT™) calculator rather than previous ASCVD Risk Calculator to determine which patients are at risk, initiating LDL-lowering therapies as primary prevention in borderline risk patients, considering ApoB testing to improve risk assessment and guide therapy, and measuring Lipoprotein(a) once in all adults’ lifetimes to identify individuals at higher risk of ASCVD.

Definitions

Cardiovascular-kidney-metabolic syndrome (CKM) is a constellation of symptoms including
- Abdominal obesity | Insulin-resistant glucose metabolism | Dyslipidemia | Elevated blood pressures
- Sometimes kidney disease (CKD, microalbuminuria and/or proteinuria)
Major ASCVD Events
- Acute coronary syndromes (ACS) within past 12 months
- History of myocardial infarction (MI)
- History of ischemic stroke
- Symptomatic peripheral artery disease (PAD)
At Very High Risk of ASCVD
- ≥2 major ASCVD events (listed above) or 1 major ASCVD events and ≥ 2 high risk features
  - ≥65 years | Coronary bypass or percutaneous intervention | Current smoker | Diabetes | History of heart failure, HTN | LDL-C ≥100 mg/dL (2.6 mmol/L) despite maximally tolerated statin + ezetimibe
Dyslipidemias
- Elevated blood cholesterol | Hypertriglyceridemia | Elevated Lp(a)
Subclinical atherosclerosis
- Presence of atheromatous disease in ≥1 arterial territories before there are any signs, symptoms, or events attributable to clinically manifest atherosclerotic disease in those territories
Primary prevention
- Prevention and management of ASCVD risk factors early in life
- Statin therapy is the initial drug of choice based on safety, tolerability, efficacy, and cost
Secondary prevention
- Management of lipid levels in individuals with a history of ASCVD events to reduce risk of future events
- Statin therapy is the foundational lipid-lowering treatment due to strong association between LDL-C and ASCVD risk

ASCVD Screening Recommendations (adults)

General population: Begin age 19 years | Screen every 5 years
Adults with ASCVD risk factors: Screen more frequently than every 5 years
Heterozygous familial hypercholesterolemia (HeFH)
- HeFH affects 1 in 250 to 300 adults and is associated with 2- to 4-times higher risk of premature ASCVD
- Consider genetic testing for heterozygous familial hypercholesterolemia (HeFH) in patients with family history of premature ASCVD, if not already done in childhood

Note: Use the new and improved PREVENT-ASCVD equation (‘Learn More – Primary Sources’ Section Below) to estimate 10-year (and 30-year) risk and to guide therapeutic decisions

Lab Testing

General population
- Either a fasting or nonfasting lipid profile is sufficient
- There is only minimal difference in LDL-C between fasting and nonfasting
Fasting lipid profile indicated
- Nonfasting lipid profile reveals a triglyceride (TG) level ≥ 400 mg/dL
- Known/suspected TG metabolism disorder
- Family history of dyslipidemia or premature ASCVD
Non–HDL-C
- Calculated as TC minus HDL-C
- Composite measure of all atherogenic lipoproteins
- Correlates well with levels of apoB, an even better predictor of ASCVD risk than LDL-C
ApoB
- Helpful to measure as a guide for initiation or intensifying lipid-lowering therapies, especially once LDL-C is at goal using a statin
- Predicts ASCVD risk more accurately than LDL-C in cases where LDL-C and apoB provide differing risk estimates
Lp(a)
- Measure at least once for all adults (robust evidence linking higher Lp(a) levels with higher ASCVD risk)

Once lipid-lowering therapies are initiated, clinicians should monitor a lipid profile again in 4 to 12 weeks and then every 6 to 12 months thereafter

Primary Prevention (adults 30 to 79 years)

All Adults Should Have Their 10-Year ASCVD Risk Estimated Using The PREVENT-ASCVD Equation

PREVENT-ASCVD <10%
- Low risk: 0 to 3%
  - LDL <160 mg/dL: Counsel on health behaviors
  - LDL is 160 to 189 mg/dL: Initiate a moderate-intensity statin
- Borderline risk: 3 to <5%
  - After risk-benefit conversation and consideration of risk enhancers (list below), consider initiation of a moderate-intensity statin
  - Measure high-sensitivity CRP: Initiate high intensity statin If ≥2 mg/L x2
- Intermediate risk: 5 to <10%
  - Initiative a moderate-intensity statin
- Goals for ASCVD <10%:
  - LDL‑C <100 mg/dL | Non‑HDL‑C <130 mg/dL
  - TG ≥150 to 499 mg/dL: apoB goal <90 mg/dL
PREVENT-ASCVD ≥10% (High Risk)
- Initiate high-intensity statin with goal of ≥50% LDL-C reduction
- Statin + add ezetimibe if needed to reach lipid goals
- Statin + ezetimibe + add PCSK9 mAb or bempedoic acid if needed
- Goals for ASCVD ≥10%
  - LDL‑C <70 mg/dL | Non‑HDL‑C <100 mg/dL
  - TG ≥150 to 499 mg/dL: apoB goal <70 mg/dL

Risk Enhancers

History of premature ASCVD in a parent or sibling (<55 yo for men, <65 yo for women)
Higher risk ancestry (South Asian, Filipino)
Chronic inflammatory diseases
Lp(a) ≥ 125 nmol/L
HsCRP ≥2 when measured >x1
TG level ≥175 mg/dL (nonfasting) and ≥150 (fasting)
CKM syndrome
LDL-C persistently ≥160 to 189
Non-HDL-C ≥190 to 219 mg/dL
Reproductive risk markers (premature menopause, preeclampsia, gestational diabetes, gestational hypertension, preterm delivery)
High Coronary Artery Calcium Score (see ‘Learn More – Primary Sources’ below)

Secondary Prevention

Lipoprotein Goals

Severe Hypercholesterolemia

No Familial Hypercholesterolemia (FH), ASCVD risk factors or subclinical atherosclerosis
- LDL‑C <100 mg/dL | Non‑HDL‑C <130 mg/dL
FH, ASCVD risk factors or subclinical atherosclerosis present
- LDL‑C <70 mg/dL | Non‑HDL‑C <100 mg/dL
Severe hypercholesterolemia or HeFH with clinical ASCVD
- LDL‑C <55 mg/dL

Diabetes

Initiate a moderate-intensity statin to achieve 30 to 49% LDL-C reduction

No ASCVD risk factors or diabetes-specific risk modifiers
- LDL‑C <100 mg/dL | Non‑HDL‑C <130 mg/dL
- apoB goal <90 mg/dL
ASCVD risk factors or diabetes‑specific risk modifiers present
- LDL‑C <70 mg/dL | Non‑HDL‑C <100 mg/dL
- apoB goal <70 mg/dL

Subclinical Atherosclerosis

CAC 1 to 99 AU and <75% for age/sex/race
- LDL‑C <100 mg/dL | Non‑HDL‑C <130 mg/dL
CAC ≥ 100 to 299 AU or ≥75% for age/sex/race
- LDL‑C <70 mg/dL | Non‑HDL‑C <100 mg/dL
CAC ≥300 to 999 AU
- Optional goal: LDL-C <55 mg/dL | Non-HDL-C <85 mg/dL
- Consider apoB <55 mg/dL
CAC ≥1000 AU
- LDL‑C <55 mg/dL | Non‑HDL‑C <85 mg/dL

Hypertriglyceridemia

Age <50 years, no additional risk enhancers
- LDL‑C <100 mg/dL | Non‑HDL‑C <130 mg/dL
Clinical ASCVD present not very high risk OR age 40 to 75 with ≥ ASCVD risk factor
- LDL‑C <70 mg/dL | Non‑HDL‑C <100 mg/dL
- ApoB <70 mg/dL
Clinical ASCVD at very high risk
- LDL‑C <55 mg/dL | Non‑HDL‑C <85 mg/dL
- ApoB goal <55 mg/dL

Clinical ASCVD

Not at very high risk
- LDL‑C <70 mg/dL | Non‑HDL‑C <100 mg/dL
- Optional goal: LDL‑C <55 mg/dL, non‑HDL‑C <85 mg/dL
- Consider apoB <55 mg/dL
At Very High Risk
- Start a high intensity or maximally-tolerated statin
- If lipid goals (below) not met: add ezetimibe and/or PCSK9 mAb
- If not tolerated: start inclisiran to lower LDL-C
- If goals are still not met: add bempedoic acid
- Goals for Very High Risk of ASCVD
  - LDL‑C <55 mg/dL | Non‑HDL‑C <85 mg/dL
  - ApoB <55 mg/dL

Special Considerations

≥CKD3 and LDL-C of 70 to 189 mg/dL (ages 40 to 75)
- Initiate a moderate-intensity statin +/- ezetimibe
HIV (ages 40 to 75)
- Start a statin to reduce risk of a first ASCVD event
- Check drug interactions to ensure safety with antiretrovirals
>75 years with a life expectancy of >2.5 years
- May be reasonable to initiative a moderate-intensity statin
- If the decision is uncertain, consider obtaining a CAC level to help with the decision
Stop LLT if life expectancy is <1 year
HeFH
- Increases lifetime risk of ASCVD by x 2-4 and the standard ASCVD risk calculators are not applicable
LDL-C ≥190 mg/dL with no secondary cause
- Conduct genetic testing
- Consider genetic testing for individuals with LDL-C of 160-189

Secondary Causes of Elevated LDL-C

Diet: High intake of saturated fat | Trans-fat | Cholesterol | Rapid weight gain or weight loss | Ketosis
Metabolic: Hypothyroidism | Obstructive liver disease | CKD | Nephrotic syndrome | Insulin resistance or DM | Cushing syndrome | Anorexia | Obesity
Drugs: High dose thiazide diuretics | Glucocorticoids | Estrogens | Androgens | Atypical antipsychotics | Cyclosporine
Physiologic: Menopause | Pregnancy

Lipid Lowering Therapies

Lifestyle Management

Dietary supplements are not recommended to lower LDL-C or TG.
Counseling should focus on healthy diet, regular physical activity, maintenance of a healthy weight, adequate sleep, stress management and avoidance of tobacco products.
Diet
- Recommended Diets: Mediterranean diet | DASH diet | Vegetarian diets
- Replace saturated fat with unsaturated fat
- Elevated TG: Counseling should emphasize diets low in added sugars, total fat, and alcohol
- Minimizing intake of simple carbohydrates especially processed carbohydrates, including all added sugars | Results in substantial TG lowering
- Refer to a nutritionist when
  - Fasting TG ≥1000 mg/dL (11.3 mmol/L) or TG ≥150 to 999 mg/dL and features of CKM syndrome
Weight loss
- Medications and therapies should be offered to lower weight by ≥5%
Physical activity
- Recommend ≥150 minutes/week of moderate-to-vigorous intensity aerobic exercise + resistance training 2 days/week

LDL-C-Lowering Medications

HMG-CoA reductase inhibitors (statins)
- Route: oral
- Mechanism: inhibit the enzyme that produces endogenous cholesterol
- First-line therapy for ASCVD risk reduction in nearly all patients
- High-intensity (≥50% reduction in LDL-C)
  - Atorvastatin (80mg daily)
  - Rosuvastatin (40mg daily)
- Medium or low-intensity (≥30 to 49% reduction in LDL-C)
  - Atorvastatin (10 to 40mg daily)
  - Rosuvastatin (5 to 20 mg daily)
  - Fluvastatin (20 to 80mg 1-2x daily)
  - Lovastatin (10 to 80mg 1-2x daily)
  - Pitavastatin (1 to 4mg daily)
  - Pravastatin (10 to 80mg daily)
  - Simvastatin (5 to 40mg daily)
Ezetimibe (10mg daily)
- Route: Oral
- Mechanism: Blocks the sterol transporter protein
- Can reduce LDL-C by 18% alone or by 25% when combined with a statin
PCSK9 inhibitors (monoclonal antibodies)
- Route: Subcutaneous
- Mechanism: Binds PCSK9, decreasing LDL receptor degradation
- Combined with a statin in very high-risk patients for secondary prevention
- Can reduce LDL-C by 45 to 64%
- Agents:
  - Alirocumab (75 to 150mg every 2 weeks OR 300mg every 4 weeks)
  - Evolocumab (140mg every 2 weeks)
Bempedoic acid (180mg daily)
- Route: Oral
- Mechanism: ATP citrate lyase inhibitor, decreases endogenous cholesterol production upstream of HMG-CoA reductase
- Can be used for high-risk primary and secondary prevention
- Can reduce LDL-C as monotherapy (for patients with statin side effects) by 21 to 24%
Inclisiran (284mg initial dose)
- Route: Subcutaneous, administered every 6 months (after initial 2 doses which are 3 months apart)
- Mechanism: Breaks down mRNA for PCSK9, decreasing degradation of LDL receptors
- Reduces LDL-C by 48 to 52%
Bile acid sequestrants
- Route: Oral
- Mechanism: Binds bile acids in gut, interrupting enterohepatic recirculation of bile acids, which increases conversion of cholesterol to bile acids in the liver
- Can be added to statin therapy with benefits being dose-related
- Side effects
  - Can increase serum TG level (avoid if TG ≥300 mg/d)
  - May cause GI side effects, in dose dependent fashion
- Can decrease LDL-C by 10 to 27%
- Agents:
  - Cholestyramine (8 to 16g x1-2 daily)
  - Colesevelam (3.75mg x1-2 daily)
  - Colestipol (2 to 16 g x1-2 daily)

When to Refer to Specialist

Individuals with familial lipid disorders or very high levels of atherogenic lipoproteins or TG
Individuals who have difficulty tolerating standard lipid-lowering medications