How is atherosclerotic cardiovascular disease (ASCVD) risk stratified in adults, including the risk categories, thresholds, and corresponding statin therapy recommendations?

ASCVD Risk Stratification

Use the ACC/AHA Pooled Cohort Equations to calculate 10-year ASCVD risk in adults aged 40-75 years, then stratify into risk categories (<5%, 5-<7.5%, 7.5-<20%, ≥20%) to guide statin therapy intensity. 1

Risk Assessment Framework

Primary Risk Calculation Tool

• Calculate 10-year ASCVD risk using the Pooled Cohort Equations for all adults aged 40-75 years without clinical ASCVD or diabetes who have LDL-C 70-189 mg/dL. 1 The PCE incorporates age, sex, race (Black vs. White), total cholesterol, HDL-C, systolic blood pressure, antihypertensive medication use, diabetes status, and current smoking. 1

• Assess traditional ASCVD risk factors every 4-6 years in adults aged 20-39 years. 1 For these younger adults, consider estimating lifetime or 30-year ASCVD risk rather than 10-year risk, as 10-year calculations are inherently low despite potentially high lifetime risk. 1, 2

Automatic High-Risk Categories

• Adults with existing clinical ASCVD (acute coronary syndromes, MI, stable/unstable angina, coronary revascularization, stroke, TIA, or peripheral arterial disease) are automatically classified as high risk without requiring risk calculation. 1

• Adults with diabetes mellitus aged 40-75 years are considered higher risk and warrant at least moderate-intensity statin therapy. 1

• Adults with primary LDL-C ≥190 mg/dL (indicating likely familial hypercholesterolemia) require high-intensity statin therapy regardless of calculated risk. 1, 2

• Adults aged ≥65 years with hypertension, those with chronic kidney disease, or those with diabetes are accepted as surrogate markers for higher ASCVD risk. 1

Risk Categories and Statin Recommendations

Low Risk (<5% 10-year ASCVD risk)

• Focus on lifestyle modification without routine statin therapy. 1 Emphasize heart-healthy diet, physical activity, smoking cessation, and weight management. 1

Borderline Risk (5% to <7.5% 10-year ASCVD risk)

• Offer moderate-intensity statin therapy selectively after evaluating risk-enhancing factors and engaging in shared decision-making. 1 This represents a Class IIa recommendation with Level B evidence. 1

• Consider risk-enhancing factors including: family history of premature ASCVD (onset <55 years in male first-degree relative or <65 years in female first-degree relative), persistently elevated LDL-C ≥160 mg/dL, chronic kidney disease, metabolic syndrome, chronic inflammatory conditions (rheumatoid arthritis, psoriasis, HIV), high-sensitivity CRP ≥2 mg/L, or ethnicity associated with higher ASCVD risk. 1, 3

• If uncertainty persists after considering risk-enhancing factors, measure coronary artery calcium (CAC) score to refine risk assessment. 1 A CAC score of 0 supports withholding statin therapy, while CAC ≥100 or ≥75th percentile for age/sex/ethnicity favors statin initiation. 1, 3

Intermediate Risk (7.5% to <20% 10-year ASCVD risk)

• Initiate moderate-to-high intensity statin therapy (Class I recommendation, Level A evidence). 1, 3 This represents the strongest evidence base for primary prevention statin therapy. 3

• Use moderate-intensity statins (atorvastatin 10-20 mg, rosuvastatin 5-10 mg, or simvastatin 20-40 mg daily) targeting 30-50% LDL-C reduction. 2, 3

• Consider CAC scoring when treatment decisions remain uncertain despite calculated intermediate risk. 1, 3 CAC = 0 with event rate of 4.6% may support deferring statin therapy, while CAC > 0 with event rate of 10.4% strongly supports statin initiation. 1

High Risk (≥20% 10-year ASCVD risk)

• Initiate high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) targeting ≥50% LDL-C reduction. 1, 2, 3

• CAC scoring does not alter treatment recommendations in this group, as statins are indicated regardless of CAC results. 1

Special Populations

Diabetes Mellitus

• Initiate moderate-intensity statin therapy for all adults aged 40-75 years with diabetes (Class I recommendation, Level A evidence). 1

• Use high-intensity statin therapy for adults aged 40-75 years with diabetes and estimated 10-year ASCVD risk ≥7.5% (Class IIa recommendation, Level B evidence). 1

• For adults with diabetes aged <40 or >75 years, evaluate potential ASCVD benefits, adverse effects, and patient preferences when deciding on statin therapy. 1

Young Adults (Age <40 years)

• Estimate lifetime ASCVD risk rather than 10-year risk, as 10-year calculations are inherently low despite potentially high lifetime risk. 1, 2

• Initiate immediate statin therapy for LDL-C ≥190 mg/dL without further risk assessment, as this indicates familial hypercholesterolemia. 2

• Consider statin therapy for moderately elevated LDL-C (≥160 mg/dL) in the context of very high lifetime ASCVD risk, particularly with clustering of multiple traditional risk factors. 2

Older Adults (Age >75 years)

• The PCE are validated only for adults aged 40-79 years. 1 Clinical judgment is required for adults >79 years, weighing potential benefits against life expectancy, comorbidities, and patient preferences. 1

Shared Decision-Making Process

Before initiating statin therapy, engage in a clinician-patient discussion addressing: 1, 3

• Potential ASCVD risk-reduction benefits: Approximate absolute risk reduction by multiplying estimated 10-year ASCVD risk by anticipated relative risk reduction (~30% for moderate-intensity or ~45% for high-intensity statin therapy). 1, 3

• Potential adverse effects: Excess diabetes risk (~0.1 cases per 100 individuals per year with moderate-intensity statins, ~0.3 cases per 100 with high-intensity statins), muscle symptoms, and drug-drug interactions. 1, 3

• Heart-healthy lifestyle modifications as the foundation of ASCVD prevention. 1

• Patient preferences and values regarding preventive medication use. 1, 3

Important Caveats

PCE Limitations

• The PCE may overestimate risk in certain contemporary populations, particularly among Hispanic and East Asian adults. 1 Recent data suggest the PREVENT equations provide better calibration and may reduce overestimation. 4, 5

• The PCE may underestimate risk in adults with chronic inflammatory conditions, HIV, chronic kidney disease, or South Asian ethnicity. 1

• The PCE were validated in White and Black U.S. adults but have uncertain accuracy in other racial/ethnic groups. 1

Risk-Enhancing Factors

When calculated risk falls in borderline or intermediate categories and treatment decisions remain uncertain, consider additional factors: 1, 3

• Family history of premature ASCVD (most useful in younger individuals) 1
• Persistently elevated LDL-C ≥160 mg/dL 1
• Metabolic syndrome 1, 3
• Chronic kidney disease (eGFR <60 mL/min/1.73m²) 1, 3
• Chronic inflammatory conditions (rheumatoid arthritis, psoriasis, HIV) 1, 3
• High-sensitivity CRP ≥2 mg/L (most useful in older individuals) 1
• Ankle-brachial index <0.9 (most useful in older individuals) 1
• Lipoprotein(a) ≥50 mg/dL 1
• Apolipoprotein B ≥130 mg/dL 1
• Premature menopause (<40 years) or pregnancy complications 1

Coronary Artery Calcium Scoring

CAC scoring provides objective atherosclerosis burden assessment when risk-based decisions remain uncertain: 1, 3

• CAC = 0: Withhold statin therapy and reassess in 5-10 years (unless diabetes, family history of premature CHD, or current smoking present). 1, 3

• CAC 1-99: Consider moderate-intensity statin therapy, particularly if age 55-75 years. 1

• CAC ≥100 or ≥75th percentile for age/sex/ethnicity: Initiate statin therapy and reclassify to higher risk. 1, 3

• CAC ≥300 Agatston units: Strong indication for statin therapy. 1

Note that CAC is often zero in young adults even with high lifetime risk, limiting its utility in this population. 2

European Approach

The ESC/ESH guidelines use a different framework with four risk categories based on 10-year CVD mortality (not total ASCVD events) using the SCORE risk estimator, with emphasis on hypertension-mediated organ damage assessment. 1 This approach is less applicable to U.S. populations.