What are the management strategies for patients at risk of Atherosclerotic Cardiovascular Disease (ASCVD)?

ASCVD Risk Assessment and Management

For adults aged 40-75 years without established ASCVD or diabetes, calculate 10-year ASCVD risk using the Pooled Cohort Equations every 4-6 years, then stratify patients into low (<5%), borderline (5-<7.5%), intermediate (7.5-19.9%), or high (≥20%) risk categories to guide treatment decisions. 1, 2

Risk Calculation Framework

Primary risk assessment:

• Use the Pooled Cohort Equations for all adults 40-75 years with LDL-C between 70-189 mg/dL who lack clinical ASCVD or diabetes 2
• Reassess risk every 4-6 years in patients found to be at low risk 3
• For younger adults (20-59 years), consider calculating 30-year or lifetime risk to motivate lifestyle changes, but do not use long-term risk to guide pharmacologic therapy decisions 3

Risk-Enhancing Factors to Identify

When risk category is uncertain (particularly borderline or intermediate risk), assess for these factors that may tip the balance toward treatment 1, 2:

• Family history of premature ASCVD 2
• Persistently elevated LDL-C ≥160 mg/dL 1, 2
• Chronic kidney disease 1
• Metabolic syndrome (fasting triglycerides ≥150 mg/dL is one criterion) 1
• Chronic inflammatory conditions: rheumatoid arthritis, psoriasis, systemic lupus erythematosus, HIV infection 2
• Women-specific factors: preeclampsia, premature menopause 1
• Biomarkers (if measured): high-sensitivity CRP ≥2 mg/L, lipoprotein(a) >50 mg/dL, apolipoprotein B ≥130 mg/dL 1, 2
• Ankle-brachial index <0.9 1, 2

Management Algorithm by Risk Category

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

• Do not initiate statin therapy unless other specific indications exist 3
• Focus exclusively on lifestyle optimization: Mediterranean or DASH diet, ≥150 minutes/week moderate-intensity exercise (or 75 minutes vigorous), smoking cessation, weight loss if overweight 1, 2
• Reassess in 4-6 years 3

Borderline Risk (5-<7.5%):

• Optimize lifestyle interventions first 1
• Presence of risk-enhancing factors (especially persistent hypertriglyceridemia ≥175 mg/dL) favors early statin initiation 1
• If decision remains uncertain after assessing risk enhancers, obtain coronary artery calcium (CAC) score 1, 3
• CAC = 0 allows deferring statin therapy in most cases 3
• CAC ≥300 Agatston units or ≥75th percentile for age/sex/ethnicity supports statin initiation 2

Intermediate Risk (7.5-19.9%):

• Initiate clinician-patient risk discussion before starting pharmacotherapy 1
• Risk-enhancing factors support statin therapy 1
• If uncertainty persists, CAC scoring is most beneficial in this group 3
• CAC = 0 may allow withholding statin in selected patients 3
• CAC >0 generally supports moderate-intensity statin therapy 2

High Risk (≥20%):

• Initiate high-intensity statin therapy without need for additional risk assessment 1, 2
• Target ≥50% LDL-C reduction 2
• Persistent hypertriglyceridemia in this group supports intensification of statin therapy 1

Special Populations

Diabetes mellitus (without established ASCVD):

• Initiate moderate-intensity statin for all patients 40-75 years with LDL-C 70-189 mg/dL without calculating 10-year risk 2
• Escalate to high-intensity statin if multiple risk factors present or 10-year ASCVD risk ≥7.5% 2
• Target blood pressure <130/80 mmHg if higher cardiovascular risk, <140/90 mmHg if lower risk 2
• Use ACE inhibitors or ARBs as first-line antihypertensive, especially with albuminuria 2

Primary hyperlipidemia (LDL-C ≥190 mg/dL):

• Initiate high-intensity statin immediately without calculating 10-year risk 2
• Target ≥50% LDL-C reduction 2
• If LDL-C remains ≥100 mg/dL on maximally tolerated statin, add ezetimibe 2

Established ASCVD (secondary prevention):

• High-intensity statin for all patients ≤75 years without safety concerns 2
• Moderate-intensity statin for patients >75 years or with safety concerns 2
• If LDL-C remains ≥70 mg/dL on maximally tolerated statin, add ezetimibe or PCSK9 inhibitor 2

Critical Pitfalls to Avoid

• Never initiate statin therapy based solely on age without comprehensive risk assessment 3
• Do not use CAC scoring in low-risk patients where it will not change management 3
• Do not rely on 30-year or lifetime risk calculations to guide pharmacologic decisions in younger adults—these are for motivating lifestyle changes only 3
• Always emphasize lifestyle goals even when prescribing medications—pharmacotherapy does not replace diet, exercise, and smoking cessation 1
• Do not overlook younger adults with low 10-year risk but significant lifetime risk—aggressive lifestyle modification is essential in this group 3