Who are considered high risk where a target Low-Density Lipoprotein (LDL) < 70 mg/dL should be considered?

High-Risk Patients Who Should Target LDL < 70 mg/dL

Patients considered high-risk who should target LDL < 70 mg/dL include those with established atherosclerotic cardiovascular disease, multiple major risk factors, severe risk factors, or specific comorbidities that significantly increase cardiovascular risk. 1

Very High-Risk Categories

Established Cardiovascular Disease

• Secondary prevention patients with:
  • History of multiple major ASCVD events 1
  • Major ASCVD event plus multiple high-risk conditions 1
  • Acute coronary syndromes 1
  • Documented coronary heart disease (CHD) 1
  • Peripheral artery disease (PAD) 1
  • Ischemic stroke 1
  • Documented atherosclerosis on imaging (significant plaque on coronary angiography or CT angiography showing ≥50% stenosis in 2 major epicardial arteries) 1

Diabetes Mellitus with Additional Risk Factors

• Diabetes plus any of the following:
  • Long duration of diabetes 1
  • Albuminuria 1
  • eGFR <60 mL/min/1.73 m² 1
  • Retinopathy 1
  • Neuropathy 1
  • Ankle-brachial index (ABI) <0.9 1

Multiple Risk Factors or Severe Risk Factors

• Severe hypercholesterolemia (LDL-C ≥190 mg/dL) 1
• Multiple major risk factors, especially with:
  • Family history of premature ASCVD 1
  • Persistent elevated triglycerides ≥200 mg/dL 1
  • High-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L 1
  • Lipoprotein(a) >50 mg/dL 1
  • Apolipoprotein B >130 mg/dL 1
• Severe and poorly controlled risk factors, especially continued cigarette smoking 1
• Metabolic syndrome with multiple components 1

Imaging and Other Risk Enhancers

• Coronary artery calcium (CAC) score >100 1
• Carotid or femoral plaque on arterial ultrasound 1
• ABI <0.9 or >1.4 1

Special Populations

• Chronic kidney disease (eGFR 15-59 mL/min, not on dialysis or transplant) 1
• Inflammatory diseases (e.g., rheumatoid arthritis, lupus) 1
• HIV infection or on HIV treatment 1
• Female-specific risk factors:
  • History of preeclampsia 1
  • Premature menopause (<40 years) 1
• South Asian ancestry 1

Practical Considerations

Treatment Approach

• Start with high-intensity statin therapy to achieve at least a 50% reduction in LDL-C 2
• If LDL-C remains ≥70 mg/dL despite maximally tolerated statin therapy, consider adding ezetimibe 1
• For very high-risk patients who still don't achieve target, consider PCSK9 inhibitors 1

Monitoring and Follow-up

• Check lipid panel 4-12 weeks after initiating therapy to assess response 2
• Monitor for side effects, particularly muscle symptoms and liver function abnormalities 2

Common Pitfalls to Avoid

1. Underestimating risk status - many high-risk patients are not identified correctly 3, 4
2. Inadequate statin dosing - suboptimal uptitration of statin dose is common 5
3. Infrequent lipid monitoring - more frequent LDL-C measurements are associated with better goal attainment 6
4. Underutilization of combination therapy - ezetimibe and other non-statin therapies are used infrequently despite evidence supporting their use 4
5. Stopping at the minimum goal - achieving LDL-C <70 mg/dL may provide additional benefit over just reaching <100 mg/dL in very high-risk patients 5

Despite clear guidelines, studies show that less than 50% of high-risk patients achieve the recommended LDL-C goal of <70 mg/dL 3, highlighting the need for more aggressive lipid management in these populations.