What is the role of identifying and addressing risk enhancers in the management of hyperlipidemia?

Risk Enhancers in Hyperlipidemia Management

Risk enhancers are specific clinical factors that, when present, should prompt more aggressive lipid-lowering therapy by identifying patients at higher cardiovascular risk than traditional risk calculators suggest. 1

What Risk Enhancers Are

Risk enhancers are clinical characteristics that help refine cardiovascular risk assessment beyond standard 10-year ASCVD risk calculations. According to KDIGO guidelines, ASCVD risk enhancers include chronic inflammatory conditions such as systemic lupus erythematosus, rheumatoid arthritis, history of preeclampsia, early menopause, South Asian ancestry, chronic kidney disease, and HIV/AIDS. 1

Reduced eGFR (<60 mL/min/1.73 m²) and albuminuria (ACR >30 mg/g) are independently associated with elevated ASCVD risk and function as important risk enhancers. 1 Additionally, persistently elevated nonfasting triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor. 1

How Risk Enhancers Guide Treatment Decisions

In Primary Prevention with Diabetes

For adults aged 40-75 years with diabetes without clinical ASCVD, the presence of diabetes-specific risk enhancers should prompt consideration of high-intensity statin therapy even when 10-year ASCVD risk is <20%. 1 The treatment algorithm works as follows:

• If 10-year risk ≥7.5% OR diabetes-specific risk enhancers are present: Increase to high-intensity statin therapy 1
• If 10-year risk ≥20%: Target ≥50% LDL-C reduction (and non-HDL-C <100 mg/dL) or LDL-C <70 mg/dL on maximally-tolerated statin therapy 1
• Consider ezetimibe if goals not met despite optimized statin therapy 1

In Glomerular Disease

When assessing ASCVD risk in patients with glomerular disease, clinicians should evaluate LDL-C, Apo B, triglyceride and Lp(a) levels, age group, AND ASCVD risk enhancers together to determine appropriate statin dosage intensity. 1 This comprehensive assessment ensures that patients with chronic kidney disease receive appropriately aggressive lipid management.

Clinical Application Algorithm

The presence of risk enhancers should shift treatment decisions toward more intensive therapy:

1. Calculate baseline 10-year ASCVD risk 1
2. Identify presence of risk enhancers (chronic inflammatory conditions, CKD, albuminuria, persistently elevated triglycerides ≥175 mg/dL, diabetes-specific factors) 1
3. If risk enhancers present in borderline risk patients (5-7.5%): Favor statin initiation 1
4. If risk enhancers present in intermediate risk patients (7.5-20%): Consider high-intensity statin therapy 1
5. Align statin dosage intensity to the enhanced risk level, not just the calculated risk 1

Important Caveats

The accuracy of ASCVD risk estimators has not been well validated for adults with chronic inflammatory disorders or HIV. 1 This means clinicians must exercise clinical judgment when applying risk calculators to these populations, and the presence of these conditions as risk enhancers becomes even more critical in treatment decisions.

Risk enhancers are particularly important in patients with moderate hypertriglyceridemia (150-499 mg/dL) and borderline to intermediate ASCVD risk, where their presence tips the balance toward initiating or intensifying statin therapy. 1