What are the recommended LDL‑cholesterol, non‑HDL‑cholesterol, HDL‑cholesterol, and triglyceride targets for adults at low, moderate, high, and very‑high cardiovascular risk, and what is the initial management approach?

Target Cholesterol Values by Cardiovascular Risk Category

For adults at very high cardiovascular risk, target LDL-cholesterol <55 mg/dL (or <70 mg/dL with at least 50% reduction from baseline); for high-risk patients, target LDL-cholesterol <70 mg/dL (or <100 mg/dL); for moderate-risk patients, target LDL-cholesterol <100 mg/dL; and initiate high-intensity statin therapy immediately in very high-risk patients regardless of baseline LDL-cholesterol levels. 1, 2

Risk Stratification Framework

Very High-Risk Patients include those with: 1, 2

• Documented atherosclerotic cardiovascular disease (prior MI, stroke, peripheral arterial disease)
• Diabetes with target organ damage
• Severe chronic kidney disease (eGFR <30 mL/min)
• Familial hypercholesterolemia plus a major cardiovascular risk factor
• Recurrent vascular events within 2 years despite optimal therapy

High-Risk Patients include those with: 1, 2

• Multiple cardiovascular risk factors without established disease
• Diabetes without target organ damage
• Target organ damage from hypertension
• Moderate chronic kidney disease (eGFR 30-59 mL/min)
• 10-year cardiovascular risk ≥20% by Framingham scoring

Moderate-Risk Patients include those with: 1, 2

• 2 or more major risk factors (smoking, hypertension, low HDL-cholesterol, family history of premature CHD, age >45 years for men or >55 years for women)
• 10-year cardiovascular risk 10-20%

Specific LDL-Cholesterol Targets

Very High-Risk Patients

• Primary target: LDL-cholesterol <55 mg/dL 1, 2
• Alternative target for recurrent events: LDL-cholesterol <40 mg/dL 2
• If baseline LDL-cholesterol is 70-135 mg/dL: achieve at least 50% reduction 1, 2
• If baseline LDL-cholesterol ≥130 mg/dL: achieve at least 30-40% reduction 1

High-Risk Patients

• Primary target: LDL-cholesterol <70 mg/dL 1, 2
• Alternative acceptable target: LDL-cholesterol <100 mg/dL 3
• If baseline LDL-cholesterol is 100-200 mg/dL: achieve at least 50% reduction 3

Moderate-Risk Patients

• Primary target: LDL-cholesterol <100 mg/dL 1, 2
• Alternative acceptable target: LDL-cholesterol <130 mg/dL 3

Secondary Lipid Targets

Non-HDL-Cholesterol Targets (when triglycerides 200-499 mg/dL)

• Very high-risk: Non-HDL-cholesterol <85 mg/dL (30 mg/dL above LDL target) 3
• High-risk: Non-HDL-cholesterol <100 mg/dL 3
• Moderate-risk: Non-HDL-cholesterol <130 mg/dL 3

HDL-Cholesterol Considerations

• Low HDL-cholesterol is defined as <40 mg/dL in men 3
• Target HDL-cholesterol >40 mg/dL in men, >50 mg/dL in women 3
• HDL-cholesterol ≥60 mg/dL counts as a "negative" risk factor 3

Triglyceride Targets

• Optimal triglycerides: <150 mg/dL 3
• If triglycerides ≥500 mg/dL: prioritize triglyceride lowering before LDL-cholesterol therapy 3

Initial Management Algorithm

Step 1: Immediate Statin Initiation for Very High-Risk Patients

• Start high-intensity statin therapy immediately (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) regardless of baseline LDL-cholesterol 2
• Consider upfront combination therapy with statin plus ezetimibe if baseline LDL-cholesterol is very high 2

Step 2: Therapeutic Lifestyle Changes for All Patients

• Initiate therapeutic lifestyle changes simultaneously with pharmacotherapy in high and very high-risk patients 1, 2
• Focus on reduction of saturated fat and cholesterol intake, weight loss if indicated, increased dietary fiber, and physical activity 3

Step 3: Reassess and Intensify Therapy at 4-6 Weeks

• If LDL-cholesterol remains above goal after 4-6 weeks on statin monotherapy: add ezetimibe (reduces LDL-cholesterol by up to 47%) 2
• If still not at goal after statin plus ezetimibe: add PCSK9 inhibitor (alirocumab, evolocumab, or inclisiran) or bempedoic acid 2

Step 4: Address Secondary Targets if Primary Goal Achieved

• If triglycerides remain 200-499 mg/dL after achieving LDL-cholesterol goal: target non-HDL-cholesterol 3
• Consider fibrate or niacin therapy for persistent hypertriglyceridemia, though combination therapy with statins has not been evaluated in outcomes studies 3

Critical Implementation Points

Measurement Accuracy

• When LDL-cholesterol is <70 mg/dL, use the Martin/Hopkins method or Sampson equation instead of the Friedewald equation for accurate calculation 1

Safety Considerations

• There is no established lower safety threshold for LDL-cholesterol; trials demonstrate continued cardiovascular benefit without significant adverse effects at LDL-cholesterol levels as low as 30 mg/dL 1
• The concept of "the lower, the better" is supported by consistent evidence showing no harm threshold 1

Common Pitfalls to Avoid

• Do not use the outdated LDL-cholesterol target of <100 mg/dL for very high-risk patients; this target is ineffective and lacks credibility 4
• Do not rely solely on percentage reductions in LDL-cholesterol for patients with baseline LDL-cholesterol <140 mg/dL; absolute targets are more effective 4
• Ensure discharge communication includes specific LDL-cholesterol goals and escalation instructions to maintain continuity between secondary and primary care 2

Antiplatelet Therapy

• Aspirin 75-162 mg daily is recommended for primary prevention in patients with diabetes at increased cardiovascular risk (age ≥40 years or additional risk factors) 3