Non-HDL Cholesterol Guidelines for High-Risk Adults
For adults at high cardiovascular risk, non-HDL cholesterol should be targeted to <130 mg/dL when triglycerides are ≥200 mg/dL, which is 30 mg/dL above the LDL-C goal of <100 mg/dL. 1, 2
Understanding Non-HDL Cholesterol as a Treatment Target
Non-HDL cholesterol represents the total atherogenic cholesterol burden, capturing all lipoproteins except HDL—including LDL, VLDL, remnant lipoproteins, and lipoprotein(a)—making it a powerful independent predictor of cardiovascular events that becomes particularly valuable when triglycerides exceed 200 mg/dL. 2, 3, 4
Non-HDL cholesterol is designated as a secondary treatment target, but only becomes relevant after LDL-C is at goal and when triglycerides remain elevated above 200 mg/dL. 1
Risk-Stratified Non-HDL Cholesterol Goals
The treatment targets are consistently set 30 mg/dL higher than corresponding LDL-C goals across all risk categories:
High-risk patients (≥2 risk factors with 10-year CHD risk >20%): Non-HDL-C goal <130 mg/dL (corresponding to LDL-C <100 mg/dL) 1, 2
Intermediate-risk patients (≥2 risk factors with 10-year CHD risk 10-20%): Non-HDL-C goal <160 mg/dL (corresponding to LDL-C <130 mg/dL) 1, 2
Lower-risk patients (≤1 risk factor): Non-HDL-C goal <190 mg/dL (corresponding to LDL-C <160 mg/dL) 1, 2
Treatment Algorithm for Elevated Non-HDL Cholesterol
Step 1: Initiate Therapeutic Lifestyle Changes
Begin with dietary modifications including saturated fat reduction to <7% of total calories, dietary cholesterol to <200 mg/day, and complete elimination of trans fatty acids. 2
Step 2: Statin Therapy Based on Risk Category
- High-risk patients: Initiate statin therapy simultaneously with lifestyle changes, targeting 30-40% LDL-C reduction or >50% reduction if aiming for LDL-C <70 mg/dL 2
- Moderate-intensity statins (atorvastatin 10-20 mg or rosuvastatin 5-10 mg daily) provide 30-50% LDL-C reduction and simultaneously reduce triglycerides by 10-30% 5, 6
Step 3: Reassess and Intensify if Needed
Reassess fasting lipid panel 4-12 weeks after initiating or adjusting therapy. 2 If non-HDL-C remains above goal after statin optimization, maximize statin therapy before considering add-on agents, as statins lower both LDL-C and non-HDL-C proportionally. 7
Step 4: Add-On Therapy for Persistent Elevation
- For very high triglycerides (≥500 mg/dL): Initiate fibrate or niacin therapy before LDL-lowering therapy, then treat LDL-C to goal after triglyceride reduction 2
- For persistent elevation with moderate triglycerides: Consider adding ezetimibe for an additional 18-25% LDL-C reduction with proven cardiovascular benefit 7
- For persistent low HDL-C and elevated triglycerides: Fenofibrate is preferred over gemfibrozil when combining with statins to minimize myopathy risk 7
Critical Safety Considerations
Avoid high-dose statin plus fibrate combinations, as this significantly increases myopathy risk; use lower statin doses with this combination. 2
Monitor liver function and creatine kinase when using statins, and instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. 2, 6
Never substitute over-the-counter or dietary supplement niacin for prescription niacin—use prescription niacin only when indicated. 2
Important Context from 2013 ACC/AHA Guidelines
While the 2013 ACC/AHA cholesterol guidelines moved away from specific LDL-C and non-HDL-C treatment targets in favor of fixed-intensity statin therapy for defined benefit groups, 1 the earlier ATP III framework for non-HDL-C targets remains clinically relevant for patients with elevated triglycerides where residual risk persists despite statin therapy. 1 The 2013 guidelines found insufficient RCT evidence to support titrating therapy to specific cholesterol targets, but this does not negate the prognostic value of non-HDL-C as a risk marker. 1
For primary prevention in adults aged 40-75 years with one or more CVD risk factors and 10-year ASCVD risk ≥7.5%, moderate- to high-intensity statin therapy is recommended regardless of baseline cholesterol levels. 1