Non-HDL Cholesterol and Lipid Profile Ratios: Cardiovascular Risk Assessment
Non-HDL cholesterol is a superior predictor of cardiovascular disease compared to LDL cholesterol alone and should be routinely used to assess atherogenic burden, particularly when triglycerides are elevated. 1
What Non-HDL Cholesterol Measures
Non-HDL cholesterol (calculated as total cholesterol minus HDL cholesterol) represents a comprehensive measure of all cholesterol carried in atherogenic, apolipoprotein B-containing particles, including LDL, VLDL, IDL, remnant lipoproteins, and lipoprotein(a). 1 This makes it a more complete assessment of atherogenic burden than LDL cholesterol alone. 1
Key Advantages Over LDL Cholesterol
Non-HDL cholesterol can be measured in the non-fasting state, eliminating the need for prolonged fasting and making it more practical for clinical use. 1
It does not depend on fasting triglyceride concentrations and remains accurate even when triglycerides are elevated, unlike calculated LDL cholesterol which becomes unreliable at high triglyceride levels. 1
Non-HDL cholesterol captures remnant lipoproteins and other atherogenic particles that are missed by LDL cholesterol measurement alone, particularly important in patients with hypertriglyceridemia. 1
It requires no additional cost as it is calculated directly from the standard lipid panel. 2
Predictive Value for Cardiovascular Events
Non-HDL cholesterol demonstrates stronger associations with cardiovascular outcomes than LDL cholesterol across multiple populations. 1
In the Lipid Research Clinics Follow-Up Study, non-HDL cholesterol levels were strongly predictive of CVD mortality after 19 years of follow-up. 1
Non-HDL cholesterol correlates with coronary calcification, CVD progression, fatty streaks, and raised lesions in coronary arteries. 1
Predictive value has been demonstrated in both men and women, across all age and ethnic groups, and with or without pre-existing CVD. 1
In the Multinational Cardiovascular Risk Consortium study of 398,846 individuals, 30-year cardiovascular disease event rates increased progressively from 7.7% for non-HDL cholesterol <2.6 mmol/L to 33.7% for ≥5.7 mmol/L in women (12.8% to 43.6% in men). 3
Non-HDL cholesterol was superior to LDL cholesterol in predicting CHD events in the Health Professionals Follow-up Study, Framingham Heart Study, and Women's Health Study. 1
Clinical Treatment Targets
The ATP III guidelines recommend non-HDL cholesterol as a secondary treatment target when triglycerides are ≥200 mg/dL, with the target set 30 mg/dL higher than the corresponding LDL cholesterol goal. 1
Specific Target Thresholds
For patients with 0-1 risk factors: Non-HDL cholesterol goal is 190 mg/dL (LDL goal + 30 mg/dL). 1
For patients with 2+ risk factors: Non-HDL cholesterol goal is 160 mg/dL (LDL goal + 30 mg/dL). 1
For patients with CVD or CVD risk equivalents: Non-HDL cholesterol goal is 130 mg/dL (LDL goal + 30 mg/dL). 1
Treatment Gap
Non-HDL cholesterol remains significantly undertreated in clinical practice. In the NEPTUNE II survey, only 27% of high-risk patients with CVD risk equivalents achieved their non-HDL cholesterol goal, and NHANES data showed only 37% of high-risk individuals were at goal. 1
Apolipoprotein B: An Alternative Marker
Apolipoprotein B (apo B) provides a direct measure of the number of atherogenic particles since each potentially atherogenic lipoprotein particle (LDL, VLDL, IDL, remnants, Lp(a)) contains exactly one apo B molecule. 1
Apo B Advantages
Apo B has analytical and biological stability and is valid in non-fasting samples. 1, 4
Apo B was superior to LDL cholesterol in predicting CVD events in the TNT and IDEAL trials, where on-treatment apo B better predicted reduced cardiovascular events. 1, 4
Meta-analyses consistently show apo B superior to LDL cholesterol in predicting coronary heart disease events. 1, 4
Apo B Treatment Targets
When apo B measurement is unavailable, non-HDL cholesterol serves as an acceptable surrogate with targets 30 mg/dL higher than LDL cholesterol targets. 5, 6
Lipid Ratios: Total Cholesterol/HDL Ratio
The total cholesterol/HDL cholesterol ratio is a useful predictor of cardiovascular risk, particularly for identifying subclinical atherosclerosis. 7
In a study of 1,624 subjects, total/HDL cholesterol ratio was the best predictor of having intima-media thickness above the 75th percentile (odds ratio 1.21,95% CI 1.09-1.35). 7
This ratio correlates significantly with intima-media thickness (r = 0.23, p < 0.0001), comparable to non-HDL cholesterol correlation. 7
Triglyceride/HDL Ratio
While the American Heart Association statement discusses the triglyceride/HDL ratio as part of assessing atherogenicity in high-triglyceride profiles 1, the evidence provided focuses primarily on non-HDL cholesterol and apo B as the recommended markers for clinical decision-making.
Special Population Considerations
Pediatric Patients
Non-HDL cholesterol is a significant predictor of atherosclerosis in children and adolescents, as powerful as any other lipoprotein measure. 1
Non-HDL cholesterol levels in childhood strongly predict adult levels, making it valuable for early risk assessment. 1
Non-HDL cholesterol can be accurately calculated in the non-fasting state, making it practical for pediatric screening. 1
Patients with Diabetes
In the DECODE study, non-HDL cholesterol predicted 10-year CVD mortality among those with impaired fasting glucose, though not in those with normal fasting glucose. 1
In the BARI-2D study of patients with CVD and diabetes, mean non-HDL cholesterol (131±40 mg/dL) was above the recommended goal of 130 mg/dL, indicating undertreatment. 1
Patients with Elevated Triglycerides
When triglycerides are ≥200 mg/dL, non-HDL cholesterol assessment becomes particularly important as it captures remnant lipoproteins that contribute significantly to cardiovascular risk. 1
Remnant cholesterol (essentially equivalent to non-HDL cholesterol minus LDL cholesterol) is a strong causal risk factor for atherosclerotic cardiovascular disease. 1
Clinical Implementation
Non-HDL cholesterol should be reported on all routine lipid profiles and used regularly in dyslipidemia management for optimal cardiovascular disease prevention. 2
A meta-analysis supports a 1:1 relationship between percent non-HDL cholesterol lowering and percent cardiovascular risk reduction. 1
Treatment response should be monitored using non-HDL cholesterol when triglycerides are elevated, as it provides more accurate assessment than LDL cholesterol alone. 1
Common Pitfalls to Avoid
Do not rely solely on LDL cholesterol when triglycerides are ≥200 mg/dL, as calculated LDL becomes inaccurate and misses important atherogenic particles. 1
Do not overlook non-HDL cholesterol targets even when LDL cholesterol goals are achieved—many patients remain at elevated risk. 1
Do not assume fasting is required for non-HDL cholesterol assessment; it can be accurately measured in non-fasting samples. 1