Diagnosis of Hyperlipidemia and Dyslipidemia: Laboratory Thresholds and Criteria
Hyperlipidemia or dyslipidemia is diagnosed through specific lipid profile testing with established thresholds: total cholesterol ≥200 mg/dL, LDL-C ≥130 mg/dL, triglycerides ≥150 mg/dL, or HDL-C <40 mg/dL in men or <50 mg/dL in women. These measurements should be obtained after excluding secondary causes and typically require fasting samples for accurate triglyceride assessment 1.
Basic Lipid Profile Components and Collection
The baseline lipid evaluation should include:
- Total cholesterol (TC)
- Triglycerides (TG)
- High-density lipoprotein cholesterol (HDL-C)
- Low-density lipoprotein cholesterol (LDL-C)
- Non-HDL cholesterol (calculated as TC minus HDL-C)
Fasting vs. Non-fasting
- For most screening purposes, non-fasting samples are acceptable 1, 2
- Fasting (12 hours) is primarily required for accurate triglyceride assessment
- When TG levels are elevated (≥4.5 mmol/L or ≥400 mg/dL), fasting samples are necessary for accurate LDL-C calculation 1
LDL-C Calculation
- Typically calculated using the Friedewald formula:
- In mmol/L: LDL-C = TC - HDL-C - TG/2.2
- In mg/dL: LDL-C = TC - HDL-C - TG/5
- Direct measurement is required when TG ≥400 mg/dL 1
Diagnostic Thresholds for Adults
Hypercholesterolemia
- Borderline high: TC 200-239 mg/dL (5.2-6.2 mmol/L)
- High: TC ≥240 mg/dL (≥6.2 mmol/L)
- Very high: TC ≥310 mg/dL (≥8.0 mmol/L) - requires special attention 1
LDL Cholesterol
- Near optimal: 100-129 mg/dL (2.6-3.3 mmol/L)
- Borderline high: 130-159 mg/dL (3.4-4.1 mmol/L)
- High: 160-189 mg/dL (4.1-4.9 mmol/L)
- Very high: ≥190 mg/dL (≥4.9 mmol/L)
Hypertriglyceridemia 1
- Mild: 150-199 mg/dL (1.7-2.3 mmol/L)
- Moderate: 200-999 mg/dL (2.3-11.3 mmol/L)
- Severe: 1,000-1,999 mg/dL (11.3-22.6 mmol/L)
- Very severe: ≥2,000 mg/dL (≥22.6 mmol/L)
HDL Cholesterol
- Low (increased risk): <40 mg/dL (<1.0 mmol/L) in men, <50 mg/dL (<1.3 mmol/L) in women
- Optimal: ≥60 mg/dL (≥1.6 mmol/L)
Non-HDL Cholesterol
- Elevated: ≥145 mg/dL (≥3.8 mmol/L)
Special Considerations
Familial Hypercholesterolemia (FH)
FH should be suspected in adults with 1:
- LDL-C ≥190 mg/dL (≥4.9 mmol/L)
- Family history of premature CVD
- Presence of tendon xanthomas or premature arcus cornealis
Children and Adolescents
For children and adolescents, FH should be considered with 1:
- LDL-C >4.9 mmol/L (>190 mg/dL) on two occasions
- LDL-C >4.0 mmol/L (>160 mg/dL) with family history of high LDL-C or premature CVD
- LDL-C >3.5 mmol/L (>135 mg/dL) with a parent having a pathogenic gene variant for FH
Diabetes-Specific Targets 1
For patients with diabetes:
- LDL-C goal: <100 mg/dL (<2.6 mmol/L)
- Triglycerides goal: <150 mg/dL (<1.7 mmol/L)
- HDL-C goal: >40 mg/dL (>1.0 mmol/L) in men, >50 mg/dL (>1.3 mmol/L) in women
Clinical Pitfalls and Caveats
Secondary causes must be excluded before diagnosing primary dyslipidemia:
- Untreated diabetes
- Hypothyroidism
- Obstructive liver disease
- Chronic kidney disease
- Medications (thiazides, beta-blockers, estrogens, corticosteroids)
- Excessive alcohol consumption
Intraindividual variation in lipid levels:
- TC: 5-10% variation
- TG: ≥20% variation, particularly in hypertriglyceridemia
- Seasonal variation with higher TC and HDL-C during winter 1
Friedewald formula limitations:
- Inaccurate with TG ≥400 mg/dL
- Assumes constant cholesterol/TG ratio in VLDL
- Not valid for non-fasting samples 1
Acute illness can affect lipid levels; measurements should be repeated after full recovery 1
Medication effects should be considered when interpreting results; LDL-C should be adjusted for statin use and other lipid-lowering therapies 1
By following these diagnostic criteria and being aware of the potential pitfalls, clinicians can accurately diagnose dyslipidemia and initiate appropriate treatment to reduce cardiovascular risk.