Diagnostic Criteria for Hyperlipidemia
Hyperlipidemia is diagnosed using fasting lipid panel measurements with specific thresholds: total cholesterol (TC) ≥240 mg/dL or ≥8.0 mmol/L (310 mg/dL) for severe cases, LDL-cholesterol calculated by Friedewald formula (unless triglycerides >400 mg/dL), and triglycerides classified as mild (150-199 mg/dL), moderate (200-999 mg/dL), severe (1,000-1,999 mg/dL), or very severe (≥2,000 mg/dL). 1
Required Laboratory Testing
Primary Lipid Panel
The baseline evaluation must include 1:
- Total cholesterol (TC)
- Triglycerides (TG) - requires 12-hour fasting
- HDL-cholesterol
- LDL-cholesterol - calculated using Friedewald formula: LDL-C = TC - HDL-C - TG/5 (mg/dL) or TG/2.2 (mmol/L)
- Non-HDL cholesterol (TC minus HDL-C)
- TC/HDL-C ratio
Critical Calculation Limitations
The Friedewald formula cannot be used when 1:
- Triglycerides ≥400 mg/dL (≥4.5 mmol/L) - requires direct LDL measurement
- Non-fasting samples
- In these cases, use direct LDL assay or non-HDL cholesterol instead
Diagnostic Thresholds
Hypercholesterolemia
- TC ≥8.0 mmol/L (310 mg/dL) indicates high risk requiring immediate attention regardless of other risk factors 1
- Patients with familial hypercholesterolemia (FH) or familial combined hyperlipidemia (FCH) are automatically high risk 1
Hypertriglyceridemia Classification
The Endocrine Society defines 1, 2:
- 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)
Severe and very severe levels significantly increase acute pancreatitis risk 1, 2
Essential Diagnostic Steps
Fasting Requirements
- 12-hour fasting is mandatory for accurate triglyceride measurement 1
- TC, HDL-C, and apolipoprotein B can be measured non-fasting 1
- Non-fasting samples may be used for screening, but fasting confirmation is required for diagnosis 1
Exclude Secondary Causes First
Before diagnosing primary hyperlipidemia, evaluate for 1, 3, 4:
- Diabetes mellitus (uncontrolled)
- Hypothyroidism (most common secondary cause after diet)
- Excessive alcohol intake
- Medications: thiazides, beta-blockers, estrogens, oral contraceptives, isotretinoin, corticosteroids, bile acid-binding resins, protease inhibitors, immunosuppressants, antipsychotics, cyclosporine
- Renal disease (GFR <60 mL/min/1.73 m²)
- Liver disease
- Pregnancy (especially third trimester)
- Autoimmune disorders
- Obesity and physical inactivity
Adjust for Treatment Effects
When patients are already on lipid-lowering therapy 1:
- Adjust LDL-cholesterol values for statins, ezetimibe, and PCSK9 inhibitors
- If diagnosis uncertain, repeat measurement after full recovery from acute illness
- Pretreatment values are most reliable for diagnosis
Distinguishing Primary Hyperlipidemia Types
Familial Hypercholesterolemia (FH)
- Elevated LDL-cholesterol with normal triglycerides 1
- Physical stigmata: tendon xanthomas, xanthelasmas, premature arcus cornealis
- Family history of premature cardiovascular disease
- Genetic testing confirms diagnosis when available
Familial Combined Hyperlipidemia (FCH)
- Apolipoprotein B >90th percentile (key distinguishing feature) 3
- Multiple lipoprotein abnormalities in first-degree relatives
- Variable lipid phenotypes within same family
Familial Hypertriglyceridemia (FHTG)
- Triglycerides 200-1,000 mg/dL with elevated VLDL 3
- Normal apolipoprotein B levels (distinguishes from FCH)
- Polygenic inheritance pattern
- Usually manifests in adulthood with environmental triggers
Critical Pitfalls to Avoid
Intraindividual Variation
- TC varies 5-10% and triglycerides ≥20% between measurements 1
- Seasonal variation exists (higher TC and HDL-C in winter)
- Obtain multiple measurements before making definitive diagnosis
Hypertriglyceridemia Confounding
- When triglycerides are 400-850 mg/dL and FH suspected, use novel calculation equations or direct LDL assay 1
- With very severe hypertriglyceridemia, therapeutically lower triglycerides first, then reassess for underlying hypercholesterolemia 1