Which type of dyslipidemia is characterized by markedly low high‑density lipoprotein (HDL), low‑to‑normal low‑density lipoprotein (LDL), and very high triglycerides?

Dyslipidemia with Very Low HDL, Normal-to-Low LDL, and Very High Triglycerides

The dyslipidemia pattern you describe—markedly low HDL cholesterol, low-to-normal LDL cholesterol, and very high triglycerides—is most characteristic of familial hypertriglyceridemia or severe hypertriglyceridemia syndromes, particularly when triglycerides exceed 1000 mg/dL. 1

Primary Diagnostic Considerations

Familial Hypertriglyceridemia

• This is the most common genetic cause, affecting 5-10% of the population, characterized by triglycerides ranging from 200-1000 mg/dL (or higher with secondary triggers), elevated VLDL, and notably normal apoB levels—distinguishing it from familial combined hyperlipidemia. 1
• The condition results from VLDL overproduction and reduced VLDL catabolism that saturates lipoprotein lipase capacity. 1
• HDL cholesterol is typically low due to enhanced exchange of triglycerides from VLDL into HDL particles. 1
• LDL cholesterol remains normal or low because the metabolic defect primarily affects triglyceride-rich lipoproteins rather than LDL particles. 1

Severe Hypertriglyceridemia (Triglycerides ≥1000 mg/dL)

• When triglycerides exceed 1000 mg/dL, this represents severe hypertriglyceridemia with both increased VLDL and chylomicrons, creating immediate pancreatitis risk. 1, 2
• This can occur with genetic lipoprotein lipase deficiency (homozygous or heterozygous), apolipoprotein CII deficiency, or apolipoprotein AV deficiency. 1
• Chylomicronemia syndrome presents with triglycerides >1000 mg/dL, lipemia retinalis, eruptive xanthomas, and hepatosplenomegaly. 2

Secondary Causes to Exclude

Metabolic and Endocrine Conditions

• Diabetes mellitus (especially poorly controlled, insulinopenic diabetes) is the most common secondary cause, characterized by hypertriglyceridemia, low HDL, and small dense LDL particles due to hepatic VLDL overproduction and defective chylomicron clearance. 1, 2
• The prevalence of dyslipidemia is 2-3 times higher in diabetic patients compared to those with normal glucose tolerance. 2
• Hypothyroidism reduces lipoprotein lipase activity and impairs triglyceride clearance. 1
• Pregnancy (especially third trimester) can trigger severe hypertriglyceridemia in susceptible patients. 1

Obesity and Metabolic Syndrome

• Obesity and metabolic syndrome produce an atherogenic pattern with hypertriglyceridemia (elevated chylomicrons and VLDL), low HDL cholesterol, and small dense LDL particles. 2
• Insulin resistance drives hepatic VLDL overproduction with increased secretion of both triglycerides and apoB-100. 3
• Increased adipocyte lipolysis mobilizes free fatty acids that further drive hepatic VLDL secretion. 3

Medications and Lifestyle Factors

• Alcohol excess, especially with high saturated-fat diet, significantly elevates triglycerides. 1
• Medications including oral estrogens (not transdermal), beta-blockers (especially atenolol), thiazides, steroids, protease inhibitors, and atypical antipsychotics can cause severe hypertriglyceridemia. 1
• Bile acid resins should never be used with preexisting hypertriglyceridemia as they worsen triglyceride levels. 1

Key Distinguishing Features

What This Pattern Is NOT

• This is NOT familial combined hyperlipidemia (FCHL), which would show elevated apoB levels (>90th percentile) and typically presents with elevated LDL cholesterol in addition to triglycerides. 1, 4
• This is NOT dysbetalipoproteinemia (Type III), which shows approximately equal elevations of cholesterol and triglycerides (ratio ~1:1) with cholesterol levels 250-500 mg/dL and triglycerides 250-600 mg/dL. 1, 4
• This is NOT the typical diabetic dyslipidemia pattern alone, which shows modestly elevated triglycerides with low HDL but normal LDL levels. 1

Diagnostic Algorithm

• Measure fasting lipid panel: If triglycerides are 200-1000 mg/dL with low HDL and normal-to-low LDL, suspect familial hypertriglyceridemia. 1, 2
• Check apoB levels: Normal apoB (<90th percentile) confirms familial hypertriglyceridemia rather than FCHL. 1
• If triglycerides exceed 1000 mg/dL, immediately assess for pancreatitis risk and consider genetic lipoprotein lipase deficiency or severe secondary causes. 1, 2
• Screen for secondary causes: glucose/HbA1c (diabetes), TSH (hypothyroidism), alcohol history, medication review, and assess for metabolic syndrome components. 1, 2
• Obtain family history: Familial hypertriglyceridemia often requires an acquired "second hit" (obesity, diabetes, alcohol) for clinical expression. 1

Clinical Significance and Risk Assessment

Cardiovascular Risk

• Familial hypertriglyceridemia is usually not associated with coronary heart disease unless metabolic syndrome features are present or baseline triglyceride levels are high (≥200 mg/dL). 1
• Triglyceride-rich lipoproteins impair endothelial cell-dependent vasodilation, enhance monocyte recruitment to endothelium, and interfere with HDL's anti-inflammatory functions. 4
• The combination of elevated triglycerides and low HDL creates small, dense, highly atherogenic LDL particles despite normal measured LDL cholesterol. 4

Pancreatitis Risk

• When triglycerides exceed 1000 mg/dL, the immediate priority shifts to preventing acute pancreatitis, which supersedes cardiovascular risk management. 4
• Genetic causes (lipoprotein lipase deficiency, apolipoprotein CII deficiency) combined with acquired triggers (pregnancy, uncontrolled diabetes, alcohol) create the highest pancreatitis risk. 1

Critical Pitfall to Avoid

• Do not confuse this pattern with mixed hypercholesterolemia or FCHL—the key distinguishing feature is that LDL cholesterol is normal or LOW (not elevated), and apoB levels are normal (not elevated). 1, 4 The metabolic defect involves triglyceride-rich lipoprotein metabolism, not apoB-containing lipoprotein overproduction.