Classification: Hypertriglyceridemia, Not Mixed Hyperlipidemia
Your patient has hypertriglyceridemia—specifically, a pattern consistent with familial hypertriglyceridemia or metabolic syndrome-associated dyslipidemia—not mixed hyperlipidemia. The distinguishing feature is that mixed hyperlipidemia requires both elevated LDL-cholesterol (≥130 mg/dL) and elevated triglycerides (≥150 mg/dL), whereas your patient has low HDL and elevated triglycerides without mention of elevated LDL 1, 2.
Key Distinguishing Features
Why This Is Hypertriglyceridemia
Low HDL with elevated triglycerides represents the classic "atherogenic dyslipidemia" pattern, characterized by increased VLDL remnants, small dense LDL particles, and reduced HDL-C—but critically, this occurs with normal or low LDL-cholesterol levels 3.
The low HDL results directly from the elevated triglycerides: excess triglycerides are transferred from VLDL to HDL particles via cholesteryl ester transfer protein (CETP), depleting HDL of cholesterol and accelerating its catabolism 3, 4.
This pattern is most commonly seen in familial hypertriglyceridemia (affecting 5-10% of the population), metabolic syndrome, or type 2 diabetes, where the primary metabolic defect involves VLDL overproduction and impaired triglyceride clearance—not LDL overproduction 1, 5.
Why This Is NOT Mixed Hyperlipidemia
Mixed hyperlipidemia (also called combined hyperlipidemia) requires simultaneous elevation of both LDL-cholesterol and triglycerides, typically with LDL-C ≥130 mg/dL and triglycerides ≥150 mg/dL 2.
The hallmark of mixed hyperlipidemia is elevated apolipoprotein B (apoB > 90th percentile), reflecting overproduction of multiple apoB-containing lipoproteins (VLDL, IDL, and LDL) 1, 2.
Your patient's pattern—with normal or low LDL—indicates normal apoB levels, which excludes familial combined hyperlipidemia and confirms the defect is isolated to triglyceride-rich lipoprotein metabolism 1.
Diagnostic Algorithm to Confirm
Obtain These Specific Values
Measure LDL-cholesterol directly: If LDL-C is <130 mg/dL, this confirms hypertriglyceridemia rather than mixed hyperlipidemia 1, 2.
Check apolipoprotein B if available: Normal apoB (<90th percentile, typically <100 mg/dL) definitively rules out familial combined hyperlipidemia and supports isolated hypertriglyceridemia 1.
Calculate non-HDL cholesterol (total cholesterol minus HDL): This reflects the total burden of atherogenic particles; in isolated hypertriglyceridemia, non-HDL may be modestly elevated due to VLDL but not as high as in mixed hyperlipidemia 2.
Screen for Secondary Causes
Check fasting glucose and HbA1c: Diabetes mellitus—especially poorly controlled or insulin-deficient states—is the most common secondary cause of this lipid pattern, producing hypertriglyceridemia and low HDL through hepatic VLDL overproduction and impaired chylomicron clearance 3, 1, 5.
Measure TSH: Hypothyroidism impairs lipoprotein lipase activity, reducing triglyceride clearance 1.
Review medications: Oral estrogens, beta-blockers (especially atenolol), thiazide diuretics, systemic corticosteroids, protease inhibitors, and atypical antipsychotics can all precipitate severe hypertriglyceridemia 1.
Assess alcohol intake and dietary fat: Excessive alcohol and high saturated-fat diets markedly raise triglycerides 1, 6.
Evaluate for metabolic syndrome components: Abdominal obesity, insulin resistance, hypertension, and impaired fasting glucose frequently coexist with this lipid pattern 3, 6.
Clinical Implications and Risk Stratification
Cardiovascular Risk
Elevated triglycerides are causally associated with atherosclerotic cardiovascular disease independent of HDL levels, as demonstrated by Mendelian randomization studies showing that genetically elevated triglycerides increase ischemic heart disease risk even after adjusting for LDL and HDL 3.
Low HDL cholesterol per se is not causally related to cardiovascular disease when accounting for triglycerides and LDL; it serves as a marker of increased risk rather than a therapeutic target 3, 7.
The combination of elevated triglycerides and low HDL creates small, dense, highly atherogenic LDL particles, even when LDL-cholesterol levels appear normal 3, 5.
Pancreatitis Risk
If triglycerides exceed 1000 mg/dL, preventing acute pancreatitis becomes the immediate priority, superseding cardiovascular risk management 1, 2, 6.
Genetic lipoprotein lipase deficiency combined with secondary triggers (pregnancy, uncontrolled diabetes, alcohol) confers the highest pancreatitis risk 1.
Common Pitfalls to Avoid
Do not misclassify this as mixed hyperlipidemia based solely on "multiple lipid abnormalities": The term "mixed" specifically refers to combined elevation of LDL-cholesterol and triglycerides, not just any combination of lipid derangements 1, 2.
Do not assume all dyslipidemia with low HDL requires aggressive HDL-raising therapy: Low HDL in the setting of hypertriglyceridemia is a consequence of the elevated triglycerides and will improve when triglycerides are lowered 3, 4.
Avoid bile-acid resins in patients with pre-existing hypertriglyceridemia, as they exacerbate triglyceride elevation 1.
Do not overlook secondary causes: Uncontrolled diabetes is the most frequent precipitant and must be addressed before attributing the lipid pattern to primary genetic hypertriglyceridemia 3, 1, 5.