What is the lipid diagnosis for a patient with elevated LDL, high triglycerides, and other lipid profile abnormalities?

Lipid Diagnosis: Mixed Dyslipidemia (Combined Hyperlipidemia)

This patient has mixed dyslipidemia, characterized by borderline-elevated LDL cholesterol (107 mg/dL), elevated triglycerides (250 mg/dL), and critically low HDL cholesterol (47 mg/dL), representing an atherogenic lipid profile that significantly increases cardiovascular risk. 1

Diagnostic Classification

Primary Lipid Abnormalities Identified

• Elevated triglycerides (250 mg/dL): This exceeds the threshold of ≥150 mg/dL that defines hypertriglyceridemia and is associated with the atherogenic lipoprotein phenotype 1, 2

• Low HDL cholesterol (47 mg/dL): While technically above the strict cutoff of <40 mg/dL for men, this falls in the borderline-low range (<50 mg/dL for women if applicable) and contributes to cardiovascular risk 1, 3

• Borderline-elevated LDL cholesterol (107 mg/dL): Although below the 130 mg/dL treatment threshold, this level combined with elevated triglycerides suggests the presence of small, dense LDL particles that are more atherogenic 1, 4

• Calculated non-HDL cholesterol: Total cholesterol (180 mg/dL) minus HDL (47 mg/dL) = 133 mg/dL non-HDL cholesterol, which represents all atherogenic lipoproteins 1, 5

Pattern Recognition

This constellation represents familial combined hyperlipidemia or metabolic dyslipidemia, characterized by: 1

• Overproduction of VLDL particles leading to elevated triglycerides 1
• Increased small, dense LDL particles despite only modestly elevated LDL-C 1, 4
• Reduced HDL cholesterol due to enhanced cholesteryl ester transfer protein-mediated exchange 1
• Moderately increased risk of premature cardiovascular disease 1

Clinical Significance and Risk Assessment

Atherogenic Profile Components

• The combination of elevated triglycerides and low HDL represents a "hypertriglyceridemic waist" pattern when accompanied by central obesity, strongly associated with increased myocardial infarction and stroke risk 1, 2

• Triglycerides >150 mg/dL indicate elevated triglyceride-rich lipoproteins and remnant particles, which have established causal associations with atherosclerotic cardiovascular disease through mechanistic, genetic, and epidemiological evidence 1, 2, 6

• The low HDL-HDL ratio is unfavorable, suggesting increased cardiovascular risk beyond what LDL alone would predict 5, 7

Underlying Mechanisms to Evaluate

Assess for insulin resistance and metabolic syndrome, as this lipid pattern is characteristic of: 1

• Hyperinsulinemia enhancing hepatic VLDL synthesis 1
• Resistance to insulin action on lipoprotein lipase in peripheral tissues 1
• Increased apolipoprotein A1/HDL degradation exceeding synthesis 1
• Overweight/obesity and type 2 diabetes as common contributors 1

Evaluate for secondary causes of dyslipidemia: 1, 2

• Diabetes mellitus (check HbA1c and fasting glucose) 1
• Chronic kidney disease (check creatinine and urinalysis for proteinuria) 1
• Hypothyroidism (check TSH) 1
• Excessive alcohol intake 1
• Medications that worsen lipid profiles 1

Differential Considerations

• Familial combined hyperlipidemia: Autosomal dominant inheritance with multiple phenotypes in family members, elevated apolipoprotein B, overproduction of VLDL particles 1

• Metabolic syndrome-associated dyslipidemia: Insulin resistance as the central pathophysiological mechanism, often with concurrent hypertension, central obesity, and impaired glucose tolerance 1

• Type 2 diabetes-associated dyslipidemia: The most common pattern in T2DM is elevated triglycerides, reduced HDL-C, and presence of smaller cholesterol ester-depleted LDL particles 1

Important Caveats

• Non-HDL cholesterol (133 mg/dL) should be used as a secondary treatment target in patients with elevated triglycerides, as it captures all atherogenic lipoproteins including VLDL remnants not reflected in LDL-C alone 1, 5

• The apparently "normal" total cholesterol (180 mg/dL) is misleading in this context, as it masks the atherogenic dyslipidemia pattern of elevated triglycerides and low HDL 1, 7

• Small, dense LDL particles are likely present despite only borderline-elevated LDL-C, as triglycerides >150 mg/dL are associated with this atherogenic LDL phenotype 1, 4, 7