What is mixed dyslipidemia?

What is Mixed Dyslipidemia?

Mixed dyslipidemia is a lipid disorder characterized by simultaneous elevations in total cholesterol, LDL cholesterol, and triglycerides, typically accompanied by decreased HDL cholesterol levels, creating a highly atherogenic lipid profile that substantially increases cardiovascular disease risk. 1

Defining Characteristics

The lipid profile in mixed dyslipidemia demonstrates:

• LDL-C ≥130 mg/dL 1
• Triglycerides ≥150 mg/dL 1
• Low HDL cholesterol (often <40 mg/dL in men, <50 mg/dL in women) 2, 3
• Elevated total cholesterol 1

This pattern represents any combination of elevated total cholesterol or LDL-cholesterol, decreased HDL-cholesterol, and elevated triglycerides, with abnormal composition of lipoproteins. 4

Clinical Patterns and Subtypes

Mixed dyslipidemia manifests in several forms:

Primary (Genetic) Forms

• Familial Combined Hyperlipidemia (FCHL) is the most common primary dyslipidemia with a population prevalence of 5-10%, characterized by multiple lipoprotein abnormalities due to hepatic overproduction of apoB-containing lipoproteins (VLDL, IDL, LDL). 1
• Type III Dysbetalipoproteinemia presents with elevations of both cholesterol and triglycerides with a cholesterol-to-triglyceride ratio of approximately 1:1. 1

Secondary Forms

• Diabetes mellitus (both Type 1 and Type 2) is characterized by hypertriglyceridemia, low HDL-cholesterol, and small dense LDL particles, resulting from hepatic VLDL overproduction and defective chylomicron clearance. 4
• Obesity and metabolic syndrome are associated with an atherogenic pattern: hypertriglyceridemia (elevated chylomicrons and VLDL), low HDL-cholesterol, small dense LDL, and oxidized LDL. 4
• The prevalence of dyslipidemia is 2-3 times higher in diabetic patients compared to those with normal glucose tolerance. 4

Multifactorial Forms

• Multifactorial dyslipidemia involves both polygenic predisposition and environmental factors, defined by LDL-cholesterol ≥130 mg/dL or total cholesterol ≥200 mg/dL not attributable to familial hypercholesterolemia. 4
• This condition is strongly associated with obesity, causing slight LDL-cholesterol elevation but more pronounced triglyceride elevation and HDL-cholesterol reduction. 4

Pathophysiology and Atherogenic Mechanisms

Mixed dyslipidemia significantly increases cardiovascular disease risk through multiple mechanisms:

• Triglyceride-rich lipoproteins (TRLs) impair endothelial cell-dependent vasodilation, enhance recruitment of monocytes to endothelium, and interfere with HDL's anti-inflammatory functions. 1
• The combination of elevated triglycerides and low HDL creates small, dense, highly atherogenic LDL particles. 1
• The atherogenic lipid triad is characterized by increased VLDL remnants, increased small dense LDL particles, and reduced HDL-C. 4

Diagnostic Approach

Diagnosis requires:

• Complete lipid profile showing elevated LDL-C, total cholesterol, and triglycerides. 1
• Non-HDL cholesterol (total cholesterol minus HDL cholesterol) is a valuable marker in mixed dyslipidemia. 1
• Apolipoprotein B levels can be useful as they reflect the total number of atherogenic particles. 1

Clinical Significance

Cardiovascular Risk

• Mixed dyslipidemia creates an atherogenic pattern that increases cardiovascular risk beyond isolated LDL elevation. 1
• In patients with diabetes and mixed dyslipidemia, 50% of mortality is from coronary artery disease. 1

Critical Threshold

• When triglycerides are severely elevated (>1000 mg/dL), the immediate priority shifts to preventing pancreatitis, superseding cardiovascular risk management. 1

Common Clinical Contexts

Mixed dyslipidemia is most frequently observed in:

• Metabolic syndrome patients, who often present with normal total cholesterol but abnormal composition of lipoproteins. 4
• Type 2 diabetes mellitus patients, where the atherogenic lipoprotein phenotype is typical. 3
• Patients with obesity, where environmental factors combine with genetic predisposition. 4