Sandesara 2019: Atherogenic Lipoprotein Subfractions

Background

Dr. Pratik B. Sandesara and colleagues published this review in the Journal of the American Heart Association (PMID: 30312399), examining atherogenic lipoprotein subfractions including remnant cholesterol.

Study Design

Review synthesizing evidence on lipoprotein subfractions beyond standard LDL-C, with focus on remnant cholesterol and its cardiovascular implications.

Key Findings

Remnant cholesterol definition:

• •Calculated: Total-C − LDL-C − HDL-C
• •Represents cholesterol in VLDL, IDL, and chylomicron remnants

Evidence for remnant cholesterol:

Evidence Type	Key Finding
Observational	Independent CVD predictor
Mendelian randomization	Causal relationship established
Mechanistic	Direct arterial wall penetration

Comparison with LDL-C:

• •Remnants don't require oxidation for macrophage uptake
• •More pro-inflammatory than native LDL
• •Often elevated when triglycerides high
• •Not captured by LDL-C measurement

Mechanistic Insights

Remnant particles are atherogenic because:

1. •Small enough to enter arterial intima
2. •Directly taken up by macrophages (no oxidation needed)
3. •Cholesterol-rich (higher cholesterol per particle than LDL)
4. •Pro-inflammatory (activate endothelium)

Clinical Implications

Elevated remnant cholesterol (>30 mg/dL) indicates:

• •Triglyceride-rich lipoprotein excess
• •Potential underestimation of CVD risk by LDL alone
• •Need for triglyceride-lowering strategies

Metabolic Health Perspective

Remnant cholesterol responds dramatically to carbohydrate restriction (as triglycerides fall). It provides additional insight beyond LDL-C and represents an emerging target for metabolic cardiovascular risk assessment.