What is LDL (Low-Density Lipoprotein)?

Low-density lipoprotein (LDL) is the dominant form of atherogenic cholesterol that promotes atherosclerosis and cardiovascular disease. 1

Definition and Structure

LDL is a lipoprotein particle that transports cholesterol to peripheral tissues and can deposit in arterial walls, promoting plaque formation 2
LDL contains apolipoprotein B (apoB) as its main protein component, with one apoB molecule present on each LDL particle 1
LDL can be measured directly, but is usually calculated using the Friedewald formula:
- In mmol/L: LDL cholesterol = total cholesterol – HDL cholesterol – (0.45 × triglycerides) 1
- In mg/dL: LDL cholesterol = total cholesterol – HDL cholesterol – (0.2 × triglycerides) 1

LDL serves as the primary carrier of cholesterol in the bloodstream, delivering it to cells throughout the body 1
LDL is removed from circulation by LDL receptors on cell surfaces through receptor-mediated endocytosis 3
The liver contains the majority of physiologically important LDL receptors, where their number is regulated by the cholesterol content of hepatocytes 3

LDL is a proven causative factor for developing coronary artery disease (CAD), with a log-linear correlation between LDL-C levels and CAD risk 1, 4
LDL cholesterol is the primary target of cholesterol-lowering therapy in most guidelines, with the relationship between LDL reduction and cardiovascular risk following "the lower, the better" principle 2
For each 1.0 mmol/L (~40 mg/dL) reduction in LDL cholesterol, major vascular events and all-cause mortality are reduced by 22% and 10%, respectively 1

LDL particles are heterogeneous in size, density, and chemical composition 5
Small, dense LDL (sdLDL) particles possess stronger atherogenic ability compared to larger LDL subfractions 5, 6
The presence of small, dense LDL is part of an "atherogenic lipoprotein phenotype" that includes elevated triglycerides and low HDL cholesterol 6
When plasma triglycerides exceed approximately 133 mg/dL (1.5 mmol/L), this favors the formation of small, dense LDL from larger, less dense species 6

The American College of Cardiology recommends the following LDL cholesterol categories: 2
- Very high: ≥175 mg/dL
- High: 150-174 mg/dL
- Borderline high: 125-149 mg/dL
- Borderline low: 100-124 mg/dL
- Low: 75-99 mg/dL
- Very low: 50-74 mg/dL
- Optimal: <100 mg/dL
In high-risk patients, an LDL cholesterol goal of <1.8 mmol/L (less than 70 mg/dL) or a ≥50% LDL cholesterol reduction is recommended 1
For patients at moderate risk, an LDL cholesterol goal of <3.0 mmol/L (less than 115 mg/dL) should be considered 1

Non-HDL cholesterol (total cholesterol minus HDL cholesterol) may be a better predictor of cardiovascular risk than LDL alone, especially in patients with elevated triglycerides 1, 2
Apolipoprotein B (apoB) may more directly measure circulating atherogenic lipoproteins than LDL cholesterol 1
The apoB:apoA1 ratio is one of the strongest risk markers for cardiovascular disease, though it is not yet established as a treatment goal 1

Statins are the first-line therapy for LDL reduction, lowering LDL by 35-55% depending on type and dose 2, 7
Other LDL-lowering options include ezetimibe, bile acid sequestrants, and PCSK9 inhibitors 2
Atorvastatin and other statins are indicated to reduce LDL-C in adults with primary hyperlipidemia and in patients with heterozygous familial hypercholesterolemia 7