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Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease

Ron C Hoogeveen, John W Gaubatz, Wensheng Sun, Rhiannon C Dodge, Jacy R Crosby, Jennifer Jiang, David Couper, Salim S Virani, Sekar Kathiresan, Eric Boerwinkle, Christie M Ballantyne

Arteriosclerosis, Thrombosis, and Vascular Biology 2014

Small, dense LDL exposes hidden heart risk: it predicts events even when LDL looks “normal.”

Study Details

Journal Arteriosclerosis, Thrombosis, and Vascular Biology
Year 2014
URL: www.ahajournals.org
2 min read

Table of Contents

Higher levels of small, dense LDL cholesterol predict more heart disease, even when LDL is “normal”.

The Hidden Risk Inside “Normal” Cholesterol

Main finding

People with higher levels of small, dense LDL cholesterol (sdLDL-C) had more heart disease, even when their standard LDL cholesterol looked “normal” (<100 mg/dL).

  • sdLDL-C refers to the smaller, denser LDL particles that are more likely to cause artery damage. Standard LDL-C is the total cholesterol carried by all LDL particles.

What the study did

Researchers measured sdLDL-C in 11,419 adults from the ARIC study and tracked heart events for about 11 years. They compared people in the lowest sdLDL-C group to the highest.

Key results

  • Those in the highest sdLDL-C group had a 51% higher risk of heart disease than the lowest group after accounting for age, sex, race, smoking, blood pressure, weight, HDL (“good” cholesterol), triglycerides, diabetes, medications, and inflammation markers.
  • Even with LDL-C <100 mg/dL, higher sdLDL-C still predicted more heart disease (61% higher risk in the top sdLDL-C group).
  • Large, buoyant LDL (lbLDL-C) did not show a clear link with future heart disease.
  • Genetics: variants in 8 gene regions were tied to sdLDL-C, including a novel link to PCSK7. A specific PCSK7 variant raised sdLDL-C and triglycerides and was associated with heart disease in a large genetic dataset.

What this challenges

  • “Normal” LDL-C can miss risk: the type of LDL particle matters.
  • sdLDL-C is more closely tied to risk than large LDL particles, and adds risk information beyond standard LDL-C.

Practical relevance (especially for people with diabetes)

  • sdLDL-C tended to be higher in diabetes and in people with metabolic syndrome, and tracked with an “atherogenic” profile: higher triglycerides, lower HDL-C.
  • For ordinary people: if you have diabetes or features of metabolic syndrome, sdLDL-C may reveal hidden risk even when your LDL-C looks fine.

What you can do (based on this paper’s implications)

  • Consider asking about sdLDL-C testing using the homogeneous sdLDL-C assay described in the study; it’s compatible with routine lab analyzers.
  • Pay attention to the overall lipid pattern: high triglycerides + low HDL-C often coexist with higher sdLDL-C.

Important caveats

  • When adjusted for other tightly related lipid measures (LDL-C, apoB, total cholesterol), sdLDL-C wasn’t independently predictive—likely because these measures overlap strongly.
  • The study did not include LDL particle number; the exact role of “how many particles” versus “particle type” remains debated.

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