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The role of particle size and density in cardiovascular risk assessment

Evolving guidelines continue to focus on traditional factors to manage cardiovascular risk. While standard lipid screening plays an important role in risk assessment, it may not always be predictive of adverse events. That’s because residual cardiovascular risk can still be significant despite management of traditional risk factors.1

Cardiovascular risk assessment has evolved beyond lipid values to include inflammation, lipoprotein subfractions, and apolipoproteins. Studies show that LDL and HDL subclasses are predictive of short- and long-term cardiovascular disease (CVD) risk, atherosclerotic progression, and multiple intervention events.

The Québec Cardiovascular Study (1997) was the first to suggest that the presence of small, dense LDL particles may be associated with an increased risk of developing CVD.2 A heart attack can occur when the LDL particle number is high and the LDL level is low—indicating CVD risk that standard lipid panel testing may not reveal.1

The Québec Cardiovascular Study (1997) was the first to suggest that the presence of small, dense LDL particles may be associated with an increased risk of developing CVD.2 A heart attack can occur when the LDL particle number is high and the LDL level is low—indicating CVD risk that standard lipid panel testing may not reveal.1

"Recent data suggests that even after statin therapy, residual risk still exists in many patients.²"

Going beyond standard lipid panels to assess lipoprotein and apolipoprotein risk factors may provide deeper insights into the residual risk of your patients.

Your patients may benefit from advanced lipid testing

Patients who may benefit from advanced testing include those with:

  • Established CVD
  • Diabetes
  • Hypertension
  • Metabolic syndrome
  • Elevated LDL-C >=190 mg/dL
  • >=5% estimated ASCVD risk
  • Other traditional risk factors, including

> Age (men >45 years; post-menopausal women)

> Family history of premature onset of CVD

> Unhealthy diet, excessive alcohol intake, smoking, and/or stress

> Obesity

> Low HDL-C


Do more to identify residual risk

Advanced biomarkers have been shown to help identify residual risk and have been adopted by several guidelines and societies.3,4 With deeper insights, you can take further action to help reduce your patients’ risk for adverse cardiovascular events.

Lipoprotein risk factors

Risk factor Clinical utility
LDL Particle Number The Québec Cardiovascular Study was the first to demonstrate that heart attack can occur when LDL particle number is high and low-density lipoprotein level is low.2 Greater numbers of cholesterol-containing particles in the blood means more cholesterol deposition in plaque and therefore an increased risk for heart attack
HDL subclasses A low level of large HDL particles may reduce the efficacy of the reverse cholesterol transport process. The large HDL subclass was identified in the Malmö Diet and Cancer Study to be inversely correlated with coronary heart disease risk
LDL subclasses Small LDL subclass particles cause plaque buildup to progress much faster because they enter the artery wall more easily than large LDL particles. A predominance of smaller LDL particles, referred to as Pattern B lipid phenotype, represents an atherogenic lipid profile that is associated with CVD
ApoB ApoB is the primary apolipoprotein attached to all atherogenic particles. It is involved in the metabolism and transport of lipids. A high ApoB number indicates increased risk for heart disease
Lp(a) Lipoprotein(a) is an inherited protein that is attached to LDL. High levels of lipoprotein(a) increase risk of coagulation and contribute to atherosclerosis

This information is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.

Understand a powerful cardiac risk factor: familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a common inherited disorder characterized by very high LDL-C and a greater risk for premature coronary heart disease (CHD). Despite its common occurrence, most FH goes undiagnosed.5

Patients suitable for FH testing include:

  • Adults with untreated LDL-C levels >=190 mg/dL (>=160 mg/dL with treatment)
  • Children with untreated LDL-C levels >=160 mg/dL
  • Individuals with a personal or family history of premature CHD or other CVD
  • Individuals with xanthomas or corneal arcus

Cardio IQ® genetic testing for FH from Quest examines LDL receptor (LDLR), apolipoprotein B (ApoB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) to provide actionable information that may lead to earlier treatment and a lower lifetime risk of CVD.

Learn more about cardiogenetic testing.

Cardio IQ® advanced lipid testing from Quest Diagnostics

Advanced cardiovascular testing provides actionable information to individualize treatment options:

  • Initiate/intensify statin therapy
  • Identify opportunities for adjunct therapy
  • Set diet, exercise, and lifestyle targets

Review the complete Cardio IQ® advanced lipid test list and descriptions.

Greater accuracy: LDL-C assessment

The commonly used value for LDL-C is not derived from direct measurement, but from an estimate. Quest Diagnostics provides the new Martin-Hopkins Calculation, offering increased accuracy and convenience.

Learn more.

Contact Quest Genomics Client Services to speak with a genetic counselor at 1.866.436.3463

Contact us


  1. Lamarche B, Tchernof A, Moorjani S, et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study. Circulation. 1997;95(1):69-75.
  2. Reith C and Armitage J. Management of residual risk after statin therapy. Atherosclerosis. 2016;245:161-170. Third report of the National Cholesterol Program (NCEP) Expert Panel. 2002; September; Section IV-8; tables IV2-2, IV2-3:108-110.
  3. Davidson MH, Corson MA, Alberts MJ, et al. Consensus panel recommendation for incorporating lipoprotein-associated phospholipase A2 testing into cardiovascular disease risk assessment guidelines. Am J Cardiol. 2008;101(12A):51F-57F.
  4. Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients. Clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clinical Lipidology. 2011;5,S1-S8.

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