Multi-Ethnic Study of Atherosclerosis Weight of Evidence Who Needs the Test? What is Discordance?

The Multi-Ethnic Study of Atherosclerosis (MESA)¹

MESA is an NHLBI multi-center study of ethnically-diverse men and women free of cardiovascular disease at entry.

MESA joins Framingham Offspring² and other outcome studies in validating the clinical utility of LDL-P for guiding therapeutic decision-making and refining LDL management.

CLINICAL OUTCOMES TRACK WITH LDL PARTICLE NUMBER (LDL-P)

In this community-based cohort of MESA that followed 5,598 individuals, the cumulative incidence of CVD events tracked with elevated levels of LDL-P regardless of levels of LDL-C.

According to the 2008 ADA/ACC Consensus Statement

"Measurement of LDL cholesterol (LDL-C) may not accurately reflect the true
burden of atherogenic LDL particles."³

1. Otvos JD, Mora S., Shalaurova I, et al. Clinical Implications of Discordance Between LDL Cholesterol and LDL Particle Number. J.Clin Lipidology, 2011;5(2):105-113.
2. Crowell WC, Otvos JD, Keyes MJ, et. al. LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study – Implications for LDL management. J.Clin Lipidology, 2007;1(6):583-592.
3. Brunzell JD, Davidson M, Furberg, CD, et al. LipoProtein Management in Patients with Cardiometabolic Risk. J. Am Coll. Cardiol. 2008;51;1512-24.

Weight of Evidence

To date over 210 papers demonstrating the clinical utility of LDL-P have been published in peer-reviewed journals including:

Journal of the American Medical Association
New England Journal of Medicine

American Journal of Cardiology
Circulation

The NMR LipoProfile test — The Particle Test — has been used to study over 47,000 subjects in nine cardiovascular outcomes studies using LDL-P and other lipoprotein particle concentrations as indicators of outcomes.

CVD Outcomes Studies	Endpoints	Subjects	Subject Type
Clinical Implications of Discordance Between Low-density Lipoprotein Cholesterol and Particle Number (MESA) Otvos et al. J Clin Lipidology 2011 click here to download PDF of abstract	Incident MI, Stroke, CVD Death, Angina	n=5,598	Healthy Men and Women
Women's Health Initiative Hormone Trials Hsia et al. Arterioscler Thromb Vasc Biol 2008 click here to download PDF of abstract	MI, Coronary Death	n=708	Healthy Women
Framingham Offspring Study Cromwell et al. J Clin Lipidology 2007 click here to download PDF of abstract	Incident MI, Stroke, CVD Death, Angina	n=3,066	Healthy Men and Women
Multi-Ethnic Study of Atherosclerosis (MESA) Mora et al. Atherosclerosis 2007 click here to download PDF of abstract	Carotid Intima-Media Thickness (IMT)	n=5,538	Healthy Men and Women
European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk El Harchaoui et al. J Am Coll Cardiol 2007 click here to download PDF of abstract	Fatal or Non-Fatal CAD	n=2,888	Healthy Men and Women
Veterans Affairs HDL Intervention Trial (VA-HIT) Otvos et al. Circulation 2006 click here to download PDF of abstract	Nonfatal MI or CHD Death	n=1,061	Men with Known CHD & Low HDL-C
Pittsburgh Epidemiology of Diabetes Complications Study Soedamah-Muthu et al. Diabetologia 2003	MI, CHD Death, Coronary Revascularization	n=118	Type I Diabetic Men and Women
Cardiovascular Health Study (CHS) Kuller et al. Arterioscler Thromb Vasc Biol 2002	Incident MI or Angina	n=1,175	Elderly
Pravastatin Limitation of Atherosclerosis in Coronary Arteries (PLAC-1) Rosenson et al. Am J Cardiol 2002	Angiographic Minimum Lumen Diameter	n=241	Patients with Known CHD

Click HERE to download a copy of the chart above.

Who Needs the Test?

Ideal candidates for LDL-P management are high cardiometabolic risk or diabetic patients whose LDL-C may be considered normal. Many patients with these conditions have relatively normal levels of LDL-C but increased LDL-P.

Even with adequate cholesterol lowering, they may continue to have significant residual CVD risk.1

If your patient has any of these factors that contribute to cardiometabolic risk, the NMR LipoProfile test — The Particle Test — may be right for them:

Diabetes
Cardiometabolic risk
Metabolic syndrome
Previous heart attack
Family history of heart disease
High blood pressure
Overweight/obesity
Low HDL (dyslipidemia)
High triglycerides

1. Brunzell JD, Davidson M, Furberg, CD, et al. LipoProtein Management in Patients with Cardiometabolic Risk. J. Am Coll. Cardiol. 2008;51;1512-24

What is Discordance?

'Discordance' occurs when LDL cholesterol (LDL-C) and LDL particle number (LDL-P) don't agree. When discordance is present, risk of cardiovascular disease tracks with LDL-P, and incidence of cardiovascular events increases with elevated LDL-P. (See MESA, Health Care Professional Resource Center.)

Discordant results between LDL-C and LDL-P are common. Many patients with normal LDL-C have elevated LDL-P indicating they have residual risk.

LDL Particles Cause Plaque¹

Plaque Progression: More LDL Particles = More Plaque

The higher the number of LDL particles, the greater the likelihood for them to enter the arterial wall and deposit their contents forming atherosclerotic plaque. Measurement of LDL-C on traditional lipid panels does not reflect LDL particle number.

Click HERE to download a PDF of LDL Particles Cause Plaque.