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Test ID: LDLPL    
LDL Particle Concentration NMR with Lipids, Plasma

Useful For Suggests clinical disorders or settings where the test may be helpful

Assessment and management of a patient's risk for cardiovascular disease and events 

                                                        

Identifying residual risk that may be present in some patients, despite having traditional lipid values at target concentrations, and guiding therapy in such patients

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The key role of low-density lipoprotein (LDL) particles in the pathogenesis of cardiovascular disease is well recognized, as is the benefit of lowering LDL in high-risk patients. What remains controversial is the best measure of LDL to identify all individuals at risk, and those who will benefit from therapy. Many studies have shown that individuals with predominantly small LDL particles are at greater risk for adverse cardiovascular events. However, the phenotype of small LDL particle size co-segregates with a cluster of metabolic factors including high-density lipoprotein (HDL) cholesterol and triglycerides, and in multivariate analyses adjusting for these measures, LDL size has generally not been found to be independently associated with increased risk of adverse events.

 

Recent studies have shown that measures of small- and large-sized LDL particle concentrations, assessed by either nuclear magnetic resonance (NMR) or apolipoprotein B, a major protein component of LDL, are more strongly associated with cardiovascular disease than is LDL size phenotype or LDL cholesterol concentration and have consistently been found to be independently associated with coronary heart disease (CHD) risk. The numbers of atherogenic LDL particles are frequently elevated, even though LDL cholesterol concentration is not. This appears to be particularly true for those patients with diabetes and insulin resistance. In the Veterans Affairs High Density Lipoprotein Intervention Trial (VA-HIT), which included a relatively large proportion of subjects with diabetes (30%) and insulin resistance (30%), both traditional risk factors and NMR analyses were assessed in patients treated with the lipid-modifying agent gemfibrozil or placebo. LDL cholesterol was not influenced by treatment with gemfibrozil, but HDL cholesterol concentration was increased by 6% and was associated with a 22% reduction in CHD events. While LDL cholesterol was not changed, LDL particle concentration was decreased by 5%, small LDL particle concentration was decreased by 20%, HDL particle number was increased by 10%, and small HDL particle number was increased by 21%. Interestingly, neither baseline nor on-trial concentrations of HDL cholesterol, LDL cholesterol, or triglycerides were significant predictors of CHD events. Among NMR lipoproteins measured, both baseline and on-trial concentrations of LDL and HDL particle numbers were independent predictors of new CHD events with on-trial P values of 0.0003 and <0.0001, respectively. Neither LDL nor HDL particle size was related to CHD events.

 

In the PROVE IT TIMI 22 trial, which compared treatment with high-dose atorvastatin to standard-dose pravastatin, high-dose atorvastatin was found to confer a 16% reduction in the hazard ratio in comparison to standard-dose pravastatin. In the high-dose group, the median LDL cholesterol concentration achieved was 62 mg/dL, well below the recommended target for LDL lowering. Although this did result in decreased risk for events, there was still residual risk in this group, with 22% of enrolled patients experiencing a poor outcome (death or major cardiovascular event) within 2 years of enrollment. Determination of lipoprotein-particle concentration in such patients represents a potential strategy for identifying this residual risk, and may serve as a guide to therapy in patients with residual risk.   

 

This test provides traditional lipid panel results (total cholesterol, triglycerides, HDL, and calculated LDL cholesterol), as well as values for total LDL particle concentrations.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

The National Cholesterol Education Program (NCEP) has set the following guidelines for lipids (total cholesterol; triglycerides; HDL; and LDL cholesterol) in adults ages 18 and up:

 

TOTAL CHOLESTEROL

Desirable: <200 mg/dL

Borderline high: 200-239 mg/dL

High: > or =240 mg/dL

 

TRIGLYCERIDES

Normal: <150 mg/dL

Borderline high: 150-199 mg/dL

High: 200-499 mg/dL

Very high: > or =500 mg/dL

 

HDL CHOLESTEROL

Low: <40 mg/dL

Normal: 40-59 mg/dL

High: > or =60 mg/dL

 

LDL CHOLESTEROL

Optimal: <100 mg/dL

Near optimal: 100-129 mg/dL

Borderline high: 130-159 mg/dL

High: 160-189 mg/dL

Very high: > or =190 mg/dL

 

NON-HDL CHOLESTEROL

Desirable: <130 mg/dL

Borderline high: 130-159 mg/dL

High: 160-189 mg/dL

Very high: > or =190 mg/dL

 

The National Cholesterol Education Program (NCEP) and National Health and Nutrition Examination Survey (NHANES) have set the following guidelines for lipids (total cholesterol, triglycerides, HDL, and LDL cholesterol) in children ages 2-17:

 

TOTAL CHOLESTEROL

Desirable: <170 mg/dL

Borderline high: 170 -199 mg/dL

High: > or =200 mg/dL

 

TRIGLYCERIDES

Normal: <90 mg/dL

Borderline high: 90-129 mg/dL

High: > or =130 mg/dL

 

HDL CHOLESTEROL

Low: <40 mg/dL

Normal: 40-59 mg/dL

Desirable: > or =60 mg/dL

 

LDL CHOLESTEROL

Desirable: <110 mg/dL

Borderline high: 110-129 mg/dL

High: > or =130 mg/dL

 

NON-HDL CHOLESTEROL

Desirable: <130 mg/dL

Borderline high: 130-159 mg/dL

High: 160-189 mg/dL

Very high: > or =190 mg/dL

 

NMR LIPOPROTEIN PARTICLES : TOTAL LDL PARTICLE CONCENTRATION

Pediatrics (< or =15 years): not established

Adults (> or =16 years):

<1,000 nmol/L (Optimal)

1,000-1,299 nmol/L (Near or above optimal)

1,300-1,599 nmol/L (Borderline high)

1,600-2,000 nmol/L (High)

>2,000 nmol/L (Very high)

Interpretation Provides information to assist in interpretation of the test results

Traditional risk factors should be interpreted and optimally treated according to guidelines from by the National Cholesterol Education Program Adult Treatment Panel (ATPIII): for treatment guidelines see Reference Values.(1)

                                                                                 

Elevated low-density lipoprotein (LDL) particle concentrations are associated with increased risk of coronary heart disease, and may be reflective of residual risk in patients who meet target LDL cholesterol concentrations.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Fasting is required. Failure to follow specimen collection requirements may adversely affect the ability to properly interpret results.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001 May 16;285:2486-2497

2. Rosenson RS, Otvos JD, Freedman DS: Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) trial. Am J Cardiol 2002 Jul 15;90(2):89-94

3. Pischon T, Girman CJ, Sacks FM, et al: Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation 2005 Nov 29;112 (22):3375-3383

4. Otvos JD, Collins D, Freedman DS, et al: Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation 2006 Mar 28;113(12):1556-1563

5. Cannon CP, Braunwald E, McCabe CH, et al: Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004 Apr 8;350(15):1495-504