Biomarkers for the Detection and Monitoring of Coronary Artery Disease

Description:

The inventors have developed a methodology that has been robustly validated (~800 patients) to accurately and reliably measure Ox-LDL, AGE-LDL and other modified LDLs circulating in bound/immune-complex (IC) form. The method involves isolation of IC from blood samples and fractionation of the isolated IC in order to separate modified forms of LDL that can then be quantitated with specific antibodies to Ox-LDL, MDA-LDL and AGE-LDL. The concentrations and relative distribution of modified LDL contained in the IC have been identified as risk factors for the progression of coronary heart disease  (CHD) and able to predict patients at high risk to have a myocardial infarction and other acute cardiovascular (CVD) events. Some modified LDL-IC are strong predictors of development and progression of CHD and some are strong predictors of acute CVD events. Studies are now being programmed to perform these tests in patients without diabetes and in patients with pre-diabetes and metabolic syndrome using samples from the REGARDS study to expand the findings in diabetes to a non-diabetic population. In other words, these assays will have significant utility in identifying subjects without clinically detectable CHD disease who are at increased risk to develop CHD and to identify patients with subclinical or clinically established CHD at high risk to have an acute CVD event.  This method of collection, separation and assay of a range of modified LDLs from circulating immune complexes is more consistent, reliable and robust than other previously proposed methods.

Overview: Clinical atherosclerosis affects more than 25 million Americans.  That number does not reflect the substantial portion of the population that has asymptomatic, subclinical atherosclerosis.  According to the NHLBI’s MESA study, subclinical atherosclerotic subjects with coronary artery calcification are four to ten times more likely to experience a coronary event than subjects with no calcification.  Current methods for detecting subclinical atherosclerosis, chest CT or neck ultrasound are costly.  Early identification of high risk patients could target the patient population that requires additional screening and aggressive intervention to minimize irreversible damage such as nephropathy, heart attack and blindness.  Having a reliable, inexpensive method of screening would allow for appropriate adjustments to therapy both early on and over time.

Advantages: More consistent and reliable than other current methods of modified LDL measurement in serum samples, adversely affected by the interference of antigen-antibody complexes (over 90% of modified forms of LDL circulate in the form of IC)

Key Words: Atherosclerosis, modified LDL, subclinical atherosclerosis, cardiovascular disease, diabetes, coronary artery disease

Publications: Virella, Gabriel, et al. "Immunoassay of Modified Forms of Human Low Density Lipoprotein in Isolated Circulating Immune Complexes." Journal of Immunoassay and Immunochemistry 34.1 (2013): 61-74.

Hunt KJ, et al. “Oxidized LDL and AGE-LDL in Circulating Immune Complexes Strongly Predict Progression of Carotid Artery IMT in Type 1 Diabetes.” Atherosclerosis 231(2) (2013): 315-22.

Lopes-Virella MF, et al. “The Levels of MDA-LDL in Circulating Immune Complexes Predict Myocardial Infarction in the VADT Study.” Atherosclerosis 224(2) (2012): 526-31.

Lopes-Virella MF, et al. “Oxidized LDL Immune Complexes and Coronary Artery Calcification in Type 1 Diabetes.” Atherosclerosis 214(2) (2011):462-7.

Lopes-Virella MF, et al. “Levels of Oxidized LDL and Advanced Glycation End Products-Modified LDL in Circulating Immune Complexes are Strongly Associated with Increased Levels of Carotid Intima-Media Thickness and its Progression in Type 1 Diabetes.” Diabetes (2011):582-9.

Inventors: Maria Lopes-Virella and Gabriel Virella

Patent Status:       US Patent 8,568,995 ; US Patent 8,911,958

MUSC-FRD Technology ID: P0923

 

Patent Information:
Category(s):
Diagnostic
For Information, Contact:
Scott Davis
Sr Licensing Manager
MUSC Foundation for Research Development
843-876-1900
davissco@musc.edu
Inventors:
Maria Lopes-Virella
Gabriel Virella
Keywords:
cardiovascular
diagnostic
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