New Data Published in an American Heart Association Journal Shows That Lipoprotein-Associated Phospholipase A2 Independently Adds to the Diagnostic Accuracy of Traditional Risk Assessment for Future Cardiovascular Events.

SOUTH SAN FRANCISCO, Calif. -- KAROLA Study Confirms Lp-PLA2 as Key Independent Cardiovascular Biomarker

diaDexus today announced that new data published in the American Heart Association's journal Arteriosclerosis, Thrombosis, and Vascular Biology showed that coronary heart disease (CHD) patients with the highest levels of the enzyme Lp-PLA2 were more than twice as likely to have a recurrent cardiovascular event, whereas 95% of the patients with the lowest levels of the enzyme remained event-free over four years of follow up. The study was led by Dr. Wolfgang Koenig, Department of Internal Medicine II -- Cardiology, University of Ulm Medical Center, Ulm, Germany.

"Several large prospective studies have shown that Lp-PLA2 is an independent cardiovascular biomarker in initially healthy subjects," Dr. Koenig said. "In this study we wanted to determine whether levels of Lp-PLA2 provide additional prognostic information for future cardiovascular events in a large cohort of high-risk patients."

Results showed that in multivariable analyses, Lp-PLA2 was strongly associated with cardiovascular disease (CVD) events, including stroke and heart attack, even after accounting for multiple covariates that included age, gender, hospital site, smoking status, history of MI, history of diabetes mellitus, cystatin C, intake of ACE-inhibitors, HDL-cholesterol, treatment with lipid-lowering drugs, NT-proBNP and LDL-cholesterol. The hazard ratio (HR) for recurrent events in the top tertile of Lp-PLA2 mass distribution was 2.09 (95% CI, 1.10-3.96) compared with the bottom tertile. Further analysis found that Lp-PLA2 moves the area under the curve (AUC), demonstrating an improvement in predictive accuracy, even after addition of traditional risk factors and the novel biomarkers cystatin C and NT-proBNP.

"Improving the area under the curve is an important indicator of a clinically relevant diagnostic test since it indicates that the test improves the accuracy in separating affected from unaffected patients," said Bob Wolfert, vice president of diagnostics, diaDexus. "The fact that Lp-PLA2 independently adds to the area under the curve means that it adds value to the current diagnostic paradigm in cardiovascular disease. Data from this study underscore the value of Lp-PLA2 as an independent risk factor that can help physicians stratify their high-risk patients into a very high-risk category."

Study Details

The study enrolled 1,206 patients, aged 30-70, with a diagnosis of CHD within the past three months who were taking part in an in-hospital rehabilitation program. In Germany, all patients after acute coronary syndrome or coronary artery revascularization are offered a comprehensive in-hospital rehabilitation and lifestyle improvement program after discharge from the acute care hospital. At the beginning of the in-hospital rehabilitation program, all subjects filled out a standardized questionnaire containing sociodemographic information and medical history. In addition, information was taken from the patients' hospital charts. Plasma concentrations and activity of Lp-PLA2 were determined at baseline for 1,051 patients (87.2%), in whom complete follow-up information was available. A total of 95 (9.0%) secondary fatal and non-fatal CVD events (30 cardiovascular deaths, 35 non-fatal MIs and 30 strokes) occurred during a mean follow-up of 48.7 months. A Cox proportional hazards model was used to determine the prognostic value of Lp-PLA2 after adjustment for multiple covariates. Lp-PLA2 was determined using the commercially available PLAC(R) Test supplied by diaDexus, South San Francisco, Calif.

About diaDexus

diaDexus, Inc., a privately held biotechnology company based in South San Francisco, Calif., is focused on the discovery, development and commercialization of novel, patent-protected diagnostic products with high clinical value. The PLAC(R) test, developed by diaDexus, is a blood test cleared by the U.S. Food and Drug Administration to aid in the prediction of an individual's risk for coronary heart disease or ischemic stroke event, in conjunction with clinical evaluation and patient risk assessment. For more information about the PLAC(R) test visit www.plactest.com. More information about the company may be found at www.diaDexus.com.