Multi-Analyte, Genetic, and Thrombogenic Markers of Atherosclerosis (The MAGMA STUDY)

Cardiovascular diseases (CVD), primarily coronary artery disease are the leading cause of death and disability in the United States and Europe. The cost of cardiovascular disease in the United States in 2009 is estimated to be $475.3 billion, according to the American Heart Association and the National Heart, Lung, and Blood Institute. Although there have been significant accomplishments in reducing cardiovascular events over the past decade, too many people still die of heart and vascular diseases. Therefore, the improvement of risk stratification of CVD by identification of new biomarkers has been extensively investigated in both primary and secondary clinical settings in the past decade. A substantial number of biomarkers, representing various stages of atherogenesis and impaired cardiac function, have been evaluated against modifiable traditional risk factors, such as cholesterol, blood pressure, smoking status, and diabetes. However, little is known about the true extent that these identified multi-analyte, genetic, and thrombogenic markers contribute to the presence and degree of atherosclerosis.

Patients with severe stenosis of coronary arteries may have a different profile of biochemical and genetic markers than patients with "clear" coronary vessels. Therefore, more research is required to improve the predictability and specificity of these known and novel factors before physicians fully implement these tests into their routine clinical practice.

At present, physicians rely on conventional cardiovascular risk factors to try to identify at-risk patients. A number of risk factors stem from genetic or biologic conditions such as gender, age, ethnicity and family history of heart disease. While many risk factors cannot be changed, risk factors such as high cholesterol, high blood pressure, obesity, tobacco smoking, stress, physical inactivity can be modified. One of the most significant risk factor for the development of CVD is diabetes mellitus, whereby both heredity and lifestyle play a major role. Nevertheless, there are patients without these known classical risk factors who develop severe CVD. Conversely, there are patients with these classical risk factors without relevant coronary artery disease. "The CVD Risk Factor Paradox" may be explained by a combination of biological, environmental, and genetic factors that are under investigation.

Animal and human studies have established the role of cholesterol in the development and progression of atherosclerosis. Epidemiological studies directly implicated LDL-C to the development of atherosclerosis and CVD. Furthermore, LDL-C level appears to be directly related to the development and recurrence of CVD. While LDL-C is the primary lipid marker for assessing risk, evidence has demonstrated the important role of other lipoproteins components in atherogenesis. These include lipoprotein (a), LDL pattern density, HDL subtypes, VLDL, and intermediate-density lipoprotein. A substantial body of evidence has also demonstrated Lp-PLA2 as a cardiovascular risk marker in both primary and secondary prevention that provides new information, over and above new traditional risk factors. Most recently oxidized low-density lipoprotein (oxLDL)/ β2-glycoprotein I (β2GPI) complexes have been implicated in atherogenesis. More accurate and expanded depiction of the lipid profile compared to the standard lipid profile may identify important emerging risk factors and secondary targets of therapy for cardiovascular disease.

It is also been established that heightened plaque metabolism together with increased blood vulnerability characterized by hypercoagulability, heightened platelet reactivity and inflammation, are important processes responsible for plaque rupture and subsequent occlusive ischemic events occurrence during ACS. Recent developments in catheter-based near-infrared spectroscopy may help to identify vulnerable plaques by characterizing chemical components. However, information regarding blood vulnerability based on a specific biomarker profile is lacking.