GeneSTAR Research Center - Genetic Studies of Atherosclerosis Risk

Early Identification of Preclinical Coronary Atherosclerosis in High Risk Families
 
GeneSTAR has over 25 years of experience in assessing noninvasive measures of occult preclinical coronary disease including perfusion imaging and coronary angiography. We have shown that the results of perfusion imaging are potent predictors of clinical coronary disease, and of its nature and severity. We have extended this work to CT angiography, examining both calcified and uncalcified plaque, extending the work beyond phenotype-phenotype associations to genomics. More recently we have begun to examine areas of inflammation in the coronary arteries using positron emission tomography with a new agent.
 
 
CT Angiography Studies
 
The prime goal is to compare an innovative coronary artery imaging technology with a standard imaging method in the detection of very early coronary disease in people who are at high risk but who have not had symptoms or a clinical coronary disease event.
 
Coronary atherogenesis begins well before manifest clinical coronary disease (CAD). If occult CAD and its extent could be accurately identified during the preclinical phase, targeted intensive preventive therapies could be tested that may mitigate CAD events. In this study we apply a comparative effectiveness research paradigm to a susceptible population of asymptomatic first degree adult relatives of persons with known premature CAD, all easily identifiable by family history, with a CAD risk that is 2-5 times that of the general population. 
 
The objective is to advance personalized preventive medicine based on early detection of coronary disease and its forms.  We compare CT CAC and MDCTA for identifying latent preclinical CAD in GeneSTAR subjects who represent appropriate targets for intensive preventive therapies. Our aims are to:
 
  • evaluate both the extent of calcified and noncalcified coronary plaque using MDCTA,  and coronary calcium score (CAC) in 1000 22 to 75 year old apparently healthy siblings and adult offspring of probands with known premature CAD (< 60 years of age) from the GeneSTAR study.
  • determine the relationship of traditional risk factors (Framingham Global Risk Score), and hsCRP to outcomes to determine the optimal identification of persons with significant preclinical CAD, and
  • determine whether the addition of known genetic risk variants for CAD improve selection of subjects for CT or MDCTA.
 
Data is being used to generate reference values for plaque volumes and to determine the value of MDCTA as a method to track responsiveness to therapy in primary prevention trials. 

Done in concert with Dr. Elliot Fishman, Director of Johns Hopkins CT Radiology, Drs. Brian Kral and Lewis Becker. spearhead this effort on behalf of the GeneSTAR team. 

New work involves molecular imaging of plaque using PET under the leadership of Dr. Kral with Dr, Martin Pompers and team in Nuclear Medicine.using a novel agent to identify "hot spots" of inflammation in relation to findings of plaque on CT angiography.
 
The ENIGMA study is combined with extensive phenotyping in nuclear perfusion imaging and exercise testing, offering a great opportunity to look at the relationship of lesions on CT angiography and functional changes. Drs. Jay Vaidya and Diane Becker are examining metabolic and traditional and nontraditional risk factors that may be mechanistically involved on various expressions of occult CAD.





Brian G. Kral, MD, MPH
Assistant Professor, Cardiology
ENIGMA, Principal Investigator



Collaborators 

Elliot K Fishman, M.D.
Director of Diagnostic Imaging and Body CT
Professor of Radiology and Radiological Science

Stefan Loy Zimmerman, M.D.
Associate Professor of Radiology and Radiological Science

Martin G. Pomper, M.D., Ph.D.
Director, Nuclear Medicine and Molecular Imaging
Professor of Radiology and Radiological Science