In our proposed study, SBHW-PREDICT (The role of PRoteomics, gEnetics, and Directed Imaging using CT), we will assess whether identification of at-risk individuals, using imaging markers, a biomarker profile or a combination of the two, improves reclassification and discrimination over traditional risk factors, particularly in those wth either a family history of coronary heart disease (CHD) or higher genetic predisposition for CHD. We have used data from 1312 participants of the first NIH-funded study of predictive value of CAC, the South Bay Heart Watch (SBHW) study, to calculate plaque density. In preliminary analyses, we have found that higher plaque density is related to lower incidence of CVD events in this cohort. In the proposed study, we will use serum and cell samples collected at baseline, 20 years ago, from the SBHW and retrospectively assess outcomes using administrative data from Medicare and the National Death Index to address the following aims and objectives: 1) Using Medicare Claims and National Death Index data assess prognostic value of baseline CAC, as well as coronary calcium density for long-term (20 year) CHD event rate; 2) Using serum and cell samples collected at baseline, assess whether a multi-biomarker approach using circulating markers from different biological pathways would have additional reclassification value over traditional risk factors; 3) Determine whether compared to family history a CHD genetic risk score is more predictive of events; and 4) Determine whether a genetic score modifies the prognostic value of an imaging marker (CAC) or a multiple biomarker score or a combination of the two in those at higher predisposition (based on either family history or genetic score) for CHD versus those at low genetic risk. The experience of our multidisciplinary research team, unique 20 year follow-up period after baseline CAC, linkage to Medicare claims data and Death Index data, genetic and biomarker profiles using frozen serum and cell samples, and follow-up of the original cohort survivors are major strengths of this proposal. Results of thi project will assess the utility of a complementary genetic marker, multi-biomarker, and imaging approach to risk assessment.

Public Health Relevance

Developing ways to better predict those who will have a heart attack or die from heart disease is important in prevention. We will examine how blood tests, genetic tests, and imaging tests of the heart can predict over a long period of time who will develop heart disease. If successful, this study could offer new ways of finding those individuals who are at greatest risk of heart attacks or death from heart disease and who may benefit from early treatment that could help them prevent heart disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL128801-02
Application #
9109508
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Papanicolaou, George
Project Start
2015-07-15
Project End
2020-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92617
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