The clinical utility and cost-effectiveness of cardiovascular genetic risk testing for targeting statin therapy in the primary prevention of atherosclerotic cardiovascular disease Public Deposited

Downloadable Content

Download PDF
Last Modified
  • March 20, 2019
Creator
  • Jarmul, Jamie
    • Affiliation: Gillings School of Global Public Health, Department of Health Policy and Management
Abstract
  • This three-paper dissertation examined the clinical utility and cost-effectiveness of testing for cardiovascular genetic risk, using a previously developed 27-SNP cardiovascular genetic risk score (cGRS), to target statin therapy in the primary prevention of atherosclerotic cardiovascular disease (ASCVD). In the first paper, I tested the association between the 27-SNP cGRS and 10-year ASCVD outcomes in black and white non-diabetic, ASCVD-free participants from the ARIC study. After adjusting for traditional ASCVD risk factors, I found that intermediate and high cGRS was associated with a 1.32-fold (95% CI: 0.97-1.79) and 1.47-fold (95% CI: 1.03-2.10) higher risk of 10-year pooled ASCVD events, respectively; however, the improvement in risk prediction was small. In the second paper, I used an unbiased model selection algorithm with 10-fold cross-validation to determine the expected distribution of the 27-SNP cGRS in a multi-ethnic, nationally representative sample of individuals, the Add Health study. I found that race/ethnicity was the only statistically significant predictor of cGRS, explaining a fair amount of the variation (CV r2= 0.177), and that the risk increase associated with high expected cGRS was modest (approximately 30% increase in 10-year predicted ASCVD risk, comparable to the risk increase associated with being 5 years older). In the third paper, I updated the UNC-RTI CHD Prevention Model to investigate whether testing for the 27-SNP cGRS is a cost-effective strategy for targeting statin therapy in the primary prevention of ASCVD. I found that obtaining a 27-SNP cGRS test to prevent some patients from being prescribed a statin was generally not a cost-effective strategy for a set of clinical scenarios of individuals with 10-year predicted ASCVD risk ranging from 2.5% to 7.5%. In conclusion, I found that a 27-SNP cGRS is independently associated with 10-year ASCVD outcomes in a diverse population; however, the absolute change in updated 10-year ASCVD predicted risk estimates is modest. More importantly, through the work completed in the dissertation, I can conclude that, when compared to no genetic risk testing, obtaining cardiovascular genetic risk information by testing for a 27-SNP cGRS is generally not a cost-effective strategy for targeting statin therapy in the primary prevention of ASCVD.
Date of publication
Keyword
DOI
Resource type
Rights statement
  • In Copyright
Advisor
  • Hassmiller Lich, Kristen
  • Avery, Christy
  • Pignone, Michael
  • Weinberger, Morris
  • Wheeler, Stephanie
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
Language
Parents:

This work has no parents.

Items