Faculty Collaboration Database

Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates: Effect on Low-Density Lipoprotein Cholesterol Levels (the MI-GENES Clinical Trial). Circulation 2016 Mar 22;133(12):1181-8

Date

02/27/2016

Pubmed ID

26915630

Pubmed Central ID

PMC4803581

DOI

10.1161/CIRCULATIONAHA.115.020109

Scopus ID

2-s2.0-84959230547 (requires institutional sign-in at Scopus site)   182 Citations

Abstract

BACKGROUND: Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels.

METHODS AND RESULTS: Participants (n=203, 45-65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS ((+)GRS). Participants in the (+)GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or (+)GRS (n=103). At the end of the study period, the (+)GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not participants with low GRS (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the (+)GRS group than in the CRS group (39% versus 22%, P<0.01). No significant differences in dietary fat intake and physical activity levels were noted.

CONCLUSIONS: Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone.

CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936675.

Author List

Kullo IJ, Jouni H, Austin EE, Brown SA, Kruisselbrink TM, Isseh IN, Haddad RA, Marroush TS, Shameer K, Olson JE, Broeckel U, Green RC, Schaid DJ, Montori VM, Bailey KR

Author

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Anxiety
Cholesterol, LDL
Comorbidity
Coronary Disease
Decision Making
Dietary Fats
Female
Follow-Up Studies
Genetic Counseling
Genetic Predisposition to Disease
Genotype
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Male
Middle Aged
Minnesota
Motor Activity
Patient Participation
Physician-Patient Relations
Polymorphism, Single Nucleotide
Probability
Risk Assessment
Risk Factors