Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates

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 old, at intermediate risk for CHD, and not on statins) were randomized 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 (+H-GRS) or average/low (+L-GRS) GRS. Risk was disclosed by a genetic counselor followed by shared decision-making regarding statin therapy with a physician. We compared the primary endpoint of LDL-C levels at 6 months and assessed whether any differences were due 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 vs. 105.9{+/-}33.3 mg/dL; P=0.04). +H-GRS participants had lower LDL-C levels (92.3{+/-}32.9 mg/dL) than CRS participants (P=0.02) but not +L-GRS participants (100.9{+/-}32.2 mg/dL; P=0.18). Statins were initiated more often in the +GRS group than in the CRS group (39% vs. 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 Information--ClinicalTrials.gov. Identifier: NCT01936675.