Impact of a Genetic Risk Score for Coronary Artery Disease on Reducing Cardiovascular Risk: A Pilot Randomized Controlled Study

Abstract

PurposeWe tested whether providing a genetic risk score (GRS) for coronary artery disease (CAD) would serve as a motivator to improve adherence to risk-reducing strategies.MethodsWe randomized 94 participants with at least moderate risk of CAD to receive standard-of-care with (N = 49) or without (N = 45) their GRS at a subsequent 3-month follow-up visit. Our primary outcome was change in low density lipoprotein cholesterol (LDL-C) between the 3- and 6-month follow-up visits (ΔLDL-C). Secondary outcomes included other CAD risk factors, weight loss, diet, physical activity, risk perceptions, and psychological outcomes. In pre-specified analyses, we examined whether there was a greater motivational effect in participants with a higher GRS.ResultsSixty-five participants completed the protocol including 30 participants in the GRS arm. We found no change in the primary outcome between participants receiving their GRS and standard-of-care participants (ΔLDL-C: −13 vs. −9 mg/dl). Among participants with a higher GRS, we observed modest effects on weight loss and physical activity. All other secondary outcomes were not significantly different, including anxiety and worry.ConclusionAdding GRS to standard-of-care did not change lipids, adherence, or psychological outcomes. Potential modest benefits in weight loss and physical activity for participants with high GRS need to be validated in larger trials.

Cardiovascular disease: The rise of the genetic risk score

“…While there remains an additional cost for genetic scores, albeit modest, it is reasonable to require an outcome benefit to be demonstrated before arguing for adding to medical expenditure. In a small pilot randomized controlled study, we showed the feasibility of delivery of a genetic risk score in a clinical environment [ 35 – 37 ]. While we did not demonstrate that the score led to an improvement in patient adherence to guideline-based therapeutic advice, others have shown that the incorporation of a genetic risk score into clinical care may increase statin usage (mostly through increased statin prescriptions) [ 38 ].…”

Promises and perils of using genetic tests to predict risk of disease

“…A review of 18 trials in which people were informed of their genetic risk of various diseases showed no effects on smoking, diet, physical activity, alcohol use, or participation in screening and behavioural support programmes 36. More recent trials using polygenic risk scores to identify those at higher risk of developing diabetes or cardiovascular disease have not fared much better 3738. The premise that having more genetic information motivates people to alter risky behaviours remains unproven 39…”

Cardiovascular Precision Medicine in the Genomics Era

“…Although the MI-GENES study could not differentiate between effect on the patient versus effect on the health care provider, a more recent study by Knowles et al. (39) looked at the usefulness of GRS as a motivational tool for reducing CAD risk factors. Patients who received standard-of-care plus GRS showed no significant changes, including medication use, blood pressure, physical activity, weight, and high-density lipoprotein concentration compared with standard-of-care patients (39) .…”