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

Joshua W. Knowles,Devin Absher,Aleksandra Pavlovic,Michael V. McConnell,Jin Li,John P. A. Ioannidis,Benjamin A. Goldstein,Michaela Kiernan,Euan A. Ashley,Shirin Zarafshar,Themistocles L. Assimes,Sandra Tsai

doi:10.3389/fcvm.2017.00053

Abstract

We 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. We 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. Sixty-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. Adding 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.

Highlights

Coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide [1]
Emerging data suggest that a genetic risk score (GRS) modestly improves risk prediction beyond traditional risk factors included in widely used clinical risk scores such as the Framingham or Omnibus risk estimator [6,7,8,9]
The clinical utility of these observations remains unclear in the absence of randomized trials that directly document a clinical benefit given the degree of incremental improvement of risk prediction provided by the GRS remains quite modest [6,7,8,9]

Summary

Introduction

Coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide [1]. Prior studies have shown poor adherence to statins in both primary and secondary prevention populations with discontinuation rates of up to ~40% [2,3,4]. Other studies such the Nurses’ Health study have documented a high population-attributable risk of CAD events related to suboptimal diet, physical activity, diet, and smoking patterns [5]. The clinical utility of these observations remains unclear in the absence of randomized trials that directly document a clinical benefit (e.g., reduction in CAD events through the incorporation of a GRS) given the degree of incremental improvement of risk prediction provided by the GRS remains quite modest [6,7,8,9]

Methods

Results

Conclusion