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

Purpose 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. Methods 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. Results 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. Conclusion 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.

[1]  P. Natarajan Polygenic Risk Scoring for Coronary Heart Disease: The First Risk Factor. , 2018, Journal of the American College of Cardiology.

[2]  E. Ashley,et al.  Cardiovascular Precision Medicine in the Genomics Era , 2018, JACC. Basic to translational science.

[3]  M. Caulfield,et al.  Hypertension genomics and cardiovascular prevention. , 2018, Annals of translational medicine.

[4]  S. Yusuf,et al.  Impact of a Genetic Risk Score on Myocardial Infarction Risk Across Different Ethnic Populations. , 2016, The Canadian journal of cardiology.

[5]  E. Boerwinkle,et al.  Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. , 2016, The New England journal of medicine.

[6]  T. Marteau,et al.  The impact of communicating genetic risks of disease on risk-reducing health behaviour: systematic review with meta-analysis , 2016, British Medical Journal.

[7]  R. Green,et al.  Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates: Effect on Low-Density Lipoprotein Cholesterol Levels (the MI-GENES Clinical Trial). , 2016, Circulation.

[8]  David A Bluemke,et al.  Common genetic variants and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA). , 2016, Atherosclerosis.

[9]  J. Catanese,et al.  Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history , 2015, European heart journal.

[10]  Olle Melander,et al.  Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials , 2015, The Lancet.

[11]  M. Budoff,et al.  Motivational effects of coronary artery calcium scores on statin adherence and weight loss , 2015, Coronary artery disease.

[12]  G. Ginsburg,et al.  Does Type 2 Diabetes Genetic Testing and Counseling Reduce Modifiable Risk Factors? A Randomized Controlled Trial of Veterans , 2015, Journal of General Internal Medicine.

[13]  E. Steyerberg,et al.  Optimal Medical Therapy Improves Clinical Outcomes in Patients Undergoing Revascularization With Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting: Insights From the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial at the 5-Year Fol , 2015, Circulation.

[14]  M. Budoff,et al.  The effects of coronary artery calcium screening on behavioral modification, risk perception, and medication adherence among asymptomatic adults: a systematic review. , 2014, Atherosclerosis.

[15]  John P. A. Ioannidis,et al.  Simple, standardized incorporation of genetic risk into non-genetic risk prediction tools for complex traits: coronary heart disease as an example , 2014, Front. Genet..

[16]  Jennifer G. Robinson,et al.  2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines , 2014, Journal of the American College of Cardiology.

[17]  Jennifer G. Robinson,et al.  2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. , 2014, Circulation.

[18]  N. Wong,et al.  Cardiovascular risk factor control and adherence to recommended lifestyle and medical therapies in persons with coronary heart disease (from the National Health and Nutrition Examination Survey 2007-2010). , 2013, The American journal of cardiology.

[19]  E. Ingelsson,et al.  Multilocus Genetic Risk Scores for Coronary Heart Disease Prediction , 2013, Arteriosclerosis, thrombosis, and vascular biology.

[20]  V. Salomaa,et al.  Genetic Risk Prediction and a 2-Stage Risk Screening Strategy for Coronary Heart Disease , 2013, Arteriosclerosis, thrombosis, and vascular biology.

[21]  Danielle E. Schoffman,et al.  The Stanford Leisure-Time Activity Categorical Item (L-Cat): a single categorical item sensitive to physical activity changes in overweight/obese women , 2013, International Journal of Obesity.

[22]  D. Absher,et al.  Randomized Trial of Personal Genomics for Preventive Cardiology: Design and Challenges , 2012, Circulation. Cardiovascular genetics.

[23]  N. Schork,et al.  Effect of direct-to-consumer genomewide profiling to assess disease risk. , 2011, The New England journal of medicine.

[24]  Mark I. McCarthy,et al.  A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease , 2011, Nature Genetics.

[25]  Mark D. Huffman,et al.  Heart Disease and Stroke Statistics—2015 Update: A Report From the American Heart Association , 2009, Circulation.

[26]  V. Njike,et al.  Information given to postmenopausal women on coronary computed tomography may influence cardiac risk reduction efforts. , 2007, Journal of clinical epidemiology.

[27]  A. Fendrick,et al.  Suboptimal statin adherence and discontinuation in primary and secondary prevention populations , 2004, Journal of General Internal Medicine.

[28]  F. Rank,et al.  PRIMARY PREVENTION OF CORONARY HEART DISEASE IN WOMEN THROUGH DIET AND LIFESTYLE , 2000 .