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

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

Abstract

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.

Keywords: GWAS; LDL-cholesterol; cardiovascular risk; coronary artery disease; genetic risk score.

Figures

Figure 1
Figure 1
CONSORT flow diagram.

References

    1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics – 2015 update: a report from the American Heart Association. Circulation (2015) 131(4):e29–322.10.1161/CIR.0000000000000152
    1. Ellis JJ, Erickson SR, Stevenson JG, Bernstein SJ, Stiles RA, Fendrick AM. Suboptimal statin adherence and discontinuation in primary and secondary prevention populations. J Gen Intern Med (2004) 19(6):638–45.10.1111/j.1525-1497.2004.30516.x
    1. Tang L, Patao C, Chuang J, Wong ND. 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). Am J Cardiol (2013) 112(8):1126–32.10.1016/j.amjcard.2013.05.064
    1. Iqbal J, Zhang YJ, Holmes DR, Morice MC, Mack MJ, Kappetein AP, 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 follow-up. Circulation (2015) 131(14):1269–77.10.1161/CIRCULATIONAHA.114.013042
    1. Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med (2000) 343(1):16–22.10.1056/NEJM200007063430103
    1. Tikkanen E, Havulinna AS, Palotie A, Salomaa V, Ripatti S. Genetic risk prediction and a 2-stage risk screening strategy for coronary heart disease. Arterioscler Thromb Vasc Biol (2013) 33(9):2261–6.10.1161/ATVBAHA.112.301120
    1. Ganna A, Magnusson PK, Pedersen NL, de Faire U, Reilly M, Arnlöv J, et al. Multilocus genetic risk scores for coronary heart disease prediction. Arterioscler Thromb Vasc Biol (2013) 33(9):2267–72.10.1161/ATVBAHA.113.301218
    1. Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield M, Devlin JJ, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet (2015) 385(9984):2264–71.10.1016/S0140-6736(14)61730-X
    1. Tada H, Melander O, Louie JZ, Catanese JJ, Rowland CM, Devlin JJ, et al. Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history. Eur Heart J (2016) 37(6):561–7.10.1093/eurheartj/ehv462
    1. Joseph PG, Pare G, Asma S, Engert JC, Yusuf S, Anand SS, et al. Impact of a genetic risk score on myocardial infarction risk across different ethnic populations. Can J Cardiol (2016) 32(12):1440–6.10.1016/j.cjca.2016.05.014
    1. Voils CI, Coffman CJ, Grubber JM, Edelman D, Sadeghpour A, Maciejewski ML, et al. Does type 2 diabetes genetic testing and counseling reduce modifiable risk factors? A randomized controlled trial of veterans. J Gen Intern Med (2015) 30(11):1591–8.10.1007/s11606-015-3315-5
    1. Kullo IJ, Jouni H, Austin EE, Brown SA, Kruisselbrink TM, Isseh IN, 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). Circulation (2016) 133(12):1181–8.10.1161/CIRCULATIONAHA.115.020109
    1. Knowles JW, Assimes TL, Kiernan M, Pavlovic A, Goldstein BA, Yank V, et al. Randomized trial of personal genomics for preventive cardiology: design and challenges. Circ Cardiovasc Genet (2012) 5(3):368–76.10.1161/CIRCGENETICS.112.962746
    1. Vargas JD, Manichaikul A, Wang XQ, Rich SS, Rotter JI, Post WS, et al. Common genetic variants and subclinical atherosclerosis: the multi-ethnic study of atherosclerosis (MESA). Atherosclerosis (2016) 245:230–6.10.1016/j.atherosclerosis.2015.11.034
    1. Coronary Artery Disease (C4D) Genetics Consortium. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat Genet (2011) 43(4):339–44.10.1038/ng.782
    1. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, 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. Circulation (2014) 129(25 Suppl 2):S1–45.10.1161/01.cir.0000437738.63853.7a
    1. Goldstein BA, Knowles JW, Salfati E, Ioannidis JP, Assimes TL. Simple, standardized incorporation of genetic risk into non-genetic risk prediction tools for complex traits: coronary heart disease as an example. Front Genet (2014) 5:254.10.3389/fgene.2014.00254
    1. Hollands GJ, French DP, Griffin SJ, Prevost AT, Sutton S, King S, et al. The impact of communicating genetic risks of disease on risk-reducing health behaviour: systematic review with meta-analysis. BMJ (2016) 352:i1102.10.1136/bmj.i1102
    1. Bloss CS, Schork NJ, Topol EJ. Effect of direct-to-consumer genomewide profiling to assess disease risk. N Engl J Med (2011) 364(6):524–34.10.1056/NEJMoa1011893
    1. Lederman J, Ballard J, Njike VY, Margolies L, Katz DL. Information given to postmenopausal women on coronary computed tomography may influence cardiac risk reduction efforts. J Clin Epidemiol (2007) 60(4):389–96.10.1016/j.jclinepi.2006.07.010
    1. Mamudu HM, Paul TK, Veeranki SP, Budoff M. The effects of coronary artery calcium screening on behavioral modification, risk perception, and medication adherence among asymptomatic adults: a systematic review. Atherosclerosis (2014) 236(2):338–50.10.1016/j.atherosclerosis.2014.07.022
    1. Kalia NK, Cespedes L, Youssef G, Li D, Budoff MJ. Motivational effects of coronary artery calcium scores on statin adherence and weight loss. Coron Artery Dis (2015) 26(3):225–30.10.1097/MCA.0000000000000207
    1. Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG, Cook NR, et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med (2016) 375(24):2349–58.10.1056/NEJMoa1605086
    1. Kiernan M, Schoffman DE, Lee K, Brown SD, Fair JM, Perri MG, et al. The Stanford leisure-time activity categorical item (L-Cat): a single categorical item sensitive to physical activity changes in overweight/obese women. Int J Obes (Lond) (2013) 37(12):1597–602.10.1038/ijo.2013.36

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅