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Safarova MS, Bailey KR, Kullo IJ. Association of a Family History of Coronary Heart Disease With Initiation of Statin Therapy in Individuals at Intermediate Risk: Post Hoc Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2016;1(3):364–366. doi:10.1001/jamacardio.2016.0227
Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
A family history of coronary heart disease (CHD) is associated with an approximately 1.5- to 2.0-fold higher risk of CHD independent of conventional risk factors,1 highlighting the contribution of genetic factors to disease susceptibility. Whether discussion of risk associated with a family history of CHD influences shared decision making regarding statin initiation is unknown. The Myocardial Infarction-GENES (MI-GENES) study2-4 tested the hypothesis that incorporating a multilocus genetic risk score (GRS) into CHD risk estimates would be associated with lower low-density lipoprotein cholesterol levels. We conducted a post hoc analysis to assess whether disclosure of risk associated with a family history of CHD was associated with initiation of statin therapy.
Between October 9, 2013, and April 28, 2014, residents of Olmsted County, Minnesota, at intermediate risk for CHD and not receiving statin therapy were randomized 1:1 to either a conventional (Framingham) risk score (FRS)5 alone or FRS supplemented with a GRS. Family history was defined as the presence of CHD (ie, angina, myocardial infarction, or myocardial revascularization) in a first-degree male or female relative (ie, parents, siblings, and children) before age 55 or 65 years, respectively. A GRS was calculated based on genotypes at 28 CHD susceptibility loci.6 The 10-year risk of CHD was disclosed by a genetic counselor informing participants of a 1.5- to 2.0-fold higher risk in the presence of family history, followed by shared decision making regarding statin therapy with a physician. The study protocol was approved by the Mayo Clinic institutional review board. All participants gave written informed consent; financial compensation was provided.
Participants returned at 3 and 6 months after risk disclosure for measurement of low-density lipoprotein cholesterol levels and assessment of statin use, dietary fat consumption (scores ranged between 0 [no fat intake] to 110 indicative of very high dietary fat intake as measured by the fat screener7), and physical activity levels (scores ranged between 7 [active] and 1 [sedentary] based on the adapted version of telephonic assessment of a physical activity questionnaire).8 Continuous or dichotomous variables were compared between groups using a 2-sample t test or a χ2 test, respectively. We compared the rate of statin initiation between participants with and those without a family history of CHD using logistic regression, also adjusting for allocation to GRS. We tested the association of GRS with family history, using t tests with significance set at P < .05. A paired difference test was used to assess changes over time within each group. A comparison between the groups was performed using an unpaired t test. All analyses were performed in JMP Pro, version 10.0.0 (SAS Institute Inc). Data analysis was conducted from September 26, 2015, to January 10, 2016.
Participant characteristics did not differ significantly between groups (Table 1). Both the GRS and FRS tended to be higher in participants with a family history of CHD but the 2 measures were not correlated (r = 0.01; P = .85). No difference in self-reported fat intake and physical activity was noted between participants with and those without a family history of CHD.
Of individuals with a family history of CHD, 26 (47.3%) began statin therapy compared with 42 (28.4%) of those without a family history (χ2 = 6.43; P = .01). Among participants who received a GRS, statin therapy was also more frequent in those with than in those without a family history of CHD (16 [64.0%] vs 26 [33.3%], P = .007). Disclosure of a GRS resulted in a higher rate of statin prescriptions (16 [64.0%] vs 10 [33.3%]; P = .02) among individuals with a family history of CHD than in those who received only an FRS (Table 2). In a 2-variable model (odds ratio [95% CI]), both family history (2.46 [1.28-4.76]; P < .01) and allocation to GRS (2.13 [1.16-3.97]; P = .01) were associated with greater frequency of statin initiation.
To our knowledge, this study is the first to demonstrate that discussion of risk associated with a family history of CHD influences shared decision making regarding statin treatment in intermediate-risk individuals. Among participants with a family history of CHD, disclosure of a GRS was associated with a greater initiation of statins than was disclosure of an FRS alone, suggesting that quantitative genetic risk information additionally influences shared decision making regarding statin therapy. This study was not powered to detect a difference in low-density lipoprotein cholesterol levels between participants with and those without a family history of CHD.
The GRS was not significantly higher in participants with a family history of CHD, suggesting that family history and a GRS may provide additive CHD risk information. Additional studies are needed to investigate whether disclosing risk associated with family history leads to greater adherence to treatment and improved outcomes.
Disclosure of CHD risk that includes discussion of family history influences shared decision making regarding statin therapy in individuals at intermediate risk for CHD.
Corresponding Author: Iftikhar J. Kullo, MD, Department of Cardiovascular Diseases, Mayo Clinic, Stabile Bldg 4-52, 200 First St, SW, Rochester, MN 55905 (firstname.lastname@example.org).
Published Online: April 13, 2016. doi:10.1001/jamacardio.2016.0227.
Author Contributions: Drs Safarova and Kullo had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Kullo.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Safarova, Kullo.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Safarova, Bailey.
Obtained funding: Kullo.
Administrative, technical, or material support: Kullo.
Study supervision: Kullo.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kullo receives compensation as a member of the speaker’s bureau for Amgen. No other disclosures were reported.
Funding/Support: This work was supported by the National Human Genome Research Institute’s electronic Medical Records and Genomics Network through grants HG04599 and HG006379 to Mayo Clinic. Dr Safarova is funded by American Heart Association Postdoctoral Fellowship Award 16POST27280004.
Role of the Funder/Sponsor: The National Human Genome Research Institute and American Heart Association had no role in the design and conduct of the work; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We are indebted to the participants of the MI-GENES study and to the staff of Cardiovascular Health Clinic, Mayo Clinic.
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