Incorporating a genetic risk score into coronary heart disease risk estimates: Effect on low-density lipoprotein cholesterol levels (the MI-GENES Clinical Trial)

Iftikhar J. Kullo, Hayan Jouni, Erin E. Austin, Sherry Ann Brown, Teresa M. Kruisselbrink, Iyad N. Isseh, Raad A. Haddad, Tariq S. Marroush, Khader Shameer, Janet E. Olson, Ulrich Broeckel, Robert C. Green, Daniel J. Schaid, Victor M. Montori, Kent R. Bailey

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

Background - Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results - Participants (n=203, 45-65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS (+GRS). Participants in the +GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or +GRS (n=103). At the end of the study period, the +GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not participants with low GRS (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the +GRS group than in the CRS group (39% versus 22%, P<0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions - Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936675.

Original languageEnglish (US)
Pages (from-to)1181-1188
Number of pages8
JournalCirculation
Volume133
Issue number12
DOIs
StatePublished - Mar 22 2016

Keywords

  • coronary disease
  • genetic risk disclosure
  • genetic risk score
  • genomics
  • hydroxymethylglutaryl-CoA reductase inhibitors
  • polymorphism, single-nucleotide
  • prevention & control
  • randomized clinical trials

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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