Incorporating a Genetic Risk Score into Coronary Heart Disease Risk Estimates: Effect on LDL Cholesterol Levels (the MIGENES Clinical Trial)

Iftikhar Jan 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 Manuel Montori, Kent R Bailey

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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 old, at intermediate risk for CHD, and not on statins) were randomized 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 (H-GRS) or average/low (L-GRS) GRS. Risk was disclosed by a genetic counselor followed by shared decision-making regarding statin therapy with a physician. We compared the primary endpoint of LDL-C levels at 6 months and assessed whether any differences were due 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 vs. 105.9±33.3 mg/dL; P=0.04). H-GRS participants had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not L-GRS participants (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the GRS group than in the CRS group (39% vs. 22%, P

Original languageEnglish (US)
JournalCirculation
DOIs
StateAccepted/In press - Feb 26 2016

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LDL Cholesterol
Coronary Disease
Clinical Trials
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Dietary Fats

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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Incorporating a Genetic Risk Score into Coronary Heart Disease Risk Estimates : Effect on LDL Cholesterol Levels (the MIGENES Clinical Trial). / Kullo, Iftikhar Jan; Jouni, Hayan; Austin, Erin E.; Brown, Sherry Ann; Kruisselbrink, Teresa M.; Isseh, Iyad N.; Haddad, Raad A.; Marroush, Tariq S.; Shameer, Khader; Olson, Janet E; Broeckel, Ulrich; Green, Robert C.; Schaid, Daniel J; Montori, Victor Manuel; Bailey, Kent R.

In: Circulation, 26.02.2016.

Research output: Contribution to journalArticle

Kullo, Iftikhar Jan ; Jouni, Hayan ; Austin, Erin E. ; Brown, Sherry Ann ; Kruisselbrink, Teresa M. ; Isseh, Iyad N. ; Haddad, Raad A. ; Marroush, Tariq S. ; Shameer, Khader ; Olson, Janet E ; Broeckel, Ulrich ; Green, Robert C. ; Schaid, Daniel J ; Montori, Victor Manuel ; Bailey, Kent R. / Incorporating a Genetic Risk Score into Coronary Heart Disease Risk Estimates : Effect on LDL Cholesterol Levels (the MIGENES Clinical Trial). In: Circulation. 2016.
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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 old, at intermediate risk for CHD, and not on statins) were randomized 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 (H-GRS) or average/low (L-GRS) GRS. Risk was disclosed by a genetic counselor followed by shared decision-making regarding statin therapy with a physician. We compared the primary endpoint of LDL-C levels at 6 months and assessed whether any differences were due 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 vs. 105.9±33.3 mg/dL; P=0.04). H-GRS participants had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not L-GRS participants (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the GRS group than in the CRS group (39{\%} vs. 22{\%}, P",
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T2 - Effect on LDL Cholesterol Levels (the MIGENES Clinical Trial)

AU - Kullo, Iftikhar Jan

AU - Jouni, Hayan

AU - Austin, Erin E.

AU - Brown, Sherry Ann

AU - Kruisselbrink, Teresa M.

AU - Isseh, Iyad N.

AU - Haddad, Raad A.

AU - Marroush, Tariq S.

AU - Shameer, Khader

AU - Olson, Janet E

AU - Broeckel, Ulrich

AU - Green, Robert C.

AU - Schaid, Daniel J

AU - Montori, Victor Manuel

AU - Bailey, Kent R

PY - 2016/2/26

Y1 - 2016/2/26

N2 - 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 old, at intermediate risk for CHD, and not on statins) were randomized 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 (H-GRS) or average/low (L-GRS) GRS. Risk was disclosed by a genetic counselor followed by shared decision-making regarding statin therapy with a physician. We compared the primary endpoint of LDL-C levels at 6 months and assessed whether any differences were due 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 vs. 105.9±33.3 mg/dL; P=0.04). H-GRS participants had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not L-GRS participants (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the GRS group than in the CRS group (39% vs. 22%, P

AB - 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 old, at intermediate risk for CHD, and not on statins) were randomized 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 (H-GRS) or average/low (L-GRS) GRS. Risk was disclosed by a genetic counselor followed by shared decision-making regarding statin therapy with a physician. We compared the primary endpoint of LDL-C levels at 6 months and assessed whether any differences were due 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 vs. 105.9±33.3 mg/dL; P=0.04). H-GRS participants had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not L-GRS participants (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the GRS group than in the CRS group (39% vs. 22%, P

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