The Risk of Coronary Heart Disease Associated With Glycosylated Hemoglobin of 6.5% or Greater Is Pronounced in the Haptoglobin 2-2 Genotype

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:66

Article

Cahill, Leah E.¹  Jensen, Majken K.^1,2,3  Chiuve, Stephanie E.^1,3,4,5  Shalom, Hadar⁶  Pai, Jennifer K.^2,3,5  Flint, Alan J.^1,5  Mukamal, Kenneth J.⁷  Rexrode, Kathryn M.^3,4  Levy, Andrew P.⁶  Rimm, Eric B.^1,2,3,5 

[1] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA

[5] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[6] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel

[7] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA

关键词: acute myocardial infarction;    coronary disease;    epidemiology;    genetic association;    glycoproteins;   

DOI  :  10.1016/j.jacc.2015.07.076

来源: Elsevier

【 摘 要 】

BACKGROUND Research targeting glycosylated hemoglobin A1c (HbA(1c)) to <6.5% to prevent coronary heart disease (CHD) events has conflicting results. We previously observed the haptoglobin (Hp) Hp2-2 genotype is associated with a similar to 10-fold increased CHD risk among individuals with HbA(1c) >= 6.5%, and thus might be useful in identifying those at high risk of CHD who would benefit from maintaining HbA(1c) <6.5%. OBJECTIVES This study sought to model whether HbA(1c) >= 6.5% in the Hp2-2 genotype is associated with CHD in a prospective case-control study nested within the Health Professionals Follow-Up Study (HPFS). METHODS HbA(1c) concentration and Hp genotype were determined for 695 incident cases of CHD from 1994 to 2010 and matched control participants. Logistic regression models calculated relative risk (RR) and 95% CI, for the first and second halves of follow-up, adjusting for confounding variables. A dataset from the Nurses' Health Study served as a replication cohort. RESULTS The prevalence of the Hp2-2 genotype in HPFS was 39%. Compared with HbA(1c) <6.5%, the RR of CHD for HbA(1c) >= 6.5% for the Hp2-2 genotype over full follow-up was 3.07 (95% CI: 1.37 to 6.86) to 3.88 (95% CI: 1.31 to 11.52) during the first half of follow-up and 2.16 (95% CI: 0.61 to 7.61) in the second half. The corresponding RRs for the Hp1-1 + Hp2-1 genotypes were: full follow-up, 2.19 (95% CI: 1.14 to 4.24); first half, 1.60 (95% CI: 0.73 to 3.53); and second half, 4.72 (95% CI: 1.26 to 17.65). CONCLUSIONS In 2 independent cohorts, the risk of CHD associated with HbA(1c) >= 6.5% is pronounced in the Hp2-2 genotype, particularly in early cases. The Hp2-2 genotype may identify individuals at greatest CHD risk from hyperglycemia. (C) 2015 by the American College of Cardiology Foundation.

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