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

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• 作者：Leah E. Cahill ; PhD^&lowast ; ; ^{lcahill@hsph.harvard.edu" class="auth_mail" title="E-mail the corresponding author} ; Majken K. Jensen ; PhD^&lowast ; ; ^&dagger ; ; Stephanie E. Chiuve ; ScD^&lowast ; ; ^&Dagger ; ; ^§ ; ; Hadar Shalom ; MSc^鈥?/sup> ; Jennifer K. Pai ; ScD^&dagger ; ; ^§ ; ; Alan J. Flint ; MD ; DRPH^&lowast ; ; ^§ ; ; Kenneth J. Mukamal ; MD ; MPH^¶ ; ; Kathryn M. Rexrode ; MD ; MPH^&Dagger ; ; Andrew P. Levy ; MD ; PhD^鈥?/sup> ; Eric B. Rimm ; ScD^&lowast ; ; ^&dagger ; ; ^§ ;
• 关键词：acute myocardial infarction ; coronary disease ; epidemiology ; genetic association ; glycoproteins
• 刊名：Journal of the American College of Cardiology
• 出版年：2015
• 出版时间：20 October 2015
• 年：2015
• 卷：66
• 期：16
• 页码：1791-1799
• 全文大小：1165 K

文摘

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 ∼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.