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J Am Coll Cardiol. 2015 Oct 20;66(16):1791-1799. doi: 10.1016/j.jacc.2015.07.076.

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

Author information

1
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. Electronic address: lcahill@hsph.harvard.edu.
2
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
3
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
4
Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
5
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
6
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
7
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
8
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
9
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.

Abstract

BACKGROUND:

Research targeting glycosylated hemoglobin A1c (HbA1c) 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 HbA1c ≥6.5%, and thus might be useful in identifying those at high risk of CHD who would benefit from maintaining HbA1c <6.5%.

OBJECTIVES:

This study sought to model whether HbA1c ≥ 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:

HbA1c 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 HbA1c <6.5%, the RR of CHD for HbA1c ≥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 HbA1c ≥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.

KEYWORDS:

acute myocardial infarction; coronary disease; epidemiology; genetic association; glycoproteins

PMID:
26483103
PMCID:
PMC4616252
DOI:
10.1016/j.jacc.2015.07.076
[Indexed for MEDLINE]
Free PMC Article

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