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

AbstractBackgroundResearch 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%.ObjectivesThis 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).MethodsHbA1c 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.ResultsThe prevalence of the Hp2-2 genotype in HPFS was 39%. Compared with HbA1c