Hemoglobin A1c, Body Mass Index, and the Risk of Hypertension in Women

BACKGROUND: Although basic research has implicated abnormal glucose metabolism in the pathogenesis of hypertension (HTN), epidemiologic studies are limited. METHODS: We assessed whether baseline hemoglobin A(1c) (HbA(1c)) was prospectively associated with HTN in the Women's Health Study (WHS). We analyzed 19,858 women initially free of HTN, diabetes, and cardiovascular disease (CVD) with baseline blood samples. We considered quintiles and clinical cutpoints of HbA(1c) for the risk of HTN, defined as either a new physician diagnosis, the initiation of antihypertensive treatment, or systolic blood pressure (SBP) ≥140 or diastolic blood pressure (DBP) ≥90 mm Hg. RESULTS: During a median follow-up of 11.6 years, 9,408 (47.5%) women developed HTN. In models adjusted for traditional cardiovascular risk factors, the hazard ratios (HRs) from the lowest (<4.8%, referent) to the highest (≥5.2%) quintile of HbA(1c) were 1.0 (referent), 0.99, 1.06, 1.08, and 1.21 (P, linear trend <0.0001). However, additional adjustment for body mass index (BMI) eliminated the relation (extreme quintile comparison HR 1.04; P, linear trend 0.10). For clinical cutpoints, a similar pattern emerged although a positive association between HbA(1c) and HTN remained in the highest category. CONCLUSIONS: HbA(1c) in women without diabetes was associated with an increased risk of HTN in models controlling for the majority of traditional HTN and coronary risk factors, but this relation was no longer significant after adjustment for BMI. These findings underscore the need for additional studies to delineate the important inter-relationships between glycemia and adiposity with the risk of HTN in other study populations.