The Association between Hemoglobin Concentrations and Cardiovascular Disease in Postmenopausal Women within the Women's Health Initiative

Abstract

INTRODUCTION: Cardiovascular disease (CVD) is a leading cause of death in the United States. It can lead to hospitalization, disability, mortality and decreased quality of life. Abnormal hemoglobin concentration (anemia or higher than normal level) has been proposed as a potential risk factor for CVD. However, it has not been tested in general postmenopausal women using large perspective study method. The overall objective of this dissertation is to examine the association between abnormal hemoglobin concentration, left ventricular hypertrophy (LVH), and cardiovascular outcomes in postmenopausal women. METHODS: This dissertation unitized data from the Women's Health Initiative (WHI) cohort. Hemoglobin concentrations were classified into several categories: normal (12g/dl ≤ hemoglobin ≤ 15g/dl), mild anemia (hemoglobin < 12g/dl), moderate anemia (hemoglobin < 11g/dl), severe anemia (hemoglobin < 10.5g/dl), and extremely high hemoglobin (EHH) (hemoglobin > 15g/dl). Three associations were assessed. Hemoglobin concentration and subsequent cardiovascular events were tested in the WHI participants without prior CVD (n=123,465). The association between hemoglobin concentration and cardiovascular death was tested in the WHI participants with prior CVD (n=26,929). The last study, testing the association between hemoglobin concentration and LVH, were assessed cross-sectionally in the WHI clinical trials which had electrocardiographic (ECG) data (n=57,551). RESULTS: In women without prior CVD, both anemia and EHH was associated with an increased risk of cardiovascular events. The association varied by age groups, and EHH associated cardiovascular risk decreased with age. In women with prior CVD, risk of cardiovascular death significantly increased by 48%, 90% and 32% in mild anemia, moderate/severe anemia, and EHH group respectively compared to normal group. In the WHI participants who had ECG data, odds ratios of LVH were 1.13 (95% CI: 0.90-1.41), 1.35 (95% CI: 0.76-2.40), and 1.32 (95% CI: 0.76-2.40) for mild anemia, moderate/severe anemia, and EHH group respectively compared to normal group. CONCLUSION: These studies constantly demonstrated a U-shaped association between hemoglobin concentration and cardiovascular risk in the postmenopausal women. It suggests that the association of hemoglobin concentration and incidence of CVD was modified by age. Additional research is needed to determine whether there is a cause-and-effect relationship between hemoglobin concentration and LVH.