Hemoglobin, Frailty, and Long-term Cardiovascular Events in Community-Dwelling Older Men Aged ≥ 70 Years

Background: Anemia is associated with increased risk of all-cause mortality in older populations. However, the relationship between hemoglobin and major adverse cardiovascular events (MACE), and whether this is modulated by frailty, is unclear. Methods: CHAMP (Concord Health and Ageing in Men Project) is a prospective study of community-dwelling men aged >= 70 years. The relationship between hemoglobin and 7-year MACE was analysed by means of Cox regression. The Youden index was used to determine the optimal hemoglobin cutoff point in predicting MACE. Frailty was assessed with the use of the Fried criteria. Results: The cohort comprised 1604 men (mean +/- SD age 76.9 +/- 5.5 years). Decreasing hemoglobin was associated with increased comorbidity, frailty, and MACE (P < 0.001), with 140 g/L the optimal cutoff point for predicting MACE. Hemoglobin, age, and frailty independently predicted MACE (all P < 0.001). Each 10 g/L decrement in hemoglobin level was associated with increased risk of MACE (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.06-1.20; P < 0.001), all-cause mortality (HR 1.20, 95% CI 1.12-1.29; P < 0.001), cardiovascular mortality (HR 1.07, 95% CI 1.01-1.14; P = 0.025), myocardial infarction (HR 1.17, 95% CI 1.09-1.25; P < 0.001), and heart failure (HR 1.17, 95% CI 1.09-1.25; P < 0.001). When stratified into hemoglobin quintiles, men in the lowest 2 quintiles (Hb 133-140 g/L and < 132g/L, respectively) were at increased risk of MACE, cardiovascular mortality, myocardial infarction, and heart failure (all P < 0.05). This relationship for MACE was independent from frailty status, with the test for interaction between frailty and hemoglobin not reaching significance (P = 0.24). Conclusions: Low hemoglobin was associated with increased MACE in community-dwelling older men independently from frailty. A hemoglobin cutoff point of 140 g/L, a level that is above contemporary definitions of anemia, predicted long-term MACE.