Association of Hemoglobin Concentration and Its Change With Cardiovascular and All-Cause Mortality

Abstract

Background: Anemia is thought to increase mortality risks, but the effects of high hemoglobin concentration on survival are unclear. The effect of change in hemoglobin concentrations on survival in the general population is also unknown. This study aimed to examine the effect of hemoglobin concentrations and their changes on cardiovascular and all-cause mortality risks.

Methods and results: We retrospectively analyzed a cohort from the NHIS-HEALS (National Health Insurance Service-National Health Screening Cohort) database, including 170 078 men and 122 116 women without cardiovascular diseases, aged >40 years at baseline, with hemoglobin concentrations available for both first and second health examinations. We assessed 2 independent variables: "One-time" hemoglobin concentrations and changes in hemoglobin from first to second examination. Participants were followed up for a median of 8 years to determine mortality related to myocardial infarction, stroke, all cardiovascular diseases, and all causes. Hemoglobin concentrations showed a U- or J-shaped association with cardiovascular and all-cause mortality after adjusting for cardiovascular risk factors. When anemic men achieved normal hemoglobin concentrations, the all-cause mortality risk decreased, with an adjusted hazard ratio of 0.67 (95% confidence interval, 0.59-0.77), in comparison with those whose anemia persisted. Both increases and decreases of hemoglobin concentration outside the normal range elevated all-cause mortality risk (adjusted hazard ratio: 1.39 [95% confidence interval, 1.28-1.49] and 1.10 [95% confidence interval, 1.01-1.20], respectively), compared with persistent normal hemoglobin concentrations. The trend was similar in women but was less significant.

Conclusions: Low or high hemoglobin concentrations were associated with elevated cardiovascular and all-cause mortality. Reaching and maintaining hemoglobin concentrations within the normal range correlated with decreased all-cause mortality.

Keywords: anemia; hemoglobin; mortality; myocardial infarction; stroke.

Figure 1

Timeline of the study. CVD indicates cardiovascular disease; Hb, hemoglobin; MI, myocardial infarction.

Figure 2

Association between hemoglobin concentration and cardiovascular and all‐cause mortality by sex. HR was calculated by Cox proportional hazards regression analysis adjusted for age, socioeconomic status, physical activity, smoking status, alcohol use, body mass index, blood pressure, fasting serum glucose, total cholesterol, and Charlson comorbidity index (95% confidence interval). International Classification of Diseases, 10th Revision codes were used to identify and classify the outcomes: MI (I21–I24), total stroke (I60–I69), and all CVD (I10–I99). CVD indicates cardiovascular disease; HR indicates hazard ratio; MI, myocardial infarction.

Figure 3

Unadjusted cumulative hazard curves for 8‐year all‐cause mortality by change in hemoglobin concentration status and by sex. Cumulative hazard based on first health examination: (A) men with Hb <13 g/dL, (B) men with Hb 13 to 15.9 g/dL, (C) men with Hb ≥16 g/dL, (D) women with Hb <12 g/dL, (E) women with Hb ≥12 g/dL. Hb indicates hemoglobin.