Sex-specific Associations Between Serum Hemoglobin Levels and the Risk of Cause-specific Death in Korea Using the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS)

Objectives: The purpose of this study was to determine the associations between blood hemoglobin (Hgb) levels and the risk of death by specific causes. Methods: Using the National Health Insurance Services-National Health Screening Cohort (n=487 643), we classified serum Hgb levels into 6 sex-specific groups. Cox regression analysis was used to analyze the associations between Hgb levels and the risk of cause-specific death. Results: Hgb levels in male population showed a U-shaped, J-shaped, or inverse J-shaped association with the risk of death from ischemic heart disease, acute myocardial infarction, liver cancer, cirrhosis and chronic obstructive pulmonary disease (COPD) (all non-linear p<0.05; hazard ratio [HR]; 95% confidence interval [CI]) for the lowest and the highest Hgb levels for the risk of each cause of death in male population: HR, 1.14; 95% CI, 0.98 to 1.34; HR, 2.87; 95% CI, 1.48 to 5.57; HR, 1.16; 95% CI, 0.96 to 1.40; HR, 3.05; 95% CI, 1.44 to 6.48; HR, 1.36; 95% CI, 1.18 to 1.56; HR, 2.11; 95% CI, 1.05 to 4.26; HR, 3.64; 95% CI, 2.49 to 5.33; HR, 5.97; 95% CI, 1.44 to 24.82; HR, 1.62; 95% CI, 1.14 to 2.30; HR, 3.84; 95% CI, 1.22 to 12.13, respectively), while in female population, high Hgb levels were associated with a lower risk of death from hypertension and a higher risk of death from COPD (overall p<0.05; HR, 1.86; 95% CI, 1.29 to 2.67 for the lowest Hgb levels for hypertension; overall p<0.01, HR, 6.60; 95% CI, 2.37 to 18.14 for the highest Hgb levels for COPD). For the risk of lung cancer death by Hgb levels, a linear negative association was found in male population (overall p<0.01; the lowest Hgb levels, HR, 1.17; 95% CI, 1.05 to 1.33) but an inverse J-shaped association was found in female population (non-linear p=0.01; HR, 1.25; 95% CI, 0.96 to 1.63; HR, 2.58; 95% CI, 1.21 to 5.50). Conclusions: Both low and high Hgb levels were associated with an increased risk of death from various causes, and some diseases showed different patterns according to sex.