Higher hemoglobin levels within reference interval are associated with elevated cardiometabolic traits in a birth-cohort of 16-year-old adolescents

Hemoglobin (Hb) levels are commonly measured to assess health and oxygen transport. While levels outside the reference interval indicate anemia or polycythemia, higher Hb levels within the referenced interval have been linked to adverse cardiometabolic traits in adults. As cardiometabolic traits are exacerbated by aging, associations in older subjects are susceptible to confounding effects such as co-morbidities, medications, and lifestyle factors e.g., smoking. Our aims were to: 1) Cross-sectionally establish whether Hb levels within the Finnish reference interval are associated with anthropometric and cardiometabolic traits including >100 systemic metabolites in 16-year-old adolescents of the Northern Finland Birth Cohort 1986 (n = 5,795), 2) Evaluate the effects of sex and smoking on these associations by restriction, and 3) Establish whether Hb levels at age of 16 are associated with metabolic traits at age of 33. Regression models were used to further account for confounding factors. Hb levels were associated positively with body mass index and other anthropometric measures, leucocyte count, glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, small-to-extremely-large VLDL particle, alanine, creatinine and testosterone levels, and blood pressure and heart rate at age of 16. Associations were generally stronger in males, except of those for leucocyte count and glucose and insulin levels which were stronger in females. Adjusting for smoking weakened the associations. Longitudinally, Hb levels at age of 16 associated positively with anthropometric measures at age of 33. These data suggest that higher Hb levels, even within the reference interval, may reflect early cardiometabolic risk, with sex and smoking influencing the strength of associations.