Iron is essential for the homeostasis of the human body. It plays a central role in oxygen transport and utilization as well as in mitochondrial function. However, it is well known that iron deficiency is quite common in general population. Historically, iron status has been assessed by measuring ferritin serum levels, and patients with low ferritin serum levels have been diagnosed with absolute iron deficiency. However, ferritin alone might not suffice to provide an accurate and reliable assessment of iron status, as it solely reflects stored iron. Transferrin saturation (TSAT) should be additionally measured to account for utilized iron. Measurement of both markers provides a more accurate description of iron status and can identify patients with a functional iron deficiency. Recently, several cardiovascular studies have indicated an association of absolute and functional iron deficiency with morbidity and mortality in patients with cardiovascular diseases (CVDs) such as coronary heart disease (CHD), acute myocardial infarction, and heart failure. However, their relevance for the general population is unknown.
In October 2021, a new analysis aiming was to assess the association between iron deficiency and incident CV disease and mortality in the general population was published in ESC Heart Failure. It was based on 12 146 individuals from three cohort studies (KORA, Northern Sweden, and Tromsø) with available baseline ferritin and TSAT data. For the current analysis, absolute iron deficiency was defined as ferritin < 100 μg/L and severe absolute iron deficiency as ferritin < 30 μg/L. Functional iron deficiency was defined as ferritin < 100 μg/L or ferritin 100–299 μg/L and TSAT < 20%. Adjustments were performed for age (time scale), sex (strata), smoking, total cholesterol, SBP, diabetes, BMI, hsCRP, and study centre (strata).
The median age of the study population was 59 (45–68) years; 45.2% were male. Among the 12 164 individuals, 7296 (60.0%) had ferritin < 100 μg/L and fulfilled the criteria of absolute iron deficiency, whereas 1989 (16.4%) had ferritin < 30 μg/L and fulfilled the criteria of severe absolute iron deficiency; and 7825 (64.3%) individuals had ferritin between 100 and 299 μg/L and TSAT < 20% and fulfilled the criteria of functional iron deficiency. During a median follow-up of 13.3 years, 2212 individuals (18.2%) died. Of these, a total of 573 individuals (4.7%) died from a cardiovascular cause. A total of 1033 individuals (8.5%) were diagnosed with incident CHD during the follow-up. Incident stroke was diagnosed in 766 (6.3%) individuals.
After adjustment for multiple confounders, absolute iron deficiency was not associated with all-cause mortality [hazard ratio (HR) 1.08, 95% CI 0.98–1.19, P = 0.12] or with cardiovascular mortality (HR 1.22, 95% CI 1.00–1.48, P = 0.05). Absolute iron deficiency was associated with incident CHD (HR 1.20, 95% CI 1.04–1.39, P = 0.01), but not with incident stroke (HR 1.11, 95% CI 0.94–1.31, P = 0.22). Severe absolute iron deficiency was significantly associated with all-cause mortality (HR 1.28, 95% CI 1.12–1.46, P < 0.01) but was not associated with cardiovascular mortality (HR 1.01, 95% CI 0.76–1.344, P = 0.95) and also not with incident CHD (HR 1.22, 95% CI 1.00–1.50, P = 0.05) or incident stroke (HR 1.10, 95% CI 0.87–1.40, P = 0.42).
Functional iron deficiency was significantly associated with all-cause mortality (HR 1.12, 95% CI 1.01–1.24, P = 0.03), with cardiovascular mortality (HR 1.26, 95% CI 1.03–1.54, P = 0.03), with incident CHD (HR 1.24, 95% CI 1.07–1.43, P < 0.01), but not with incident stroke (HR 1.15, 95% CI 0.97–1.36, P = 0.12).
Overall, 5.4% of all deaths, 11.7% of all CV deaths, and 10.7% of CHD were attributable to FID.
Reference: https://onlinelibrary.wiley.com/doi/10.1002/ehf2.13589
