Functional Iron Deficiency Linked to Increased Risk of Coronary Heart Disease, Cardiovascular Mortality

Benedikt Schrage, MD

Results from an observational analysis of 3 European-based cohorts provide evidence suggesting iron deficiency in middle age was linked to increased risk of poor cardiovascular health later in life.

Designed with the intent of assessing the risks posed by iron deficiency in the general population, results of the study indicate patients with functional iron deficiency (FID) had a 24% greater risk of coronary heart disease, a 26% greater risk of cardiovascular mortality, and a 12% greater risk of all-cause mortality.

“This was an observational study and we cannot conclude that iron deficiency causes heart disease,” said lead investigator Benedikt Schrage, MD, of the University Heart and Vasculature Centre Hamburg, Germany, in a statement. “However, evidence is growing that there is a link and these findings provide the basis for further research to confirm the results.”

As data related to the effects of iron deficiency continue to grow, Schrage and a team of colleagues form multiple institutions in Europe sought to examine associations between absolute iron deficiency (AID)/FID with incident cardiovascular disease and mortality among the general population. To do so, the current study was designed as an observational analysis of data from within the KORA, Northern Sweden, and Tromsø cohort studies.

From this trio of study cohorts, investigators identified 12,164 individuals for inclusion in the current study. This cohort had a median age of 59 (IQR, 45-68) years, a median follow-up time of 13.3 years, and 45.2% were male. Of the 12,164 identified for inclusion 7296 (60%) had AID, 1989 (16.4%) had severe AID, 7825 had FID, and 4868 had no absolute iron deficiency. Of note, AID was defined as ferritin below 100 μg/L and severe AID as ferritin below 30 μg/L. FID was defined as ferritin above 100 μg/L or ferritin 100–299 μg/L and TSAT below 20%. Investigators planned to assess associations between iron deficiency and incident coronary heart disease, incident stroke, cardiovascular mortality, and all-cause mortality using Cox regression models.

During the course of the follow-up period, 2212 individuals died, including 573 from cardiovascular causes. A total of 1033 individuals were diagnosed with incident coronary heart disease and 766 were diagnosed with incident stroke during the follow-up.

In adjusted analysis, results suggested AID was not associated with all-cause mortality (HR, 1.08 [95% CI, 0.98-1.19]; P=.12) cardiovascular mortality (HR, 1.22 [95% CI, 1.00-1.48]; P=.05), or incident stroke (HR, 1.11 [95% CI, 0.94-1.31]; P=.22), but was associated with increased risk of incident coronary heart disease (HR, 1.20 [95% CI, 1.04=1.39]; P=.01). Further analysis suggested severe AID was associated with increased risk of all-cause mortality (HR, 1.28 [95% CI, 1.12-1.46]; P <.01), but not cardiovascular mortality (HR, 1.01 [95% CI, 0.76-1.344]; P=.95), incident coronary heart disease (HR, 1.22 [95% CI, 1.00-1.50]; P=.05), or incident stroke (HR, 1.10 [95% CI, 0.87-1.40]; P=.42).

When assessing associations with FID, results indicated FID was significantly associated with all-cause mortality (HR, 1.12 [95% CI 1.01–1.24]; P=.03),cardiovascular mortality (HR, 1.26 [95% CI 1.03–1.54] P=.03), and incident coronary heart disease (HR, 1.24 [95% CI 1.07–1.43] P <.01), but not incident stroke (HR, 1.15 [95% CI, 0.97–1.36]; P=.12).

“This analysis suggests that if iron deficiency had been absent at baseline, about 5% of deaths, 12% of cardiovascular deaths, and 11% of new coronary heart disease diagnoses would not have occurred in the following decade,” Schrage added. “The study showed that iron deficiency was highly prevalent in this middle-aged population, with nearly two-thirds having functional iron deficiency. These individuals were more likely to develop heart disease and were also more likely to die during the next 13 years.”

This study, “Association of iron deficiency with incident cardiovascular diseases and mortality in the general population,” was published in ESC Heart Failure.