Abstract
Background
Functional iron deficiency (FID) has been established as a risk factor in patients with cardiovascular diseases (CVD). As opposed to absolute iron deficiency, it reflects stored iron as well as utilized iron and allows for a more accurate evaluation of individual iron status. However, evidence is scant on the relevance of FID to the incidence of CVD in the general population.
Aim
This study aimed to evaluate the association of FID with incident cardiovascular diseases and mortality endpoints in a large population-based cohort.
Methods
FID was defined as either ferritin below 100 μg/L or ferritin between 100 and 299 μg/L and transferrin saturation below 20%. Only individuals free of CVD at baseline from three population-based European cohorts were included. Multivariable-adjusted sex- and cohort-stratified Cox regression analyses were performed to evaluate the association of functional iron deficiency with incident cardiovascular diseases (coronary heart disease, cerebral infarction, heart failure and atrial fibrillation) as well as with all-cause and cardiovascular mortality. Adjustments were performed for sex (as strata), age (as time scale), smoking, total cholesterol, systolic blood pressure, diabetes, body mass index and high-sensitive C-reactive protein.
Results
In total, N=12146 individuals were included in the analysis with a median age of 59.0 years (25thpercentile 45.0, 75thpercentile 68.0), and 45.2% men. Incidence of FID was 64.3%. Median follow-up times were 12.3 to 21.8 years, with an all-cause mortality rate of 18.2% and a cardiovascular mortality rate of 6.2%. Incident coronary heart disease, cerebral infarction, heart failure and atrial fibrillation were observed in 8.7%, 6.5%, 5.9% and 11.7%, respectively.
FID was significantly associated with all-cause mortality (hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.01–1.24, p=0.034), cardiovascular death (HR 1.26, 95% CI 1.03–1.54, p=0.027) and incident coronary heart disease (HR 1.23, 95% CI 1.06–1.43, p<0.01). There was no significant association with the other tested endpoints.
Conclusion
In our analysis of population-based cohorts, FID showed a significant positive association with all-cause as well as cardiovascular mortality and incident coronary heart disease. Further research is needed to validate the role of FID as a cardiovascular risk factor in the general population and to evaluate the impact of iron supplementation on gender and outcome.
Lipoprotein-Associated Phospholipase A2 Is an Independent Predictor of Incident Coronary Heart Disease in an Apparently Healthy Older Population
