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Observational study find link between iron deficiency in middle age and coronary heart disease

Investigators Dr Benedikt Schrage (University Heart and Vasculature Centre Hamburg, Hamburg, Germany) and colleagues report in ESC Heart Failure that not only is iron deficiency highly prevalent in people who are middle-aged but also that individuals with iron deficiency are more likely to develop heart disease over the course of a decade.

According to an ESC press release, previous studies have shown that in patients with cardiovascular diseases (such as heart failure), iron deficiency is linked to worse outcomes — including hospitalisations and death. The aim of the new study was to examine whether the association between iron deficiency and outcomes is also seen in the general population.

Schrage et al reviewed data for 12,164 people from three European population-based cohorts. The median age was 59 years and 55% were women. During the baseline study visit, cardiovascular risk factors and comorbidities such as smoking, obesity, diabetes and cholesterol were assessed via a thorough clinical assessment including blood samples. Participants were classified as iron deficient or not according to two definitions: 1) absolute iron deficiency, which only includes stored iron (ferritin); and 2) functional iron deficiency, which includes iron in storage (ferritin) and iron in circulation for use by the body (transferrin).

Participants were followed up for incident coronary heart disease and stroke, death due to cardiovascular disease, and all-cause death. The investigators analysed the association between iron deficiency and incident coronary heart disease, stroke, cardiovascular mortality, and all-cause mortality after adjustments for age, sex, smoking, cholesterol, blood pressure, diabetes, body mass index, and inflammation. Participants with a history of coronary heart disease or stroke at baseline were excluded from the incident disease analyses.

At baseline, 60% of participants had absolute iron deficiency and 64% had functional iron deficiency. During a median follow-up of 13.3 years there were 2,212 (18.2%) deaths. Of these, a total of 573 individuals (4.7%) died from a cardiovascular cause. Incidence coronary heart disease and stroke were diagnosed in 1,033 (8.5%) and 766 (6.3%) participants, respectively.

Functional iron deficiency was associated with a 24% higher risk of coronary heart disease, 26% raised risk of cardiovascular mortality, and 12% increased risk of all-cause mortality compared with no functional iron deficiency. Absolute iron deficiency was associated with a 20% raised risk of coronary heart disease compared with no absolute iron deficiency but was not linked with mortality. There were no associations between iron status and incident stroke.

The researchers calculated the population attributable fraction, which estimates the proportion of events in 10 years that would have been avoided if all individuals had the risk of those without iron deficiency at baseline. The models were adjusted for age, sex, smoking, cholesterol, blood pressure, diabetes, body mass index, and inflammation. Within a 10-year period, 5.4% of all deaths, 11.7% of cardiovascular deaths, and 10.7% of new coronary heart disease diagnoses were attributable to functional iron deficiency. 

Dr Schrage comments: “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. 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.”

He added: “If the relationships are confirmed, the next step would be a randomised trial investigating the effect of treating iron deficiency in the general population.”

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