Pulmonary hypertension not associated with iron deficiency, low iron levels

Neither iron deficiency nor low iron levels seem to be associated with pulmonary hypertension (PH), according to a recent analysis of the Jackson Heart Study, which was published in the December 14 issue of PLOS ONE.

“Iron deficiency has been reported to be present in up to 40-60% of patients with idiopathic pulmonary arterial hypertension, which is much higher than the prevalence of iron deficiency in the general population.  It is also commonly present in other clinical conditions that are associated with pulmonary hypertension, such as heart failure,” lead author Matthew Jankowich, MD, told MDLinx.

 “We were interested to see if the association between iron deficiency and idiopathic pulmonary arterial hypertension that has been reported in prior cohorts was also present in study participants from a community-based research study with evidence of elevated pulmonary artery pressures (which would likely be mostly related to non-idiopathic PH from heart disease, lung disease, etc.),” said Dr. Jankowich, who is assistant professor of medicine, Alpert Medical School of Brown University, Providence, RI, and staff physician, Providence VA Medical Center.

“Since iron deficiency is a relatively common problem, if an association with elevated pulmonary artery pressures were seen in this broader patient population, it would merit further investigation to see if iron deficiency was a cause of or contributor to pulmonary hypertension.  Since PH and iron deficiency both tend to be more common in women, this was also a reason to investigate the association, as it might explain some of this gender imbalance in predisposition to PH,” he added.

For this cross-sectional analysis, Dr. Jankowich and colleagues assessed iron deficiency (exposure) and PH (pulmonary artery systolic pressure > 40 mmHg on echocardiogram [outcome]) in 2,800 subjects enrolled in the Jackson Heart Study, a longitudinal, prospective, observational study of heart disease in African-Americans from Jackson, MS.

They defined iron deficiency as a serum ferritin level < 15 ng/mL for women and < 30 ng/mL for men. Using Poisson regression modeling, they calculated the crude prevalence ratios (PRs) for PH in iron deficient groups versus non-iron deficient groups. In addition, they assessed the prevalence of PH by sex-specific quartiles of ferritin (women ≤ 47 ng/mL; > 47 ng/mL to 95 ng/mL; > 95 ng/mL to 171 ng/mL; > 171 ng/mL; men ≤ 110 ng/mL; > 110 ng/mL to 182 ng/mL; > 182 ng/mL to 294 ng/mL; > 294 ng/mL), with the lowest quartile being the referent.

Patients had a median pulmonary artery systolic pressure of 27 mmHg, 5.2% (n=147) had PH, and 5.0% (n=140) had iron deficiency. Only 4 of the 147 patients with PH were also iron deficient. In iron-deficient patients compared to non-iron deficient, crude PH PR was 0.5 (95% CI: 0.2-1.4).

Upon analysis according to quartiles of ferritin adjusted for age and sex, Dr. Jankowich and colleagues found no evidence of an association with PH in quartile 2 (PR 1.1, 95% CI 0.7–1.6), 3 (PR 0.8, 95% CI: 0.5–1.3), or quartile 4 (PR 0.8, 95% CI: 0.5–1.2) compared to quartile 1, which was the referent group (PR 1). They saw similar results upon further analyses of the relationship between PH and ferritin as a log-transformed continuous variable or by quartiles of serum iron.

According to Dr. Jankowich: “Our findings of no association between iron deficiency and pulmonary hypertension in this broader patient population were something of a surprise, given how common the association seems to be in the idiopathic PAH population.  However, animal studies looking at the relationship between iron depletion or supplementation and pulmonary hypertension have shown conflicting results, and small studies in humans exposed to hypoxia suggest that iron is very important in regulating the pulmonary vascular response to hypoxia, but its role in non-hypoxic conditions is less clear.”

For clinicians treating patients with PH, the message is clear, according to Dr. Jankowich.

“Outside of the patient population with idiopathic or heritable PAH, we probably don't need to worry that our patients with iron deficiency are likely to have an increased risk of having pulmonary hypertension.  Iron deficiency should be investigated and treated, but we probably don't need to do extraneous tests like echocardiograms in patients with iron deficiency looking for pulmonary hypertension,” he concluded.

Co-author Gaurav Choudhary, MD, receives support from the National Heart, Lung, and Blood Institute Grant (1R01HL128661). The Jackson Heart Study is supported and conducted in collaboration with Jackson State University (HHSN268201300049C and HHSN268201300050C), Tougaloo College (HHSN268201300048C), and the University of Mississippi Medical Center (HHSN268201300046C and HHSN268201300047C) contracts from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute for Minority Health and Health Disparities (NIMHD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.