Hypoxic pulmonary hypertension attenuated by iron supplementation, worsened by iron depletion, according to analysis in Peru

Iron levels in the body appear to affect the severity of hypoxic pulmonary hypertension during prolonged periods, 2 trials show. The randomized, double-blind studies were carried out to determine whether iron supplementation or depletion would modify altitude-induced hypoxic pulmonary hypertension throughout several days and weeks. Doppler echocardiography was used to measure changes in pulmonary artery systolic pressure (PASP). During the first sea-level resident study, 22 healthy...

Iron levels in the body appear to affect the severity of hypoxic pulmonary hypertension during prolonged periods, 2 trials show.

The randomized, double-blind studies were carried out to determine whether iron supplementation or depletion would modify altitude-induced hypoxic pulmonary hypertension throughout several days and weeks. Doppler echocardiography was used to measure changes in pulmonary artery systolic pressure (PASP).

During the first sea-level resident study, 22 healthy volunteers who grew up at sea level ascended during a period of 8 hours to Cerro de Pasco, Peru, where the altitude is 4,340 m and average barometric pressure is approximately 450 mm Hg (equal to breathing approximately 12% oxygen at sea level). On the third day of this week at high altitude, they received infusions of Fe(III)-hydroxide sucrose or placebo intravenously.

The 1-month chronic mountain sickness protocol involved 11 patients who were long-term residents of Cerro de Pasco and had chronic mountain sickness and elevated baseline PASP of 37 mm Hg. They underwent staged isovolemic venesection during the first 4 days to remove 2 L of blood. Two weeks later, the patients were randomized to receive either Fe(III)-hydroxide sucrose or placebo infusions. On day 25 of the 1-month study, the patients were crossed over to the other study arm.

In the sea-level resident protocol, PASP significantly increased when the patients were exposed to high altitude at day 3 (from 24 mm Hg to 39 mm Hg; P<.001). However, iron infusion reversed much of this rise, so that PASP declined from 37 mm Hg to 31 mm Hg. Placebo infusion led to a change from 40 mm Hg to just 38 mm Hg (between-group difference, P=.01). The iron's effect was evident within 4 hours of infusion.

In the chronic mountain sickness study, iron deficiency from venesection led to an approximate 25% rise in PASP to 46 mm Hg (P=.003). The iron replacement infusion did not acutely oppose the increased pulmonary artery pressure associated with iron depletion, and no affect of iron replacement on PASP was observed during the crossover period.

"Our findings … suggest that careful adjustment of iron balance may have a place in the broader management of hypoxic pulmonary hypertensive disease," the researchers concluded. (Smith TG, et al. JAMA 2009;302:1444-1450.)