Los Angeles—Research finding an association with iron deficiency and development of heart failure (HF) questions whether routine iron replacement should be considered.

The study published in ESC Heart Failure looked at the relationship of iron status with incident HF in community-dwelling older adults without regard to their kidney function.

“Among persons with prevalent heart failure (HF), iron deficiency has been linked to HF admissions, and intravenous iron replacement improves HF outcomes,” the University of California, Los Angeles–led researchers noted. “Recent studies in persons with chronic kidney disease (CKD) demonstrate that iron deficiency is associated with incident HF.”

For the case-cohort study, the investigative team focused on 1,006 Cardiovascular Health Study participants (785 from the random subcohort [including 193 HF cases] and 221 additional HF cases [N = 414 total HF cases]). Participants were aged 65 years and older without HF, although 41% had CKD.

Consistent with prior studies, participants were categorized based on quartiles of transferrin saturation and ferritin as:

• Iron replete (27.3%)
• Functional iron deficiency (7.7%)
• Iron deficiency (11.8%)
• Mixed iron deficiency (5.6%)
• High iron (9.3%)
• Nonclassified (38.1%).

“Compared to older persons who were iron replete, those with iron deficiency were at higher risk of incident HF (HR [hazard ratio] 1.47; 1.02-2.11) in models adjusting for demographics, HF risk factors, and estimated glomerular filtration rate,” the authors wrote. “Other iron categories did not associate with incident HF. The relationship of iron deficiency with incident HF did not differ by CKD status (interaction P value 0.2).”

The study concluded that, among community-dwelling elders, iron deficiency is independently associated with incident HF, an association that was similar irrespective of CKD status. “Our findings support conduct of clinical trials of iron replacement for prevention of HF in older adults with iron deficiency,” the researchers added.

Other recent studies have raised concerns about new onset chronic kidney disease with the use of oral iron replacement. This trial with U.S. veterans was published in the European Journal of Haematology and involved 33,894 incident new users of oral iron replacement and a comparable group of 112,780 patients who did not receive any iron replacement during 2004-2018.

The study reported that 13% of patients experienced incident estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and 11% experienced new-onset urine albumin creatinine ratio of ≥30 mg/g.

“Oral iron replacement was associated with significantly higher risk of incident eGFR <60 mL/min/1.73 m2 (subhazard ratio, 95% confidence interval [CI]: 1.3 [1.22-1.38], P <.001) and incident albuminuria (subhazard ratio, 95% CI: 1.14 [1.07-1.22], P <.001),” the researchers wrote, adding, “Oral iron replacement is associated with higher risk of new onset CKD. The long-term kidney safety of oral iron replacement should be tested in clinical trials.”

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