Abstract

Introduction: Iron deficiency affects 10% of adults aged 70 years or older and is associated with worse symptom burden and a higher risk of hospitalization in adults with heart failure (HF) with reduced ejection fraction (HFrEF) in mid-life. However, the relationships between iron deficiency and incident HF, HFrEF and HF with preserved EF (HFpEF) in late life remain incompletely understood. Hypothesis: Iron deficiency, as measured by lower plasma ferritin levels, is associated with an increased risk of incident HF, HFrEF, and HFpEF in older adults. Methods: We included 3,567 participants (mean age 75 years, 56% women and 14% Black) from the ongoing, ARIC study who had plasma ferritin measured by an aptamer assay (SomaLogic) and were free from prevalent HF and anemia (Hb <13 for men and <12 for women). The associations of log 2 -transformed plasma ferritin with adjudicated incident overall HF, HFrEF (LVEF < 50%) and HFpEF were estimated using Cox proportional hazards models. The associations of plasma ferritin with echocardiographic measures of cardiac size and function at Visit 5 were estimated with linear regression models. All models were adjusted for age, sex, race, smoking, body mass index, coronary heart disease, diabetes, hypertension, atrial fibrillation and eGFR. Results: Over a median 7 years of follow-up, 312 incident HF events occurred (140 HFrEF, 137 HFpEF, 51 unknown EF). Lower ferritin level was associated with a higher risk of overall HF and HFpEF, but not HFrEF ( Figure ). Lower ferritin levels associated with a higher E/e' ratio (standardized beta [95% CI]: 0.06 [0.03-0.08]; P<0.01). Plasma ferritin levels did not associate with LV mass index or measures of LV systolic function (ejection fraction, global longitudinal strain; all P > 0.05). Conclusion: Lower plasma ferritin levels associate with higher LV filling pressure and greater risk of incident HF, and in particular HFpEF, in late life. Iron deficiency may contribute to the pathophysiology of HF in late life.

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