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Plasma Ferritin Levels and Incident HF in Older Adults
Quick Takes
- Older adults without HF or anemia with lower plasma ferritin were associated with a higher risk for incident HF, HFpEF, and higher measures of LV filling pressure.
- Further studies are needed to evaluate predictive iron studies other than ferritin as well as the effect of treatment of iron deficiency on incident HF.
Study Questions:
What is the association between plasma ferritin in older adults and incident heart failure (HF), HF phenotypes, and cardiac structure and function measures?
Methods:
This was a report from the ARIC (Atherosclerosis Risk In Communities) study, an ongoing longitudinal cohort study that enrolled 15,792 community-dwelling adults between the ages of 45–64 years from 1987–1989 at four U.S. sites. This analysis included 3,472 patients with no history of HF or anemia with available plasma ferritin and covariate measurements from ARIC visit 5 (2011–2013). Associations between plasma ferritin level, incident HF, HF phenotype (HF with preserved ejection fraction [HFpEF], HF with reduced ejection fraction [HFrEF], or unknown), measures of cardiac structure and function, and the composite of incident HF and cardiovascular (CV) death were assessed. Primary and secondary exposures were plasma ferritin light chain and complex of ferritin heavy and light chains. Incident HF was defined as the first occurrence of a hospitalization for HF or HF death after visit 5. Cardiac structure and function outcomes were assessed using echocardiographic methods at ARIC visit 5.
Results:
The median age was 74 years (interquartile range, 71-78), 56% were women, and 14% reported Black race. Lower ferritin levels were more likely to be found in women, reported White race, lower body mass index, higher systolic blood pressure, reported aspirin use, and in those less likely to report current alcohol use. Lower plasma ferritin levels were associated with lower red blood cell indexes.
A total of 293 incident HF events occurred over a follow-up period of 7.2 years with an incidence rate of 12.6 per 1,000 person-years (95% confidence interval [CI], 11.3-14.2). Of the incident HF events, 131 were HFrEF, 131 HFpEF, and 31 with unknown left ventricular ejection fraction (LVEF). A 50% lower plasma ferritin level was associated with a higher risk for incident HF overall (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.08-1.34) and a higher risk for incident HFpEF (HR, 1.28; 95% CI, 1.09-1.50; p = 0.002) both after adjustment for demographics and clinical risk factors. This same association was not found with HFrEF (HR, 1.16; 95% CI, 0.99-1.36; p = 0.07). These associations were not modified after analysis by various models including demographics, clinical risk factors, or potential confounders. Lower ferritin levels were associated with worse diastolic function by multiple measures and higher LV filling pressure but were not associated with measures of LV size or mass or measures of LV systolic function. A nonlinear relationship between plasma ferritin level and HF risk was not observed. Ferritin levels were not associated with risk for CV death, all-cause death, or the composite of incident HF and CV death.
Conclusions:
In older adults without a history of HF or anemia, this observational study showed an association between lower plasma ferritin levels and a higher risk for incident HF, incident HFpEF, and LV diastolic dysfunction.
Perspective:
The prevalence of iron deficiency with or without anemia has been a growing area of interest for prediction of incident CV disease. This large observational study supports that low serum ferritin is associated with incident HF after adjustment for multiple risk factors and other confounders. The type of HF most frequently observed was HFpEF, although the absence of a significant association with HFrEF may have been due to limited power. The incidence of HF increases with increasing age and this study provides insight in older adults (mean age, 75 years) compared to an earlier ARIC study in younger adults (mean age, 53 years).
There has been growing discussion in the HF population as to which iron studies are the most predictive of adverse clinical outcomes, with consideration for utilizing serum iron and transferrin saturation over serum ferritin levels. This study used a research assay to assess ferritin levels instead of the more common clinically validated assays, which limits the ability to assess specific ferritin cutoffs and generalizability. Further study is needed to determine if other markers of iron deficiency confer similar associations with incident HF and the effects of treating iron deficiency in this cohort.
Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Acute Heart Failure
Keywords: Ferritins, Heart Failure
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