Anaemia, iron status, and gender predict the outcome in patients with chronic heart failure

Abstract

Aims: Anaemia and iron deficiency (ID) are frequently found in patients with chronic heart failure (CHF) and associated with adverse outcome. However, it is unclear whether absolute [transferrin saturation (TSAT) <20%, ferritin <100 μg/L] or inflammation-driven functional ID (TSAT <20%, ferritin >100 μg/L) with and without anaemia had similar or different consequences for such patients.

Methods and results: Within this retrospective cohort study, 2223 patients (1601 men and 622 women) with CHF, referred to our department, between 2000 and 2018, were followed for a median time of 84 months. Anaemia was found in 393 patients and was an independent predictor for an adverse outcome [HR 2.164 (95% CI 1.865-2.512), P < 0.001]. In 674 patients with available parameters of iron metabolism, ID was present in 228 patients and was associated with an unfavourable outcome [HR 1.499 (95% CI 1.158-1.940), P = 0.002]. ID was best predicting an adverse outcome in men ≤59 years, with heart failure with reduced ejection fraction, preserved kidney function, no inflammation, and a body mass index (BMI) ≥25.5 kg/m² . Functional ID in women and absolute ID in men were associated with poor prognosis. Of note, TSAT <20% but not low ferritin levels were predictive for an adverse outcome. Anaemic patients with high ferritin levels, advanced inflammation, older age, low BMI, male gender, and reduced glomerular filtration rate had the worst prognosis.

Conclusions: Anaemia and low tissue iron availability as reflected by TSAT <20% are negative predictors of outcome in patients with CHF. Systemic inflammation, renal function, BMI, age, and gender are important contributors for the clinical course.

Keywords: Anaemia; Gender; Heart failure; Iron deficiency; Outcome.

Figure 1

Kaplan–Meier plots of patients concerning anaemia, absolute/functional ID, and combined anaemia/ID classification. The number of remaining patients after 20, 40, 60, 80, 100, and 120 months is depicted below each figure. (A) Event‐free survival of patients with (n = 393, yellow) or without (n = 1830, blue) anaemia: the cumulative event rate within 10 years was 62.3% in anaemic and 37.2% in non‐anaemic patients (log‐rank test P < 0.001). (B) Patients with no ID and anaemia (n = 60, yellow) had the highest event rate after 10 years (87.3%). Also, patients with ID and anaemia (n = 75, orange) had a higher event rate (63.0%) compared with patients with no ID and no anaemia (n = 386, blue). Finally, patients with ID and no anaemia (n = 152, green) had a higher event rate compared with patients with no ID and no anaemia as well (45.8% vs. 33.0%). (C) Absolute ID was associated with the highest event rate after 10 years (61.3%) in men (n = 67, yellow), while men with functional ID (n = 76, green) or no ID (n = 315, blue) had a significantly lower cumulative event rate (50.7% and 42.4%, log‐rank test P = 0.005). (D) In contrast, functional ID was associated with the highest event rate (60.0%) in women (n = 20, green), while women with absolute ID (n = 65, yellow) or no ID (n = 131, blue) had a significantly lower cumulative event rate (32.7% and 31.8%, log‐rank test: P = 0.007).

Figure 2

Spearman rank correlations among selected parameters in CHF patients (n = 674). TSAT correlated with NT‐proBNP (A) (r _s = −0.271, P < 0.001) and CRP (B) (r _s = −0.239, P < 0.001) independent of sex, while ferritin levels correlated with NT‐proBNP (C) (r _s = 0.186, P = 0.009) and CRP (D) (r _s = 0.239, P < 0.001) only in women (n = 216).

Figure 3

Linkage of anaemia with the combined endpoint in various subgroups of 2223 patients with CHF (A) and linkage of iron deficiency with the combined endpoint in various subgroups of 674 patients with CHF and available iron metabolism parameters (B). Hazard ratio with lower and upper 95% confidence interval is shown.