Abstract
Objective: Anemia is often found in patients with coronary artery disease (CAD) or acute coronary syndrome (ACS) and related to disease severity. Our study investigated the relationship between anemia, iron homeostasis and inflammation in CAD and examined their influence on the outcome of patients.Patients and Methods: Markers of immune activation (neopterin, interleukin [IL]-12, IL-6, high sensitive C-reactive protein (hsCRP), fibrinogen, serum amyloid A [SAA]) and iron metabolism (ferritin, transferrin saturation, hemoglobin) were determined in 2,082 patients (68.7 % men, median age 63 years) from the Ludwigshafen Risk and cardiovascular Health (LURIC) cohort. Patients were followed-up for a median of 9.81 years.Results: 960 patients (46.1 %) presented with chronic CAD, 645 patients (31.0 %) had an ACS, and 477 patients (22.9 %) presented with no CAD in coronary angiography (CAG). Anemia (n = 357, 17.1 %) was associated with disease severity (reflected by more progressed stenosis in CAG, CCS, and NYHA classes, and a lower LV-EF), a higher cardio-cerebrovascular event rate and higher levels of inflammatory markers. Interestingly, anemia was only predictive for an adverse outcome in patients with elevated inflammatory markers. Accordingly, anemia of chronic disease (ACD) was associated with a higher cardio-cerebrovascular event-rate in the subsequent 2 years as compared to patients with other types of anemia or without anemia (14.3 vs. 6.1 vs. 4.0%, p < 0.001).Conclusions: This study confirms that anemia and immune activation are strongly related to cardiovascular disease progression and an adverse outcome. Our data suggest that the association of anemia with disease severity and outcome might mainly be due to underlying inflammation.
Highlights
Anemia and iron deficiency (ID) are frequently encountered in patients with coronary artery disease (CAD) and acute coronary syndrome (ACS) and are both related to a poor prognosis [1, 2], a reduced functional capacity and a reduced healthrelated quality of life of patients [3, 4]
We studied patients according to the different types of anemia
We could show for the first time that the underlying cause of anemia has a significant impact on the prognosis of patients: anemia of chronic disease (ACD), which is caused by immune activation, is associated with a significantly higher risk for cardio-cerebrovascular events in the subsequent 2 years when compared to patients with iron deficiency anemia (IDA) or multifactorial anemia
Summary
Anemia and iron deficiency (ID) are frequently encountered in patients with coronary artery disease (CAD) and acute coronary syndrome (ACS) and are both related to a poor prognosis [1, 2], a reduced functional capacity and a reduced healthrelated quality of life of patients [3, 4]. In many patients enhanced formation of pro-inflammatory cytokines including interleukin 1 (IL-1), tumor necrosis factor alpha (TNF-α) or interferon gamma (IFN-γ ) leads to the development of functional iron deficiency (ID) and anemia of chronic disease (ACD) [5]. These pro-inflammatory cytokines suppress renal erythropoietin production, and directly inhibit erythropoiesis in the bone marrow [6,7,8]. Iron restriction within macrophages limits iron availability for erythropoiesis leading to anemia [9]
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