Anemia is strongly associated with immune activation in patients with coronary artery disease (CAD), and a combination of both anemia and increased markers for inflammation may drive higher rates of adverse outcomes among patients with CAD, according to a study led by Lukas Lanser, MD, of the Innsbruck Medical University in Austria.
According to the researchers, the data from this study suggest inflammation could be an underlying cause of anemia development in a significant proportion of patients with CAD. “Therefore, it might be useful to differentiate between patients with anemia of chronic disease, iron-deficiency anemia or multifactorial anemia to better predict their risks to die within the next years and to choose the best therapy option,” the researchers wrote.
The study was an analysis of patient data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, which included 3,316 patients with CAD who were hospitalized between 1997 and 2000. Hospitalization occurred because of chest pain or non-invasive test results suggestive of myocardial ischemia. Experienced angiographers examined patient angiograms and estimated the maximal luminal narrowing via visual
analysis.
Patients in the study were followed for 10 years. Researchers evaluated the event-free survival (EFS) rate, which was defined as the duration between first hospitalization and death. Additionally, the investigators examined markers of immune activation (i.e., neopterin, interleukin [IL]-12, IL-6, high-sensitivity C-reactive protein, fibrinogen, serum amyloid A), as well as iron metabolism (i.e., ferritin, transferrin saturation, hemoglobin).
The median age of the study population was 63.4 years. Approximately 68.7% of patients were men. Of the 960 patients with chronic CAD, the median age was 64.5 years, while the median age of patients with acute coronary syndrome (ACS) was 63.8 years. The median age among the 477 patients who did not have CAD was 60.6 years. At a median follow-up of 9.81 years, 18.4% of patients had died from cardio-cerebrovascular (CCV) disease and 10.5% of patients had died from diseases not related to CCV. A total of 12 patients were lost to follow-up.
Anemia was reported in 17.1% of patients (n=357), including those without CAD (8.6%), those with chronic CAD (16.1%) and those with ACS (25%). The presence of anemia was associated with severity of CAD as reflected by greater progressed stenosis in coronary angiography, Canadian Cardiovascular Society grading scale, and New York Heart Association classes, as well as a lower left ventricular ejection fraction. In addition, anemia was significantly associated with a higher CCV event rate and increased levels of inflammatory markers.
Anemia represented the only predictive variable for an adverse outcome in individuals with increased inflammatory markers. In an adjusted multivariate Cox regression analysis, anemia was associated with a significantly higher CCV mortality (hazard ratio [HR] = 1.348; 95% CI 1.052-1.727). Among those who had multifactorial anemia, patients with elevated inflammatory markers also had higher CCV mortality (HR=2.095; 95% CI 1.014-4.332).
In the two years that followed the index hospitalization, anemia of chronic disease was significantly associated with an increased cardiovascular event rate, compared with other types of anemia or no anemia (14.3 vs. 6.1 vs. 4.0%, respectively; p<0.001).
The presence of anemia was associated with a further increased risk for CCV-related mortality events in those with elevated levels of neopterin (HR=1.487; 95% CI 1.069-2.069) and those with an elevated neopterin to estimated glomerular filtration rate (eGFR) ratio (HR=1.737; 95% CI 1.346-2.241). In contrast, there was no association between anemia and CCV event rates in patients with a low neopterin/eGFR ratio.
“Our data suggest that the association of anemia with disease severity and outcome might mainly be due to underlying inflammation; additionally, advanced renal dysfunction should also be taken into account,” the researchers wrote.
Limitations of this study include its lack of data regarding neopterin levels, concomitant erythropoietin therapy, and blood transfusion.
Study authors report no relevant conflicts of interest.
Reference
Lanser L, Fuchs D, Scharnagl H, et al. Anemia of chronic disease in patients with cardiovascular disease. Front Cardiovasc Med. 2021;8:666638.
