Relative lymphocyte count is an independent predictor of death/urgent transplant in heart failure

Abstract

Objectives: Our aims were 1) to determine if low relative lymphocyte count (%L) is an independent predictor of death/urgent transplant and 2) to explore if the risk associated with low %L can be explained by neurohormones or cytokines. BACKGROUND Low %L is correlated with mortality in HF. However, there is little data on whether it is an independent predictor or potential mechanisms. Methods: Using a prospective cohort design, we evaluated the relationship between %L and mortality/urgent transplant in 129 outpatients referred to an end-stage HF clinic. Associations between %L and cytokines, neurohormones and clinical variables were examined to explore potential mediators or explanations for this relationship. Results: Patients with lower %L were older, more likely to have ischemic HF, lower blood pressure, higher creatinine, more comorbidites, lower peak VO2, higher JVP, lower hemoglobin, and higher leukocyte count. There was a positive association between %L and hemoglobin and inverse associations between %L and sTNF receptor 1, creatinine, JVP, leukocyte count, and age. There was a borderline inverse association with evening cortisol. The hazard ratio for mortality/urgent transplant in patients with %L<21.5 (median) was 6.61 (95% CI 2.5−17.3, p=0.0001). In a multivariate adjustment which included neurohormonones, cytokines, and cortisol, patients with low %L still had a more than 3-fold higher risk of death/urgent transplant (HR=3.4, 95% 1.1−10.8, p=0.04). %L was also strongly predictor when evaluated as a continuous variable, with more than 2-fold higher risk for each standard deviation lower %L (HR=2.59, 95% CI=1.44−4.69, p=0.002 multivariate model). Endotoxin induces apoptosis in erythroid cells, myocytes, and lymphocytes. We propose that low %L may be a marker of elevated circulating endoxotin levels. Unfortunately, endotoxin was not measured in this study. Conclusions: In patients with moderate to severe HF, low %L is an independent predictor of death/urgent transplant in HF. Further investigation into causative mechanisms for low %L in HF is warranted.Survival free of urgent transplant was markedly lower in patients with a low% lymphocyte count.