AIMS: Prior evidence has implicated leucocyte expansion in several cardiovascular disorders, including heart failure (HF) with reduced ejection fraction (rEF). However, the prognostic importance of leucocyte count in HF with preserved EF (HFpEF) remains largely unexplored.
METHODS AND RESULTS: The Americas cohort of the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT-Americas) was used to evaluate the association between total leucocyte count and clinical outcomes in HFpEF. The primary outcome was a composite of aborted cardiac arrest, cardiovascular mortality, or hospitalization for HF. Secondary outcomes were hospitalization for HF, aborted cardiac arrest, stroke, non-fatal myocardial infarction (MI), cardiovascular mortality, non-cardiovascular mortality, and all-cause mortality. Survival models were used to identify the risk of the primary and secondary outcomes in those with leucocyte count above the median (7100 cells/μL), as compared to those with leucocyte count below the median, during the follow-up period. A total of 1746 (out of 1767; 99%) patients from TOPCAT-Americas were available for the analyses with a median follow up of 2.4 (25th to 75th percentile 1.4-3.9) years. Patients with leucocyte count >7100 cells/μL were 36% more likely to experience the primary endpoint compared to those with ≤7100 cells/μL (hazard ratio: 1.36, 95% confidence interval: 1.14-1.61). This association remained significant after extensive adjustment for potential confounders (hazard ratio: 1.27, 95% confidence interval: 1.06-1.52). We also observed a greater incidence of HF hospitalization and non-fatal MI in patients with higher leucocyte count. These associations remained robust on sensitivity analyses, suggesting a low probability of confounding. Exploratory analyses suggested that both higher leucocyte count (integrating the combined influence of both myeloid and lymphoid immune cells) and augmented platelet count (as a surrogate for myeloid immune cell expansion) in the same model were associated with the primary outcome (both P < 0.05).
CONCLUSIONS: Leucocyte count >7100 cells/μL was independently associated with adverse clinical outcomes in HFpEF patients from TOPCAT-Americas. These results were primarily driven by the HF hospitalization outcome but were also accompanied by an excess of non-fatal MI. Further research is needed to define the mechanisms underlying our findings and their prognostic implications.
Bibliographical noteFunding Information:
N.?S.?B. is supported by Walter B. Frommeyer Jr. Fellowship in Investigative Medicine awarded by the University of Alabama at Birmingham, American College of Cardiology Presidential Career Development Award, and National Center for Advancing Translational Research of the National Institutes of Health under award number UL1TR001417. S.?J.?S. is supported by NIH R01 grants HL107577, HL127028, HL140731, and HL149423, and #16SFRN28780016 from the American Heart Association. S.?D.?P. is supported by NIH R01 grants HL125735 and HL147549, and a VA Merit Award (I01 BX002706). This manuscript was prepared using TOPCAT Research Materials obtained from the National Heart, Lung, and Blood Institute.
N. S. B. is supported by Walter B. Frommeyer Jr. Fellowship in Investigative Medicine awarded by the University of Alabama at Birmingham, American College of Cardiology Presidential Career Development Award, and National Center for Advancing Translational Research of the National Institutes of Health under award number UL1TR001417. S. J. S. is supported by NIH R01 grants HL107577, HL127028, HL140731, and HL149423, and #16SFRN28780016 from the American Heart Association. S. D. P. is supported by NIH R01 grants HL125735 and HL147549, and a VA Merit Award (I01 BX002706).
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology
- Cardiovascular outcomes
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.