Title: Lymphocyte-to-Monocyte Ratio is Mediated in Age-Related Cardiovascular Mortality in HFpEF: Immunosenescence, Inflamm-Aging, and Longevity
Abstract: Background: Age-dependent changes in the immune system contribute largely to mortality in mostchronic diseases, including heart failure with preserved ejection fraction (HFpEF). The absolutenumbers of lymphocytes and monocytes have been reported to change with age, both of which arecritical in the pathogenesis of HFpEF. Thus, the present study was performed to examine theassociation between lymphocyte-to-monocyte ratio (LMR) and clinical outcomes of HFpEF andexplore the mediation role of LMR in the relationship between age and major adverse events ofHFpEF.Methods: From May 2015 to December 2023, a sample of 1274 HFpEF inpatients from the REDCARPETtrial who underwent more than one ultrasound cardiogram were included. Mortalityfollow-up was complete until December 2023. We investigated associations of age with mortalityusing multivariable-adjusted Cox proportional hazard regression and restricted cubic spline analysis.Next, correlations of baseline LMR with all-cause death and cardiovascular death were examinedby Cox regression and restricted cubic spline analysis. Finally, Causal mediation analyses wereperformed to assess the mediating role of LMR in the association of age with the clinical outcomesof patients with HFpEF.Findings: During a median follow-up of 4.9 years, 166 out of 1274 had all-cause death and 82 hadcardiovascular death. After adjusting for all covariates, per 1-SD increase in age was associated witha 1.98-fold (95%CI, 1.66-2.35) risk of all-cause death and a 1.73-fold (95%CI, 1.36-2.21) risk ofcardiovascular mortality. In fully adjusted models, the highest tertile of LMR was associated withlower odds of all-cause death (HR: 0.42 [0.27-0.65], p=0.002) and cardiovascular death (HR: 0.23[0.12-0.46], p<0.001). We observed the robust associations in the restrict cubic spline analyses.Finally, causal mediation analyses suggested that LMR was partially mediated the correlation(mediation proportion 11.0% [95%CI 4-25]) between age and cardiovascular death patients withHFpEF.Interpretation: Causal mediation analysis potentially provides an estimate of the mediating role ofLMR in age-related cardiovascular death in patients with HFpEF. Our findings suggest thatimmunosenescence and inflamm-aging are potential mechanisms of adverse outcomes of HFpEF.Funding: This study was supported by the National Natural Science Foundation of China (82070384, 82370358 to X.Liao), Guangdong Basic and Applied Basic Research Foundation (2024A1515013234 to X.Liao; 2024A1515012356 to X.Zhuang; 2022A1515010416, 2024A1515030241 to Y.Guo; 2022A1515111181 to M.Liu); Funding by Science and Technology Projects in Guangzhou (2023A04J2169 to Y.Guo) and China Postdoctoral Science Foundation (2022M723635 to M.Liu).Declaration of Interest: Xiaojie Cai, Menghui Liu, Chong Feng, Sanhua Tang, Peng Qin, Yubin Li, Teng Wang, Lixiang He, Jiangjie Lei, Yi Zhou, Yue Guo, Xiaodong Zhuang and Xinxue Liao declare that they have no conflict of interest.Ethical Approval: This study was performed following the Declaration of Helsinki and was approved by the Ethics Review Committee of the First Affiliated Hospital of Sun Yat-Sen University.
Publication Year: 2024
Publication Date: 2024-01-01
Language: en
Type: preprint
Indexed In: ['crossref']
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