Baseline neutrophil-to-lymphocyte ratio and efficacy of SGLT2 inhibition with empagliflozin on cardiac remodelling

• Type of Material: Article
• Authors: Raj Verma, St Michaels Hosp Unity Hlth Toronto; Michael Moroney, St Michaels Hosp Unity Hlth Toronto; Makoto Hibino, Emory University; Cyril David Mazer, St. Michael's Hospital of Unity Health Toronto; Kim A Connelly, St. Michael's Hospital, Toronto Ontario, Canada; Andrew T Yan, University of Toronto; Adrian Quan, St. Michael's Hospital of Unity Health Toronto; Hwee Teoh, St. Michael's Hospital of Unity Health Toronto; Subodh Verma, St. Michael's Hospital of Unity Health Toronto; Pankaj Puar, St. Michael's Hospital of Unity Health Toronto
• Language: English
• Date: 2023-04-10
• Publisher: WILEY PERIODICALS, INC
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/ehf2.14351
• Title of Journal or Parent Work: ESC HEART FAILURE
• Volume: 10
• Issue: 3
• Start Page: 2127
• End Page: 2133
• Grant/Funding Information: The conduct of the EMPA‐HEART CardioLink‐6 trial was supported by an unrestricted investigator‐initiated study grant from Boehringer Ingelheim.
• Keywords: LEUKOCYTE COUNT; NLR; Science & Technology; Life Sciences & Biomedicine; Inflammation; SGLT2i; Cardiovascular System & Cardiology; Cardiac & Cardiovascular Systems; CORONARY-HEART-DISEASE; Left ventricular reverse remodelling; Type 2 diabetes
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery

Abstract

Aims: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and plays a critical role in the assessment and prognosis in patients with heart failure. The EMPA-HEART CardioLink-6 trial demonstrated that patients with type 2 diabetes (T2D) and coronary artery disease (CAD) treated with a sodium–glucose transport protein 2 inhibitor for 6 months experienced regression in left ventricular mass. Given this, we evaluated the relationship of baseline NLR and cardiac reverse remodelling in the entire cohort of this trial. Methods and results: A total of 97 individuals were randomized to receive empagliflozin (10 mg/day) or placebo for 6 months. The primary outcome of the trial was change in left ventricular mass indexed to body surface area (LVMi) from baseline to 6 months as measured by cardiac magnetic resonance imaging. In our analysis, the cohort was stratified above and below an NLR level of 2. To assess the treatment effect on the 6 month change in NLR, we used a linear model adjusting for baseline differences in NLR [analysis of covariance (ANCOVA)] that included an interaction term between the baseline NLR and treatment. To assess the treatment effect on the 6 month change in LVMi in each of the subgroups divided by baseline NLR, we used an ANCOVA adjusting for baseline differences in LVMi that included an interaction term between the subgroups and treatment. The results of the regression models were summarized as adjusted differences with two-sided 95% confidence intervals (CIs). Patients who exhibited an elevated baseline NLR demonstrated higher LVMi and left ventricular end-diastolic volume indexed to body surface area than those with a lower NLR. In patients with an NLR < 2 and NLR ≥ 2, the adjusted difference in LVMi between the empagliflozin- and placebo-treated patients was −2.98 g/m2 (95% CI: −6.18 to 0.22 g/m2) (P value = 0.067) and −4.43 g/m2 (95% CI: −8.50 to −1.11 g/m2), respectively (Pinteraction = 0.60). Conclusions: Empagliflozin treatment is associated with consistent reductions in LVMi in patients with T2D and CAD independent of baseline NLR.