Key result
Various interventions, notably direct IL-6 inhibition, can modify the neutrophil-to-lymphocyte ratio, though current evidence does not establish it as a validated surrogate for cardiovascular benefit.
Why the study?
Do pharmacological, nutritional, lifestyle, and procedural interventions reduce the neutrophil-to-lymphocyte ratio in adults with established cardiovascular disease or elevated cardiovascular risk?
Systematic Review (n=1,741)
Do pharmacological, nutritional, lifestyle, and procedural interventions reduce the neutrophil-to-lymphocyte ratio in adults with established cardiovascular disease or elevated cardiovascular risk?
While the neutrophil-to-lymphocyte ratio is a modifiable inflammatory marker, current randomized evidence does not support its use as a therapeutic target or validated surrogate for cardiovascular benefit.
NLR modification by IL-6 inhibition and other interventions should not yet guide therapy or serve as surrogate; randomized evidence leaves cardiovascular validation open.
The neutrophil-to-lymphocyte ratio (NLR) is an accessible marker of systemic inflammatory activity associated with adverse cardiovascular outcomes, but whether it is modifiable through intervention and whether its reduction corresponds to cardiovascular benefit remain uncertain.This systematic review evaluated randomized evidence concerning the effects of pharmacological, nutritional, lifestyle, and procedural interventions on NLR among adults with established cardiovascular disease or elevated cardiovascular risk.MEDLINE via PubMed, Scopus, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for studies published from January 1, 2021, through July 31, 2026.Eligible studies included randomized controlled trials, randomized crossover trials, and secondary analyses of randomized trials reporting treatment-related changes in NLR.The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidance.Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, its crossover adaptation, and the Quality In Prognosis Studies (QUIPS) tool, where appropriate.Twelve studies involving 1,741 participants were included and synthesized narratively.Direct interleukin-6 (IL-6) inhibition produced the clearest dosedependent reduction in NLR, while glutathione, cardiac rehabilitation, time-restricted eating, curcumin, normobaric hyperoxia, and selected nutritional strategies also demonstrated potentially favorable effects.Findings for sodium-glucose cotransporter 2 inhibitors were inconsistent, with early empagliflozin initiation modulating inflammatory activity in one trial but producing no treatment-specific reduction in NLR during post-infarction recovery in another.Several studies associated lower inflammatory activity with improved ventricular function, global longitudinal strain (GLS), coronary plaque behavior, infarct volume, or neurological severity; however, few formally examined whether NLR independently predicted or mediated these effects.Clinical cardiovascular outcomes were infrequently reported and generally underpowered.Methodological limitations included small sample sizes, heterogeneous measurement schedules, post hoc analyses, multiple biomarker comparisons, and incomplete reporting of NLR outcomes.NLR appears to be a modifiable, context-dependent inflammatory marker, but current randomized evidence does not establish it as a therapeutic target or validated surrogate for cardiovascular benefit.Future trials should prespecify serial NLR assessments and determine whether phenotype-specific changes provide incremental prognostic or treatment monitoring value.
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Alemi et al. (2026) conducted a systematic review in Cardiovascular disease or elevated cardiovascular risk (n=1,741). Pharmacological, nutritional, lifestyle, and procedural interventions vs. Placebo, usual care, no intervention, active treatment, or delayed treatment was evaluated on Between-group or within-participant change in neutrophil-to-lymphocyte ratio (NLR). Various interventions, notably direct IL-6 inhibition, can modify the neutrophil-to-lymphocyte ratio, though current evidence does not establish it as a validated surrogate for cardiovascular benefit.
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