NLR and MLR May Predict Gout Flare and CVD Mortality Risk

Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) may predict gout flare risk and increased risk of cardiovascular (CVD) mortality.1

“There remains a need for improved prognostic markers to help to stratify CVD risk in patients with gout, given that they have an increased risk of CVD-related morbidity and mortality. The NLR has been shown to predict cardiovascular mortality in rheumatoid arthritis (RA) and the NLR, along with the MLR is associated with disease activity in gout. Independent of underlying rheumatological disease, the NLR has shown a synergistic relationship with serum uric acid in increasing the risk of CVD mortality in patients with coronary artery disease. Therefore, it is possible that NLR as well as MLR can predict CVD risk in patients with gout,” lead investigator Ryan Stultz, MD, PhD, Clinician Researcher, Division of Rheumatology, University of Washington, Seattle, and colleagues wrote.1

The investigators previously demonstrated increased neutrophil activation, as measured by the neutrophil activation marker calprotectin, in patients with gout compared to healthy controls, in an earlier publication.2

Stultz and colleagues collected data from 38 participants with gout of the total 74 who participated in the “Reade gout cohort Amsterdam”, including disease activity as measured by total number of acute gout attacks, and 10-year risk of cardiovascular morbidity. They also measured calprotectin, cell counts, and uric acid levels from patients’ blood. The majority of participants were male (95%), and a majority had hypertension (61%).1

The investigators found that levels of the neutrophil activation marker calprotectin correlated with NLR (r = 0.56, P = .0004) and MLR correlated with total number of gout attacks (r = 0.39, P = .02). NLR and MLR, but not absolute monocyte or neutrophil counts, were significantly correlated with body mass index and significantly increased in gout patients with high CVD risk (P <.05). Logistic regression analysis revealed that patients in the upper quartile of NLR or MLR had increased odds of developing high CVD risk (odds ratio 7.5 [95% CI, 1.7–33.0]).1

“NLR and MLR are associated with an increased number of gout flares and elevations of either NLR or MLR predict CVD-related morbidity risk. As NLR and MLR are readily available laboratory tests, they may serve as useful biomarkers to assess gout flare risk and identify gout patients at risk of poor CVD outcomes to offer intensified monitoring and treatment,” Stultz and colleagues concluded.1

They acknowledged the study’s limitations, including that it does not evaluate the prospective development of high CVD risk in different gout patients over time and complete data on neutrophil, monocyte, and lymphocyte counts were not available for all patients.

“Future studies are warranted to determine the causal role of myeloid cell expansion and lymphocyte depletion in gout-related CVD, and to evaluate the link between high BMI and lymphocyte depletion,” Stultz and colleagues wrote.1

REFERENCES

1. Stultz RD, Dai L, van Geel E, Gerritsen M, Nurmohamed MT, Lood C. Elevated neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios are associated with increased flares and elevated cardiovascular disease risk in gout. Scand. J. Rheumatol. Published online January 17, 2025. doi.org/10.1080/03009742.2024.2421622

2. Vedder D, Gerritsen M, Duvvuri B, van Vollenhoven RF, Nurmohamed MT, Lood C. Neutrophil activation identifies patients with active polyarticular gout. Arthritis Res Ther 2020;22:148.