Background: Systemic autoimmune diseases, including systemic sclerosis (SSc), are associated with early atherosclerosis. Hematological indices, such as: Neutrophil-Lymphocyte Ratios (NLR), Platelet-Neutrophil Ratios (PNR) and Platelet-Lymphocyte Ratios (PLR), are related to systemic inflammation and atherosclerosis. In SSc, NLR could predict disease progression and mortality.

Objectives: To evaluate the potential value of baseline NLR, PNR and PLR determination as predictors of subclinical vascular damage (atherosclerosis), major adverse cardiovascular events (MACEs), disease severity and mortality in SSc patients. To establish a theoretical cut-off value, that allows to identify patients with an increased risk of atherosclerosis, MACEs and death.

Methods: All patients from a longitudinal SSc cohort followed at a hospital in eastern Spain between 1984 and 2023 were included. The NLR, PNR and PLR ratios were calculated using their initial diagnostic blood test. Epidemiological, clinical, laboratory and radiological findings were obtained by examining the patients’ medical histories. The presence of atheromatous plaques (subclinical atherosclerosis) was evaluated using extracranial carotid artery ultrasound (ESAOTE MyLab XV70) or radiological studies (pulmonary HRCT). The appearance of MACEs, before and/or after the diagnosis of SSc, as well as fatalities, was recovered from patient’s clinical records. In case of death, the cause (attributable or not to the disease) was registered. The statistical analysis was performed using SPSS 17.0 program.

Results: The cohort consists of 175 patients, 93% women, 80% were classified as limited cutaneous SSc and 20% as diffuse cutaneous SSc, with an average age at diagnosis of 53 years (SD ± 16.07). 35% had dyslipidemia, 33% had arterial hypertension, and 7% had diabetes mellitus. Of the total patients included, 49% exhibited subclinical atherosclerosis. The mean follow-up of 10 years (SD ± 7.84) and the average disease duration from the first non-Raynaud symptom was 22 years (SD ± 10.50).

19% of the patients experienced one or more MACEs (50% cardiac, 32% peripheral, and 29% cerebral) and 22% of the patients passed away. Only 29% of the deaths were related to SSc; from the remaining, 37% resulted from vascular events.

The mean values of NLR, PNR and PLR were 2.44 (SD ± 1.53), 64.17 (SD ± 27.61) and 139.83 (SD ± 90.63), respectively. In our cohort, higher NLR values were significantly associated with the development of subclinical atherosclerosis (p = 0.001), a higher number of MACEs (p = 0.019), and overall mortality (p = 0.000), both vascular (p value = 0.026) and attributable to SSc (p = 0.034). Values above 2.09 were associated with increased mortality in our patients (AUC = 0.714; p = 0.000) with 74% sensitivity and 58% specificity.

Lower PNR values were significantly associated with the development of subclinical aterosclerosis (p = 0.005), and overall mortality (p = 0.000), but it was not significantly associated with MACEs. Values below 59.97 were associated with increased mortality in our patients (AUC = 0.324; p = 0.048) with 63% sensitivity and 57% specificity. We found no relationship between PLR and the studied variables.

Conclusion: Baseline NLR and PNR determination can be useful in predicting atherosclerosis and mortality in SSc patients. Higher values of NLR are associated to a higher and more fatal number of MACEs. We established cut-off values for NLR and PNR in our cohort, with a good internal validity for the studied clinical events.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.