Abstract

Abstract Background and Aims Patients with systemic lupus erythematosus have an increased risk of cardiovascular diseases (CVD) vastly contributing to morbidity and mortality. Besides traditional risk factors, lupus-related factors also contribute to the overall risk. Our major objective was to identify both traditional and non-traditional factors that could aid the prediction of CVD risk and major adverse cardiovascular events (MACE) in this population. MACE was defined as the composite of nonfatal myocardial infarction, hospitalization due to heart failure, coronary revascularization, stroke, and cardiovascular death. We also aimed to create a model that could be applied after a prompt assessment of lupus nephritis patients to estimate the long-term CVD risk. Method We conducted a single-center retrospective analysis on lupus nephritis patients. Demographic variables, cardiovascular events, clinical and histological data were collected from patients who underwent kidney biopsy between 2005 and 2020 (Figure 1). Chi-square, Mann-Whitney U-test, and logistic regression analyses were performed to investigate risk factors for MACE (IBM SPSS Statistics v28). Receiver Operating Characteristic (ROC) curve was used to determine optimal cut-off values. The study was approved by the Semmelweis University Regional and Institutional Committee of Science and Research Ethics (SE RKEB 225/2018). Results 91 patients were enrolled in this period. The mean age was 37.3±12.3 years, 86% females, and the mean follow-up time was 62±48 months. Fourteen patients (15.4%) suffered at least one MACE, of which 13 (14.3%) occurred after diagnosing lupus and 8 (8.8%) after the biopsy. Two patients deceased of a cardiovascular event. Out of the traditional risk factors, increased age (35.8±11.1 vs 45.5±15.1 years, p = 0.012) entailed a higher occurrence of MACE. Complete white blood cell (3.54±0.41 vs 3.25±0.87 Giga/liter, p = 0.026) and neutrophil count (2.85±0.33 vs 3.11±0.83 Giga/liter, p = 0.001) were higher, while diastolic blood pressure was lower (89.5±10.96 vs 78.43±6.9 mmHg, p<0.001) at the time of the biopsy in patients with MACE complication. Age, neutrophil count, and diastolic blood pressure were proven to be independent predictors of MACE (Table 1). Based on these observations, we proposed a new model (CANDE: Cardiovascular risk –based on Age, Neutrophil count, and Diastolic blood pressure– Estimation score) that is a stronger predictor of MACE and can be used to calculate MACE risk from the time of the biopsy in lupus nephritis patients (Figure 1). The higher the score was, the more often the MACE cases were present (Table 1). ROC curve analysis demonstrated that at 0.78 cut-off value the score predicts MACE occurrence at the time of the biopsy with a sensitivity of 0.75 and a specificity of 0.61. The analyses of MACE subgroups revealed that neutrophil-lymphocyte ratio was elevated in patients who were hospitalized because of heart failure (5.66±4.61 vs 9.68±6.46, p = 0.046), while neutrophil-thrombocyte ratio was higher in patients with coronary revascularization in their medical history (0.023±0.015 vs 0.06±0.028, p = 0.02). This also indicates the importance of neutrophils in CVD risk assessment. Conclusion Age, neutrophil count, and diastolic blood pressure are demonstrated to be independent risk factors of MACE in lupus nephritis. The score calculated from these parameters (CANDE) is a stronger predictor of MACE at the time of the biopsy. A larger cohort is needed to validate these promising results.

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