CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 2, May/June 2023 AFRICA 107 Discussion Coronary atherosclerosis is a chronic inflammation of the coronary arterial wall that usually occurs due to abnormal lipid metabolism and inappropriate immunological reactions. LOX-1 is a 50-kDa, C-type lectin family transmembrane glycoprotein. It is well recognised that LOX-1 is essentially involved in the many pathophysiological steps of atherosclerosis. In normal physiological conditions, LOX-1 expression is very low, but its level is markedly up-regulated in various cardiovascular disease conditions.3,16 This study identified that relative expressions of circulatory sLOX-1 were more amplified in patients with stable and unstable CAD than in healthy subjects. The expression levels of sLOX-1 within the stable and unstable CAD groups were also noticeably changed. Furthermore, sLOX-1 levels in both male and female stable and unstable CAD patients were statistically significantly different compared to the controls. Stankova et al. reported that sLOX-1 values in stable CAD patients were increased, and sLOX-1 could act as a potential biomarker for the diagnosis of CAD patients and possibly those with the metabolic syndrome.4 Our recent coronary artery research has demonstrated that concentrations of LOX-1 were significantly elevated in a stable CAD group and it was associated with subjects with the metabolic syndrome.17 Synetos et al. found sLOX-1 values were dramatically higher in male three-vessel CAD patients.18 Lubrano’s research group investigated LOX-1 expressions that were closely linked with oxidative stress and evidently increased in stable CAD patients.7 It has also been demonstrated that high serum soluble LOX-1 concentrations have a significant clinical effect for the diagnosis of CAD and aortic dissection patients.19 Peripheral circulatory sLOX-1 concentrations were potentially up-regulated in patients with rupture of atherosclerotic plaque and in patients with acute coronary syndrome.20,21 Zhao’s research group found that serum sLOX-1 concentrations in stable CAD patients were much higher than in the controls. A significant relationship with coronary angioplasty with a subsequent two-year follow up suggested sLOX-1 as a diagnostic and prognostic biomarker.10 Furthermore, it has recently been shown that sLOX-1 gene expressions in the plasma of carotid artery atherosclerosis and ischaemic stroke patients were prominently elevated compared with the controls. High levels of sLOX-1 were also significantly associated with carotid plaque inflammation.22,23 In the present research, the diagnostic value of plasma sLOX-1 was analysed with the ROC curve and we found that stable and unstable CAD patients were clearly differentiated from the control group. In addition, AUC in stable and unstable CAD subjects (0.867) was also highly sensitive and statistically significantly different, which endorses elevated plasma sLOX-1 level as a promising novel non-invasive clinical biomarker for CAD patients. These results are also corroborated by other research findings.9,12,24 To my knowledge, this study is the first to report concentrations of circulating sLOX-1 that were obviously higher in healthy female, and stable and unstable CAD subjects between 61 and 84 years than in younger healthy female and male subjects, and stable and unstable CAD participants of 30 to 60 and 61 to 84 years. In a baseline clinical study, we noticed C-reactive protein levels were significantly different in healthy subjects and stable and unstable CAD patients but baseline data of other researchers were not statistically significantly different. Therefore, there is a need for further study to find the underlying molecular mechanism and relationship with sLOX-1 and C-reactive protein expression. To avoid possible errors during our selection of the study subjects, similar ages were chosen for all healthy and CAD groups between 30 and 84 years. In our study we collected CAD patients’ blood samples three days after the coronary Sensitivity 1.0 0.8 0.6 0.4 0.2 0.0 1 – Specificity 0.0 0.2 0.4 0.6 0.8 1.0 AUC: 0.895 Sensitivity 1.0 0.8 0.6 0.4 0.2 0.0 1 – Specificity 0.0 0.2 0.4 0.6 0.8 1.0 AUC: 0.902 AUC: 0.867 Sensitivity 1.0 0.8 0.6 0.4 0.2 0.0 1 – Specificity 0.0 0.2 0.4 0.6 0.8 1.0 Fig. 3. The area under the ROC curves was used for evaluation of plasma sLOX-1 as a laboratory marker for diagnosis of CAD patients. A: Healthy subjects versus stable CAD patients (AUC: 0.895) (p < 0.001). B: Healthy subjects versus unstable CAD patients (AUC: 0.902) (p < 0.001). C: Stable CAD versus unstable CAD patients (AUC: 0.867) (p < 0.001). Table 2. ROC analysis results for evaluation of CAD patients Plasma LOX-1 Sensitivity, % Specificity, % Cut-off point Positive predictive value Negative predictive value Confidence interval (95%) AUC p-value Healthy subjects vs stable CAD 0.95 0.85 1.804 226 75 0.844–0.945 0.895 < 0.001 Healthy subjects vs unstable CAD 0.92 0.88 1.808 138 75 0.854–0.950 0.902 < 0.001 Stable vs unstable CAD 0.77 0.86 1.635 138 226 0.822–0.912 0.867 < 0.001 ROC, receiver operating characteristics; AUC, area under the curve; CAD, coronary artery disease. A B C
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