Several clinical studies have shown a lot of attention about SAF measurement for predicting both microvascular and macrovascular complications in diabetic patients. This cross-sectional study showed that SAF levels were increased in HD patients and the value was markedly increased in HD patients with diabetes or combined with hypertension or dyslipidemia. Furthermore, HD patients with heart failure showed a significant increased SAF compared to HD patients without heart failure. Studies showing the relationship between SAF and CVD in HD patients are limited and reported that SAF is the independent predictor for overall mortality in HD patients [11, 16, 17]. However several studies have shown the strong association between SAF, CVD and CKD [18–21]. For patients on peritoneal dialysis, one study showed that more deaths were observed in group with high SAF than in group with low SAF group. The SAF values over 3.61 provide a reliable cut-off for predicting three years mortality [22]. The SAF showed to be correlated with the duration of dialysis and glucose exposure dose and independently associated with cardiovascular morbidity [23]. An explanation for the predictive value of SAF could be the main role of AGEs in the development of vascular complications in diabetes mellitus, renal failure and CVD. Besides decreased clearance of AGEs in patients with renal failure, AGEs formation is accelerated throughout the years during dialysis, resulting in progressive AGEs cross-linked to long-lived proteins which may contribute to endothelial dysfunction [24, 25].
Measurement of SAF can indicate tissue alterations long before they would be revealed by conventional screening methods or cause clinical signs [26]. To shed light, SAF may represent a clinically useful, noninvasively method and fast results for assessing heart failure in HD patients. We observed a significant increased of SAF levels in HD patients with heart failure compared to those without heart failure. Furthermore, to predict the presence of HF in HD patients, we found that the cut-off point of SAF value is was at 3.05 AU. This study demonstrated that SAF > 3.05 AU was an important predictor for the presence of HF. Remarkably, this level is the same as used by Wang et al. for predicting abnormal flow-mediated vasodilatation (an indicator of endothelial dysfunction) in uremic subjects on hemodialysis [17]. Previous studies have found an association between SAF and the pathogenesis of HF in diabetic patients without HD. SAF may be a prognostic factor in patients with long-standing persistent atrial fibrillation and the risk value of SAF was considered as 2.6 AU for high CHADS2 score and SAF value at 2.7AU for elevated high sensitivity cardiac troponin levels [27]. Furthermore, SAF can predict the risk of the first HF hospitalization in patients with preserved ejection fraction and the cut-off point of SAF was determined to be > 2.9 AU [28].
In the present study we found significant associations between SAF levels and age, gender and duration of dialysis. Our finding is a line with several studies [11]. McIntyre et al. reported in a cohort of 1707 patients with CKD class III that a large number of cardiovascular and renal risk factors were associated with SAF, such as eGFR, hemoglobin, smoking, total cholesterol, diastolic blood pressure, c-reactive protein, albuminemia, pulse wave velocity, diabetes, and uremic acid [13]. Recently, Shardlow et al. have investigated in a large prospective cohort study that SAF was an independent risk factor for cardiovascular events and all-cause mortality in persons with early CKD [21]. This new finding supports the usefulness of SAF measurement as predictor biomarker for clinicians to detect early disease and monitor patient’s health over time.
Some limitations of this study should be noted. This study was conducted at a single center with a relatively small sample size and the value of SAF in predicting for the presence of heart failure could not confirmed in this cross-sectional study, which requires further follow-up.
In conclusion, this study indicates that SAF was associated with the presence of heart failure in Tunisian HD patients. Noninvasive measurement of SAF might be a good surrogate marker for evaluating heart failure. Further investigations in a large number of prospective studies are required to validate the results in this study.