T2DM is an independent risk factor for CV diseases, and CV complications are the leading cause of death in DM patients [11]. Therefore, determining predictive parameters for death and MACE in patients with T2DM is important to identify high-risk patients, intensify treatment, follow-up of the patient, and estimate prognosis. The HANBAH score has been previously shown to independently predict mortality in patients with acute HF [7, 8]. In previous studies, the relationship between the parameters that make up the HANBAH score and mortality and MACE in DM patients has been examined. However, the effect of the HANBAH score on mortality and MACE in DM patients has not been examined. Therefore, in our study, the relationship between DM mortality and MACE and HANBAH scores was examined. To our knowledge, our study is the first study conducted between the HANBAH score and DM. A significant and independent relationship was observed between the HANBAH score, which is simple, cheap and easy to calculate, and T2DM mortality and MACE.
In our study, with long follow-up period and large patient population, Cox regression and ROC analysis and Kaplen Meier analysis showed that HANBAH score can be used for mortality and MACE prediction. In the ROC analysis performed in our study, HANBAH score was a strong predictor of mortality. Moreover, since the number of mortality was low, that is, there was a difference in number between the mortality group and the survival group, and the number was further reduced with propensity score matching, matching analysis could not be performed, and in order to support the HANBAH score as a good predictor of mortality, a more sensitive method, sensitive recall curve analysis, was performed in these conditions and the results were strengthened.
Anemia is a common finding in DM patients. It has also been reported that anemia is associated with an increased risk of CV disease by reducing myocardial oxygen delivery and creating oxidative stress [12]. Additionally, anemia is associated with adverse clinical outcomes in DM patients, and Correction of anemia in DM patients resulted in improvements in clinical outcomes [13]. Therefore, low Hb levels is significant in mortality and MACE in DM patients.
Aging is associated with an increased risk for macrovascular and microvascular complications, mortality, and MACE, along with an increased prevalence of DM [14]. Because comorbid diseases increase with age, physical activity decreases, glycemic control becomes difficult in DM patients, and adverse clinical results are seen [15].
HT and CKD are commonly observed in patients with DM. Therefore, blood pressure control and sodium balance are critical in DM patients [16]. Sodium levels are impaired in patients with CKD, and hyponatremia, in particular, is associated with adverse CV outcomes [17]. Another parameter, BUN, is a product of protein metabolism and is often used to assess kidney function. It has even been shown that BUN is a better predictor of CV diseases than creatinine [18]. In addition, some studies have observed that BUN is associated with all-cause and CV-related deaths in patients with or without DM [19]. There are some hypotheses about the relationship between DM and BUN. Since glucose metabolism is related to the renal pathway, abnormal BUN levels, indicating renal dysfunction, are closely related to glucose levels. Additionally, increased urea levels in the circulation have been shown to affect pancreatic beta cells, reducing insulin secretion and thus being associated with the development of DM [20]. An association between elevated BUN levels and stroke risk has also been reported [21]. For these reasons, increases in BUN levels and hyponatremia may increase the risk of mortality and MACE in DM patients.
It is known that high low-density lipoprotein (LDL) and low HDL cholesterol levels in dyslipidemia are associated with increased CV risk [22]. Studies examining the relationships between HDL levels and CV outcomes in T2DM patients have found different results [23]. For this reason, the latest guidelines have stated that increasing HDL levels does not show evidence that it will reduce the risk of cardiovascular disease and that there is no clear clinical evidence of the positive effects of HDL-raising treatments [24]. HDL has various positive effects, such as antioxidants, anti-inflammatory effects, and enhancement of endothelial function [25]. Low HDL or elevated non-HDL cholesterol may relate to higher mortality and MACE rates by contributing to vascular endothelial dysfunction, oxidative stress, increased inflammation, and a greater risk of atherosclerosis [26]. Therefore, low HDL cholesterol increases the predictive value of the HANBAH score, which includes this parameter for mortality and MACE.
AF is the most common arrhythmia, with increasing incidence worldwide. Additionally, DM and AF are associated with an increased risk of death, MI, and MACE [27]. There are several theories to explain this relationship. First, increased inflammation and oxidative stress have been implicated [28]. Second, DM and AF may induce cardiac profibrotic pathways [29]. Third, DM and AF may cause CV complications through endothelial dysfunction and prothrombotic effects [30]. In addition, adverse clinical outcomes may occur as a result of HF caused by AF, tachycardia, and increased left atrial pressure [31]. For these reasons, the HANBAH Score can be critical in determining DM mortality and MACE.
Considering the effects of hemoglobin, age, sodium, BUN, AF history and HDL parameters included in the HANBAH score on DM mortality and MACE, it was expected that combining them into a single score would be more highly associated with DM mortality and MACE. Our ROC Curve analysis revealed that the HANBAH score had significantly better predictive power than both the independent risk scores and the parameters comprising the HANBAH score. Therefore, the HANBAH score, which includes parameters previously shown to have prognostic significance in DM patients in various studies, was determined to be a stronger and better prognostic indicator. Furthermore, this score, with its ease of calculation and robust prognostic value, could significantly benefit clinical practice and be used for risk stratification in a disease with a high incidence and complications such as DM. While not currently a recommended mortality score for DM patients, our study is the first to examine the relationship between the HANBAH score and DM mortality and MACE and may serve as a starting point for future, more comprehensive studies.
Chronic inflammation is frequently found in patients with DM and plays a role in CV disease pathogenesis by increasing hypoxia or oxidative stress [32]. Additionally, many hematological and inflammatory parameters have been investigated, suggesting that inflammation may play an essential role in developing T2DM complications [33]. However, few of these studies have investigated the prognostic significance of these parameters for MACE. Aside from the HANBAH Score and its parameters, CRP was significantly linked to mortality as an inflammatory marker, but no significant relationship was found with MACE.
Albumin level is an important marker of nutritional status, malnutrition, and inflammation. Its association with DM mortality and MACE has been previously demonstrated [34]. In our study, albumin was significantly associated with mortality and MACE. Although albumin was an independent predictor of MACE in the regression analysis, no independent relationship was observed with mortality.
Hyperglycemia is known to be associated with increased morbidity and mortality in patients with MI, HF, COPD, stroke, and critical illness [35,36,37,38]. In addition, HbA1c, an indicator of chronic glucose levels, is associated with MACE and mortality [39]. In our study, glucose levels at hospital admission were significantly associated with mortality and MACE but lost significance in multivariable Cox regression analysis. HbA1c and MACE were related; however, the multivariable Cox regression analysis did not show a significant relationship.
The starting point of our study was to evaluate the effect of the HANBAH score with the idea of whether there could be a scoring system that could predict DM mortality and MACE risk. There is no recommended scoring method to predict DM mortality and MACE risk, and there are limited studies on this subject in the literature. For example, GRACE, TIMI, PAMI and CADILLAC scores were used to evaluate mortality in DM patients with acute coronary syndrome [40, 41]. Since our study consisted of DM patients without acute coronary syndrome, comparisons could not be made with these scores. In the future, HANBAH scores can be compared with different scoring systems in different populations in DM patients.
Limitations
This study is the first to evaluate the predictive value of HANBAH score for mortality and MACE in patients with T2DM. It is also a study predicting important clinical outcomes such as mortality and MACE in T2DM patients with a large population and long-term follow-up period. However, our study has several limitations. Due to the retrospective observational nature of the study, prospective studies are needed to establish a causal relationship between mortality and MACE in patients with T2DM. Second, despite adjustments in our multivariable Cox regression analysis, the existence of unmeasured (such as diet, medication doses, and duration of physical activity) or confounding (such as smoking and alcohol use) factors cannot be excluded. Patient data on important cardiovascular risk factors such as smoking, alcohol use, socioeconomic status, and physical activity were not available due to retrospective analysis, and the effect of these characteristics could not be determined. In addition, since it is not known whether the drugs were used regularly and completely and in what dose due to the retrospective nature of the analysis, a significant difference in terms of mortality may not have been detected. Third, most of the participants in our study were relatively low-risk outpatients and middle-aged patients. Although we expect the predictive value of the HANBAH score to increase further in the riskier and older group, where we expect higher mortality and MACE rates, it may limit the generalizability of our study and studies may be required in this patient group. In addition, in our study, propensity score matching could not be done due to the decrease in the number of patients.