# Old and Novel Predictors for Cardiovascular Risk in Diabetic Foot Syndrome--A Narrative Review
## 5 Discussions
### Cardio-Diabetology: The Role of Biomarkers and Inflammatory Molecules
While IL-18 and soluble E-selectin are associated with reduced vagal activity, adiponectin can be used as a marker of decreased sympathetic activity [151]. Adiponectin has a dual, titer-dependent role, being both a cardioprotective hormone with an anti-inflammatory role and a marker of high cardiovascular risk through its association with an assessment of the risk of death [152; 153]. Adiponectin also prevents cardiac remodeling after myocardial infarction and inhibits the action of the sympathetic nervous system on this pathophysiological process, also having a potential therapeutic role in these patients [154]. [PERSON] et al. [155] demonstrated that elevated serum adiponectin levels are an independent predictor of atrial fibrillation in women and men under 65 years old. Figure 2: Pathophysiological mechanisms involved in the occurrence of cardiovascular disease in diabetic patients (adapted from [135]). Peripheral somatic neuropathy contributes to the development of medial arterial calcification [156]. In diabetic patients, it plays a role in activating the receptor activator of nuclear factor kappa B ligand/osteoproteger signaling pathway that modulates the pathophysiological processes involved in the calcification of smooth muscle cells in the coronary arteries and peripheral limbs [130]. Advanced glycation end-products also contribute to the production of vascular calcification and, thus, to the progression of atherosclerotic lesions in diabetic patients [157; 158]. Serum B-type natriuretic peptide levels correlate with the risk of onset and progression of diabetic neuropathy, but further clinical research is needed to unravel any pathophysiological implications. Data in the literature to date attest to the role of this cardiovascular biomarker in identifying and assessing the extent of neuropathic damage in diabetic patients. Based on the role of BNP to assess the presence of systolic and diastolic dysfunction as well as to assess the prognosis of patients with heart failure, the identification of a connection with DFS is of great clinical importance, as it can also assess the cardiovascular risk of patients without previously known cardiac pathology [159; 160; 161]. [PERSON] et al. [162] demonstrated that serum BNP levels were higher in patients with type 2 DM and diabetic neuropathy compared to a cohort without microvascular damage (\(p\) = 0.001), while positively correlating with systolic blood pressure, serum creatinine, prevalence of diabetic ulcers (\(p\) = 0.039) and vibration perception threshold values (\(p\) = 0.021). Identification of a BNP value above 15.18 pg/mL has a sensitivity of 78.7% and a specificity of 48.2% in assessing the presence of diabetic neuropathy. A recently published meta-analysis by [PERSON] et al. [163] highlights that the presence of a serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) level above 225 pg/mL correlates with a high risk of death from any cause among diabetic patients, while serum levels above 100 pg/mL are predictive of the occurrence of acute cardiovascular events. This biomarker, along with IL-6 and resistin, correlates with the presence of left ventricular dysfunction and left ventricular hypertrophy and can thus be used as non-invasive biomarkers for assessing cardiovascular risk in patients with DM [164].