# Old and Novel Predictors for Cardiovascular Risk in Diabetic Foot Syndrome--A Narrative Review
## 4 Diabetic Foot Syndrome  
Diabetic foot (DF) is one of the most serious complications of diabetes with negative prognostic implications [10; 72; 73], being defined by the World Health Organization as ulceration of the distal leg of the ankle, including the ankle, associated with neuropathy and varying degrees of ischemia and infection [74]. DFS is defined as ulceration of the foot associated with neuropathy, ischemia and intermittent infections of any type [75; 76]. Diabetic foot can be classified from a pathophysiological and clinical point of view into several forms: ischemic diabetic foot, neuropathic ischemic foot and infected diabetic foot [77]. For diabetic patients, leg ulceration is the main cause of lower limb amputation. DM is also responsible for the majority of non-traumatic amputations, 85% of which are predisposed by foot ulceration [78; 79; 80]. The occurrence of ulcers in diabetic patients is accompanied by a high rate of morbidity and mortality, and also represents an economic and social burden through its implications for functional status and quality of life [81]. The prevalence of DF is about 6%, with recent epidemiological studies estimating the occurrence of an ulcer in at least 1 in 6 diabetic patients during their lifetime [82]. Men have a higher risk of developing DF compared to women [83; 84; 85; 86]. The recurrence rate of diabetic foot after healing is 30% [83; 87]. Based on these data and taking into account the high costs associated with medication and hospitalization, it has become necessary to develop primary or secondary prevention strategies to decrease mortality and acute vascular events in this category of patients [88]. The risk of developing diabetic foot is assessed using nomograms based on the main independent risk factors associated with it such as age, glycosylated hemoglobin, low density lipoprotein cholesterol, total cholesterol, smoking and alcohol consumption [80; 89; 90]. Several risk scores have been developed for diabetic patients prone to ulcers, which have both preventive and therapeutic roles [91; 92]. Diabetic peripheral neuropathy is the main promoter of ulceration in diabetic patients, leading to autonomic, motor or sensory alterations [93]. The increased cardiovascular risk of these patients results from the cumulative effect of associated neuropathy and peripheral arterial disease [94; 95]. The pathophysiological mechanisms involved are diverse, involving a variety of factors such as foot deformities, abnormal foot pressures, limited joint mobility, external trauma, peripheral arterial disease or edema (Figure 1) [96]. Sensory neuropathy may cause minor, repeated insults secondary to increased pressure or improperly felt mechanical and thermal stimuli [97]. Peripheral arterial disease causes a number of pathophysiological changes, both microvascular and macrovascular, which do not allow ulcers to heal. Clinical studies have shown that identifying an ankle-bracchial index of less than 0.90 correlates with a 1.25-fold increased risk of developing an ulcer in diabetic patients compared to a similar cohort of patients without peripheral vascular disease. Sleep apnea syndrome and nocturnal hypoxia are two risk factors associated with the development of diabetic peripheral neuropathy, the associated risk of these patients being 4 times higher [98; 99; 100]. The apnea-hypopnea index can be used as a marker for the presence of diabetic microvascular complications [101; 102]. Diabetic foot may be a marker of cardiovascular risk. The increased cardiovascular risk--and, therefore, the risk of complications and death in patients with diabetic foot--can be explained by biochemical alterations of the lipid and carbohydrate profile represented by hypercholesterolemia, the association of a serum LDL cholesterol level above 130 mg/dL, hypertriglyceridemia and microalbuminuria or even proteinuria [96]. [PERSON] et al.