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Page 4 of 10 Archakova et al. Vessel Plus 2018;2:34 I http://dx.doi.org/10.20517/2574-1209.2018.52
Thus, hyperglycemia induces oxidative stress, which contributes to the accumulation of toxic products,
which in turn leads to atherogenic modification of m-LDL, endothelial dysfunction and atherosclerosis
progression in patients with diabetes.

NON-TRADITIONAL RISK FACTORS
Non-traditional risk factors in patients with diabetes on LTH, which play a huge role in the development of
vascular calcification (VC) and cardiovascular pathology in this group of patients, should not be overlooked.

CKD is more associated with non-traditional risk factors. They include impaired calcium-phosphate
metabolism, which can lead to VC. VC was found in patients receiving long-term dialysis, who also
[27]
demonstrated impaired calcium-phosphate metabolism . Secondary hyperparathyroidism (SHPT),
hypercalcemia and hyperphosphatemia are important links in the pathogenesis of VC in patients on LTH.

VC is a widespread complication of CKD and may lead to an increase in cardiovascular morbidity. VC is
divided into two types according to the localization of calcifications: calcification of the inner membrane
[28]
(intima) and the medial membrane (media) . Calcification of the intima is associated with an atherosclerotic
process. Risk factors for the development of atherosclerosis have been discussed above. Calcification of the
media (mediacalcinosis, Menkberg sclerosis) is observed in patients on LTH in the absence of risk factors for
atherosclerosis. The severity of VC may depend on many factors: the duration of hemodialysis therapy, the age
[29]
[30]
and degree of disorders in calcium-phosphate metabolism . In the works of Rumberger et al. hemodynamic
consequences of VC are presented: loss of elasticity of arteries, increase in pulse pressure, development of left
ventricular hypertrophy (LVH), HF, lower coronary artery perfusion and myocardial ischemia, which are the
[31]
main causes of death of the majority of patients with CKD. According to Ribeiro et al. , the prevalence of
calcification of the mitral and aortic valves (MVC and AVC) in patients on LTH is much higher than in the
[32]
control group comparable in age and sex. Thus, according to the results of Kalpakian et al. , coronary artery
[33]
calcification (CAC) was found in 53%-92% of patients with CKD. Raggi et al. showed that CAC is a predictor
of cardiovascular morbidity in elderly patients with CKD. The degree of CAC was associated with male sex,
diabetes and an increase in calcium-phosphate ratio.

It was revealed that CAC was much more common among patients on LTH, in comparison with patients
without CKD. A possible reason for this may be impaired calcium-phosphate metabolism, rather than
traditional risk factors, as previously believed [34,35] .

[36]
Komaba et al. , summarized the results of long-term follow-up study of patients on LTH, 38% of whom had
diabetes and had elevated levels of calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH).
Patients with Ca, P and iPTH levels exceeding target ones showed the highest cardiovascular mortality.

[37]
Research by Bellasi et al. included patients with end-stage CKD. All patients underwent electron beam
computed tomography (CT) for quantitative evaluation of CAC and calcification of the AVC on the Agatston
scale. Calcification of heart valves was assessed by two-dimensional echocardiography (echo). As a result, the
researchers concluded that patients who had valvular calcification or CAC had a higher risk of developing
[38]
cardiovascular diseases. Lee et al. studied factors that are associated with the calcification of the aortic
arch in patients on LTH. Calcification of the aortic arch was identified by X-ray. Patients were followed-
up for 10 years. The increase in calcification was associated with age, higher levels of Ca and blood glucose.
During the follow-up period, the authors found that the degree of calcification of the aortic arch was directly
[39]
related to cardiovascular mortality. According to the data of instrumental studies, Volkov et al. have
shown that coronary heart disease in 55.6% of patients and HF in 50.0% of patients on LTH. Combination of
MVC and AVC was predominant. Valve calcification was more often observed in older patients, with longer
dialysis treatment, more pronounced SHPT, inflammatory changes, and atherosclerosis. Calcification of