RISK FACTORS FOR DEVELOPMENT OF CARDIOVASCULAR COMPLICATIONS IN PATIENTS WITH CHRONIC RENAL DISEASE AND DIABETIC NEPHROPATHY

Introduction: Cardiovascular diseases are the most frequent causes of morbidity and mortality in patients with chronic renal disease. R e aim of our paper is to evaluate the risk factors of cardiovascular complications in patients with various stages of chronic renal disease (CRD), with or without diabetes mellitus (DM). Patients and methods: R e study included  patients with diff erent stages of the CRD, with creatinine clearance < ml/min/,m, and laboratory parameters monitored: homocysteine, BNP, cholesterol, LDL, HDL, HbAc, Body Mass Index (BMI). First group comprised  patients with DM, age - years, M /F . Second group comprised  patients without DM, age - years, M /F . R e IMT (intima media thickness) was measured by B-mode ultrasonography, and all patients had echocardiography examination done by D Doppler ultrasonography. Results: R e IMT values in diabetic patients had statistically signifi cant positive correlation with homocysteine values of r=,, p<,, and cholesterol r=,, p<,, compared to non-diabetics. A signifi cant negative correlation was found between the ejection fraction (EF) and BMI in both groups, more prominent in non-diabetics r=,, p<, (diabetics r=,, p>,). , of diabetics had arteriosclerotic changes on carotid arteries, , had stenosis of ACC, and , had rhythm abnormalities on ECG. A positive correlation between IMT and BMI was found in diabetics, but was not statistically signifi cant r=,, p>,. In the diabetics group a signifi cantly higher (p<,) values of BNP, HbAc, proteinuria, BMI, and cholesterol were found, and signifi cantly lowered


Introduction
Diabetic nephropathy is one of the most significant complications of diabetes mellitus and also the most frequent cause of end-stage renal insufficiency.The number of patients who end up on an active haemodialysis treatment increased by  in the last  years.Cardiovascular complications, induced by accelerating arteriosclerosis, comprise almost  of all morbidity and mortality causes in diabetics, and patients with renal insufficiency caused by diabetes have an increased risk of cardiovascular complications ().It is well-known fact that the traditional risk factors for cardiovascular disease are: diabetes mellitus, anemia, microalbuminuria, proteinuria, azothemia, hyperlipidemia, obesity, smoking, physical inactivity, and nontraditional factors are: metabolic and hemodynamic disturbances.Combined impact of diabetes mellitus and a renal disorder increased the risk of cardiovascular (CV) complications and off er poorer prognosis for survival of these patients compared to general population.ere are a number of hemodynamic and metabolic disorders in diabetic nephropathy, which disturb the structure and function of myocardium, and the progressive hypertrophy of the left ventricle (LVH) starts in the early stage of renal insuffi ciency with still normal secretory function.It starts with the lowering of the glomerular filtration rate (GFR), combined with arterial hypertension and anemia, which mark the future LVH.

Aim
e aim of the study was to evaluate the frequency of risk factors for cardiovascular disease in patients with various stages of renal disease, with or without diabetes mellitus.

Results
It can be seen in table  and on chart , respectively, that in diabetics group there were , () of females and , () of males.Mean age was ,±, years.Chart . shows that in the non-diabetic group there were significantly more females , () than males , ().Mean age was ,±, years.
Chart  shows the distribution of causes of CRD in nondiabetic group: chronic pyelonephritis - patients (,), polycystic kidney disease -, ( patients), chronic glomerulonephritis -, ( patients), renal cancer -, ( patients), obstructive nephropathy -, ( patients), uric arthritis -, ( patients), kidney agenesis - ( patient), amyloidosis - ( patient).nephroangiosclerosis -, ( patients).Table  shows that diabetics have signifi cantly higher values (p<,) of BMI, urinary proteins, blood glucose, HbAc, BNP and IMT, and significantly lower values of EF.Mean value of homocysteine in the groups were also increased, but ranges between minimal and maximal values were much higher in diabetics group.Correlation between IMT and LDLC in diabetics is statistically significant R=,; p<,.In non-diabetics there was no significant correlation.(Chart ) There is a positive, statistically significant correlation between IMT and BNP in diabetics R=,; p<,.There was no significant correlation in non-diabetics.(Chart ) ere is negative statistical correlation between EF and BMI in both groups, more pronounced in non-diabetics R=,; p<,, than in diabetics R=,; p>,.(Chart ) It can be seen in table  that the thickness of all measured ventricular walls in diastole LA, LV, posterior wall and the septum was significantly higher in diabetics, while the ejection fraction (EF) was lower.e LV mass index was significantly higher in the diabetics group.

Discussion
Cardiovascular diseases (CVD) are the most frequent complications of type  diabetes and in more than  of diabetics constitute the cause of death (, , , ).Our study shows that patients with diabetic nephropathy had more risk factors, both traditional and non-traditional, for the development of cardiovascular complications compared with non-diabetic patients.
Increased body weight was more frequent in diabetics group, which is confi rmed by signifi cantly higher BMI values.e obesity is directly to blame for the occurrence of insulin resistance.The higher BMI further induces metabolic disturbances of lipids and blood glucose levels, which combined with hypertension, directly jeopardize the architecture and function of the heart muscle, and contribute to the development of arteriosclerosis (, , ).We have stressed that obesity and unregulated glycemia are directly refl ected on lipid metabolism disorder, which further causes the development of arteriosclerosis and changes in peripheral and blood vessels of the heart.e diabetic group had higher mean values of HDLC cholesterol, while LDLC and total cholesterol were a bit higher in the nondiabetic group, which is consistent with the data from the literature (, ).Comparing the mean cholesterol values by the groups with carotid artery intima-media thickness (IMT), we have found statistically significant positive correlation between the IMT and LDLC cholesterol R=,; p<,, in the diabetics group.Mean values of Hct and Fe in diabetics group were somewhat lower; a significant anemia syndrome has not been found in neither studied group, probably because a large number of patients were receiving substitution therapy of erythropoietin and iron supplements, as suggested in some studies ().Metabolic disorders in diabetics associated with increased body weight induce not only systemic, but also glomerular hypertension (although there are accounts of hypertension as an independent risk factor for cardiovascular occurrence), which aff ect the occurrence of microalbuminuria, proteinuria, and also represents a signifi cant cardiovascular risk (, , , , , , ).We have found higher mean values of systolic and diastolic arterial pressures in the diabetics group, and significantly higher mean value of proteinuria, which other authors also suggest (, , ).Evaluation of cardiovascular risks in the studied groups was based on ECG and echocardiography fi ndings.Risk factors inducing the development of future disorders in the heart are microangiopathies of coronary blood vessels, neuropathies of the heart nervous system, metabolic disorders and fatty degeneration of the myocardium (, , ).All of these changes occur as a consequence of high blood glucose and HbAC levels in unregulated diabetes (, , , ).ere were signifi cantly higher mean values of blood glucose and HbAC in our study, and a higher number of diabetics with left ventricular hypertrophy () and heart rhythm abnormalities (, ).Also, a higher number of diabetics had implanted electro stimulator (,), and higher number of patients had healed myocardial infarction (,,), compared to non-diabetics.e number of patients with angina pectoris and performed aortic-coronary by-passes was equal in both groups.
It is known that hyper-homocysteinemia, identified as a possible cause of cardiovascular disease, causes arteriosclerosis (), and increased heart mass (), and represents a significant risk factor of cardiovascular morbidity and mortality ().
We have found increased mean values of homocysteine in both groups, but the range between the lowest and the highest values was more signifi cant in diabetics group ().Significant arteriosclerotic changes were found in carotid arteries in , of patients, and - stenosis in one of the ACC in , of patients in diabetics group.
As a newer marker that can be used for identifi cation of cardiovascular complications is BNP (Brain Natriuretic Peptide), which is synthesized as a pre-pro BNP, mostly in myocardium of the ventricles, and whose value depends on heart contractility and load-pressure in the heart (overload).Increased serum values of the BNP is seen in patients with dysfunction of the left ventricle, correlates with the increase of pulmonary capillary pressure, with the increase in the end-diastolic pressure in the left ventricle, and ejection fraction in patients with systolic dysfunction (, , , , , ).A significantly higher value of BNP was found in patients with diabetic nephropathy.A significantly lower ejection fraction was found by echocardiography in diabetics group, and negative correlation between EF and BMI (R=,; p<,).We also found a significantly higher LV mass index in diabetics group as a sign of hypertrophy of the left ventricle (, ).

Conclusion
Signifi cantly higher values of BMI, urinary proteins, blood glucose, HbAC, BNP and IMT were found in the diabetics compared to the non-diabetics group, and signifi cantly lower values of ejection fraction (EF).ere is a signifi cant positive correlation between IMT and BNP and IMT and LDLC in diabetics group, and negative correlation between EF and BMI.A higher number of patients with increased systolic and diastolic pressures, healed myocardial infarction, rhythm abnormalities, implanted electro stimulators, and arteriosclerosis of the ACC were found in the diabetics group.Our study showed that metabolic disorders in diabetic nephropathy, caused by an uncontrolled increase of blood glucose and HbAC and other laboratory parameters, led to more frequent cardiovascular complications in the diabetics group, and that the regulation of their values was of strategic signifi cance in the treatment of nephropathy.e results of the study are to a large extent limited by the fact that the patients in both groups were treated by reference therapies respectively.

TABLE 5
TABLE 1. Distribution of patients by sex TABLE 2. Laboratory values by the groupsTable .shows that in the diabetic group there was more patients with hypertension , ( patients), myocardiopathy ,( patients), healed myocardial infarction , ( patients), implanted electro stimulator , ( patients), and rhythm disorders ( patients).Equal number of patients in both groups had angina pectoris , ( patients) and performed aortic-coronary by-passes ,( patients).Two patients from the second group (non-diabetics) had aortic aneurism surgery.Table .shows that in diabetic group there was a larger number of patients with atherosclerotic changes .Mean values of ventricular walls and the septum thickness on carotid arteries , ( patients), and ACC-ACI - stenosis had , ( patients) diabetics.