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In addition, heparan sulfate in endothelial lining of microvessel has important antithrombogenic properties, therefore its loss in chronic hyperglycemic state may contribute to the formation of microthrombi and occlusion of the small vessels of the heart. Occlusion of small vessel can lead to subendocardial ischemia further worsening systolic and diastolic myocardial function in patients with diabetes mellitus96. This is confirmed by Graca et al219 who reported that patients with T2DM and coronary atherosclerosis show a more impaired LV diastolic function than patients without coronary atherosclerosis.
6.9 MICROALBUMINURIA AND LEFT VENTRICLE DIASTOLIC DYSFUNCTION
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In the logistic analysis of 100 asymptomatic Japanese patients with T2DM, Akiyama et al221reported that the odds of having LVDD in patients with albuminuria was about 8 times more than those without albuminuria (odds ratio [OR] 7.95, 95% confidence interval{CI}1.74-21.6, P=0.005).
In contrast, in the work of Alwis et al14 on diabetic patients of Asian descent, it was demonstrated that out of twenty-eight cases of T2DM without any cardiovascular disease, 73.7% of those without microalbuminuria and 66.7% of those with microalbuminuria had LVDD, suggesting no significant association of microalbuminuria to LVDD.
Likewise, Yildirimturk et al222 found in their study on 38 asymptomatic diabetics without MCA and 12 with MCA that echocardiographic findings showed no significant differences in left ventricular systolic and diastolic functions between patients with or without MCA (p>0.05).
Similar finding was also reported by Cakir et al223 in their study of 36 normotensive diabetics with or without microalbuminuria.
Romano et al211 also found among 54 caucasians with uncontrolled T2DM, that frequency of MCA was equal in both groups with or without LVDD (29%). Even though the four studies mentioned above used quantitative method to test for urinary albumin excretion, but the relatively smaller sample sizes may probably be the reason for lack of significant difference in diastolic function between diabetic patients with or without MCA.
In the present study, the univariate model showed a strong direct association of LVDD with microalbuminuria (OR 3.58, 95% CI 1.99-6.82, p<0.001), as well as age, (OR 1.1, 95% CI 1.04-1.17, P<0.001). Results from this study and previous one220 highlight a strong association between microalbuminuria and left ventricular diastolic dysfunction among normotensive
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patients with T2DM. Previous studies have also shown that albuminuria is an independent predictor of LVDD96.
In multivariate model, only age remained as an independent predictor of LVDD (OR 1.10, 95% CI 1.03-1.17,P< 0.003) after controlling for other confounders including microalbuminuria. It is commonly believed that grade 1 diastolic dysfunction in patients above 65 years may simply represent relaxation abnormality associated with normal aging process, however patients younger than 65 years may represent impaired relaxation due to other conditions that may be a precursor to more advanced diastolic impairment if not treated.
In the present study, subjects older than 65 years were excluded, in addition the negative prevalence in the control group of grade 2 and 3 LVDD and the fact that pseudonormal and restrictive left ventricular filling patterns are usually pathological phenomenons and not part of the aging process217. Therefore the higher proportion of LVDD seen in the diabetic groups is linked not only to aging but also diabetes mellitus with or without MCA.
However, Magnusson et al11 found age, as well as albumin excretion rate (AER) and systolic blood pressure to be independent predictors of LVDD. The failure of microalbuminuria to be an independent predictor in this study may be because of the semiquantitative method used to test for MCA and the relatively small sample size in the present study. Inclusion of both micro- and macroalbuminuria as albuminuria would have increased the chances of detecting albuminuria as an independent predictor of LVDD as shown in other studies96
But the aim of this study, was to see if microalbuminuria in normotensive T2DM could identify when to start preventive measures to check deterioration not only in renal but also in cardiac functions in T2DM patients. This therefore suggests that although the association between
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MCA (detected by semi-quantitative method) and LVDD in normotensive patients with T2DM is weak, it is still stronger than the association of T2DM without albuminuria with LVDD.
It is important to emphasize that microalbuminuria has been shown as a strong and independent predictor of cardiovascular disease not only in form of cardiac structural abnormalities and dysfunction but also heart failure, ischemic heart disease, cerebrovascular disease and kidney failure in patients with or without diabetes mellitus224,225.
Java et al226 reported in their study of 35 African-American patient with persistent microalbuminuria and 15 matched patient whose microalbuminuira has resolved following treatment with ACEI, that MCA is an independent predictor of abnormal endothelial functions such as impaired flow mediated dilatation and nitroglycerin dependent dilatation which are features of cardiovascular damage in diabetes mellitus.
In addition, microalbuminuria status, hypertension, dyslipidemia and smoking have been found to be significantly more frequent in asymptomatic diabetic patient with ischemic cardiac exercise tolerance test (ETT) when compared with those with normal ETT227.
This is supported by previous argument that microalbuminuria reflects an increase in renal and systemic transvascular leakiness which is perhaps due to the low vessel wall content of heparan sulfate96. The resultant increased deposition of collagen, cholesterol and advanced glycated end products in the myocardium of human hearts have also been thought to cause increase end-diastolic myocardial stiffness, impair left ventricle relaxation during diastole as well as alter normal systolic function96.
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