Diabetes mellitus is a major risk factor for cardiovascular morbidity and mortality. This condition increases the risk of developing coronary, cerebrovascular, and peripheral arterial disease fourfold. Endothelial dysfunction is a major contributor to the pathogenesis of vascular disease in diabetes mellitus patients and has recently received increased attention. In this review article, some recent developments that could improve the knowledge of diabetes-induced endothelial dysfunction are discussed.

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Endothelial dysfunction is a key event in the development of vascular disease, and it precedes clinically obvious vascular pathology. Abnormal activation of the RhoA/Rho kinase (ROCK) pathway has been found to elevate vascular tone through unbalancing the production of vasodilating and vasoconstricting substances. Inhibition of the RhoA/ROCK pathway can prevent endothelial dysfunction in a variety of pathological conditions. This review, based on recent molecular, cellular, and animal studies, focuses on the current understanding of the ROCK pathway and its roles in endothelial dysfunction.

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Chronic stable angina is a clinical expression of myocardial ischemia associated with fixed atherosclerotic coronary stenosis, which prevents the adaptation of coronary circulation resulting in an increased oxygen requirement. We recommend that once the diagnosis of chronic stable angina is made, first every patient should be offered the optimal medical therapy, including ACE inhibitors, beta-blockers, statins, and nitrates. If the patients' symptoms are not controlled in spite of these drugs being used in maximum tolerated dosages, then these patients should be subjected to coronary angiography. If a patient shows a single- or double-vessel disease, then PCI should be offered. On the contrary, if the coronary angiogram shows a triple-vessel disease and left main disease, then one has to look for comorbidities that put the patient at a higher risk of CABG and the patient should be treated with PCI. Other patients with left main and triple-vessel disease having diabetes and left ventricular dysfunction should go directly for surgical revascularization. Overall, health related quality of life ( HRQoL) is similar in both PCI and CABG.

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Atherosclerosis is the leading cause of death in developed countries. High density lipoproteins (HDL) cholesterol level correlates inversely with the risk of cardiovascular diseases. Thus, HDL has obtained lots of interest for drug development. In this review, we summarized the mechanisms for the antiatherogenic function of HDL, current HDL-based drugs in clinical use and the future direction for HDL-based therapy development.

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Background: Several studies hinted about the clustering of risk variables of the metabolic syndrome (MS) and suggested that the underlying genetic polymorphisms could be responsible for the increasing incidence of coronary heart disease (CHD) in people of Indian origin. Therefore, identification of the components of the MS along with the genetic factors could be one of the aspects to make an attempt to prevent the increasing incidence of CHD. Materials and Methods: Principal component factor analysis (PCFA) was undertaken to identify the components or factors of the MS among the adult (≥30 years) Asian Indians living in and around Calcutta, India. The study comprised 350 adult Asian Indians. Anthropometric measurements were taken, and lipid profiles, blood pressure and fasting blood glucose were measured for each participant. Two genetic polymorphisms, namely, angiotensin converting enzyme (ACE) gene polymorphism (insertion/deletion [I/D]) or ACE (I/D) and apolipoproteinE (Hha I) were also studied. Results: PCFA revealed 3 factors that cumulatively explained 65.39% of the observed variance of the MS by measured variables. The 3 factors identified were lipids and lipoprotein (Factor 1), centripetal fat and blood pressure (Factor 2), and ACE (I/D) polymorphism with blood pressure (Factor 3). Moreover, the first 2 factors, that is, lipids, lipoprotein, centripetal fat, and blood pressures cumulatively explained ~46% (45.94%) of the observed variance of MS in this population. Conclusions: Since more than 1 factor was identified for the MS phenotype, more than 1 physiogenetic mechanism could be accounted for MS in the Asian Indian population.

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Background: Coronary artery disease (CAD) is the most common cause of sudden death, none and death of men and women over 20 years of age. The aim of the study was to know if there is any linear correlation between oxidants and abnormal lipid profile parameters in CAD. Materials and Methods: The present study includes 42 known CAD cases (age = 41-75 years) and 33 age- and sex-matched healthy controls. Malondialdehyde ( MDA), total cholesterol, high-density lipoprotein (HDL) cholesterol, and triacylglyceride were measured and low-density lipoprotein (LDL) cholesterol was calculated in both cases and controls, respectively. Results: MDA was significantly increased in cases than controls (P = 0.0000001). Total cholesterol was high in cases than controls (P = 0.0000001). HDL cholesterol was significantly decreased in cases than controls (P = 0.0000001). LDL cholesterol was high in cases than controls (P = 0.0000001). Triacylglyceride was high in cases than controls (P = 0.0000001). Insignificant positive correlation were observed between MDA and total cholesterol (r = 0.258), between MDA and LDL cholesterol (r = 0.199), and between MDA and HDL cholesterol (r = 0.134). Negative correlation was observed between MDA and triacylglyceride (r = -0.314). Conclusion: Increased oxidative stress and abnormal lipid profile were observed in CAD cases. Our study showed that statistically significant linear relationship could not be established between increased oxidative stress and abnormal lipid profile parameters, suggesting that increased oxidative stress and abnormal lipid profile are two independent risk factors in the pathomechanism of atherogenesis.

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Background: The current study aims at assessment of heart rate variability among children and adolescents with childhood anxiety disorder, using the case-control design. Materials and Methods: The study was carried out at a tertiary care multispecialty hospital. It included 34 children and adolescents with diagnosis of childhood anxiety disorder, in the age range of eight to eighteen years, and 30 age- and sex-matched healthy controls. Heart-rate variability was studied using the standard protocol. Results: Significantly reduced variability of the heart rate was observed in both the time as well as frequency domains in the disorder group as compared to the control group. These findings indicate decreases in the sympathetic and parasympathetic activity in the disorder group, thus representing diminished physiological variability at rest. Conclusions: The notion of autonomic inflexibility, as seen in the current study, has important implications for stability in biological systems. The loss of variability in the physiological systems in general, and in the cardiovascular system in particular, has an association with a number of diseases and dysfunctions.

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Diabetic retinopathy (DR) is one of the most common complications of diabetes and is a leading cause of blindness in people of the working age in Western countries. A major pathology of DR is microvascular complications such as non-perfused vessels, microaneurysms, dot/blot hemorrhages, cotton-wool spots, venous beading, vascular loops, vascular leakage and neovascularization. Multiple mechanisms are involved in these alternations. This review will focus on the role of inflammation in diabetic retinal microvascular complications and discuss the potential therapies by targeting inflammation.

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Background: Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs, useful for control of diabetes mellitus type two and it may exert anti inflammatory activity, by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway. Repaglinide is a new hypoglycemic agent, and a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has favorable effects on the parameters of antioxidative balance. Objectives: The objective of the present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with the inflammatory and oxidative pathways. Materials and Methods: Twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits were fed with 1% cholesterol enriched diet. Group III rabbits were fed with 1% cholesterol enriched diet together with Glimepiride (0.1 mg/kg once daily before morning feed). Group IV rabbits were fed with 1% cholesterol enriched diet together with Repaglinide (0.3 mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), high sensitive C - reactive protein (hsCRP), Interleukin - 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α) levels. At the end of 10 weeks, the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness. Results: Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group (P < 0.05). Also, they significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P < 0.05), and they helped to restore the aortic GSH levels (P < 0.05). Conclusions: Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbits by interfering with the inflammatory and oxidative pathways without affecting lipid parameters.

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Background and Aim: Rheumatic fever is still a common cause of acquired heart disease in children and young adult in many developing countries. The aim was to investigate the role of myocardial involvement in the hemodynamic changes in patients with acute rheumatic fever using cardiac troponin assay and echocardiography. Design: A prospective cohort study was designed. Patients and Methods: Thirty-four children with acute rheumatic fever, 20 with carditis, and 14 without carditis. Level of cardiac troponin T (cTnT) and echocardiographic measurement of left ventricular function were the main outcome measure. Results: The level of cardiac troponin in children with carditis was 0.051 ± 0.01 ng/dL, and it was 0.039 ± 0.02 ng/dL in those without carditis. The difference is not significant. In addition, there was no significant difference between the children with carditis and those without carditis regarding left ventricular ejection and shortening fractions. Conclusion: There are no significant echocardiographic measurements abnormalities or cTnT levels elevation suggesting clinically relevant hemodynamic abnormalities due to myocardial involvement during acute rheumatic fever.

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Background: Myocardial perfusion imaging (MPI) is a powerful diagnostic and prognostic tool for evaluating coronary artery disease (CAD). Several studies have shown Type 2 diabetics are at increased risk for having CAD. In addition, insulin resistance is generally considered to be of major importance in the pathophysiology of Type 2 diabetes mellitus. However, the area of screening prediabetics for CAD remains unclear. Given that glucose intolerance and insulin resistance precede the development of overt diabetes, these factors would be associated with CAD. Aim: This study was designed to evaluate the state of myocardial perfusion in prediabetic adults detected by single photon emission computed tomography (SPECT) in relation to insulin resistance. Patients and Methods: A descriptive study was performed. Out of 113 consecutive prediabetic adults, 32 had insulin resistance (Group A) and 81 had insulin sensitivity (Group B). All were subjected to full medical history and clinical examination including blood pressure, waist circumference, and body mass index. Biochemical studies including lipids profile, fasting blood glucose, and homeostasis model assessments (HOMA) test. Exercise treadmill technetium (99mTC) sestamibi SPECT scintigraphy were done for assessment of myocardial perfusion assessed by summed difference score as well as occurrence of transient left ventricular dilatation. Results: Significant increase in summed difference score as well as transient left ventricular dilatation was observed in Group A than Group B. It is correlated with insulin resistance, and the correlation appears to be independent of glucose tolerance status and obesity. Similar correlations were observed with age, triglycerides, and waist circumference. Conclusion: Prediabetics have myocardial perfusion defects which represent a pattern of cardiovascular risk. These are predominantly observed in prediabetics with increased HOMA IR and visceral obesity independent of glucose levels.

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Objective: To study the role of multidetector computed tomography (MDCT) in evaluating various complications following endovascular stenting of aortic aneurysms. Materials and Methods: Over a period of 2 years (June 2005 to June 2007), 50 patients with aortic aneurysm on computed tomography (CT) angiogram were prospectively studied. Images were acquired on a 64 slice multidetector row CT scanner (GE-LightSpeed VCT) after intravenous administration of nonionic iodinated contrast. Nineteen patients underwent endovascular stent-graft repair based on their medical and surgical risk factors. Stent-graft related complications were recorded by CT angiography and analyzed using descriptive statistics. Results: Most common complication related to the endovascular stent-graft placement was endoleak (44.4%), followed by puncture site hematoma (27.8%), thrombotic occlusion of a limb of the bifurcated stent graft, kinking of the stent-graft, and difficult catheterization with intimal tear in the common iliac artery were 5.6% each. Poststent diameter of the aneurysm was an important predictor of endoleaks. All the patients with either increase or no change in the aneurysm size had endoleaks. Conclusion: MDCT angiography is an important modality in identifying, describing, and following up the various complications following endovascular repair of aortic aneurysms, endoleaks being the most common complication. Decrease in the poststent diameter of the aneurysm suggested a good outcome.

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Background: Gene-environment interaction is an important aspect in the development of coronary artery disease (CAD). The mutation (677C-T) of methylenetetrahydrofolate reductase (MTHFR) gene results in a decrease of the enzyme activity that leads to mild hyperhomocysteinemia. Elevated plasma level of homocysteine has been recognized as an independent risk factor for cardiovascular disease. A case-control study was designed to assess whether the prevalence of some MTHFR gene polymorphisms have any role in the development of CAD. Materials and Methods: The study included unrelated 217 cases with CAD and 255 healthy controls. DNA was extracted from peripheral blood. MTHFR genotypes were identified by seeing the presence or absence of 677C→T mutation obtained by PCR followed by Hinf1 restriction digestion. Multiple logistic regression analysis was carried out to find association between studied genotypes and lifestyle as well as biochemical risk factors. Results: The T allele was found to be associated with the disease. Significant associations were found with smoking, hypertension, diabetes, and family history of CAD. Conclusion: The results indicate that MTHFR 677C-T polymorphism has significant association with CADs in the population of eastern India.

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Background: No study has been undertaken on people of Asian Indian origin to investigate the age and sex variation in the prevalence of cardiovascular disease (CVD) risk factors. Objectives: To investigate the age and sex variation in the prevalence of CVD risk factors among the people of Asian Indian origin. Materials and Methods: A total of 682 (302 males and 380 females) participants aged 25-85 years took part in the study. The subjects were categorized into 4 groups, namely, Group I (25-34 years), Group II (35-44 years), Group III (45-54 years), and Group IV (55 years and above). Height, weight, and the circumferences of minimum waist (MWC) and maximum hip were collected using standard techniques. Waist-hip ratio (WHR) was then calculated. Percentage of body fat (%BF) and body mass index (BMI) were measured using an Omron body fat analyzer. Left arm systolic (SBP) and diastolic (DBP) blood pressure were taken from each participant with the help of an Omron MI digital electronic blood/pulse monitor. Metabolic profiles, namely, total cholesterol (TC), triglyceride (TG), high (HDL), low (LDL), very low-density lipoprotein (VLDL), and fasting blood glucose (FBG) were also measured using an autoanalyzer. Results: One-way analysis of variance revealed significant differences for age, BMI, MWC, WHR, SBP, DBP, TC, TG, LDL, VLDL, and TC:HDL and TG:HDL ratios across the groups. It was observed that there were significant sex-specific group differences (male [χ² (12)] =29.22, P < 0.01 and female [χ² (12)] =56.69, P < 0.001) for obesity, high BP, high TC, high TG, and high FBG. But no significant group-specific sex difference was evident for either of the risk factors, except for Group IV. Conclusion: Age irrespective of sex modulates CVD risk factors and warranted prevention as early as middle age.

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