Artery Disease Diabetes Mellitus Research Articles

Donepezil is emerging as a potential therapeutic treatment in improving endothelial barrier function to prevent and treat coronary artery disease in Diabetes Mellitus.

Abstract Current treatments have shown limited success in reversing DM induced vascular endothelial barrier dysfunction. Vascular endothelium forms the inner most lining of the blood vessels, regulates variety of biological processes such as angiogenesis, wound healing and host defense mechanisms. During inflammatory conditions, such as diabetes mellitus and myocardial infarction endothelial cell-cell junctions start to disrupt because of the internalization of the junctional proteins, such as vascular endothelial (VE) cadherin. This leads to the formation of minute inter-endothelial gaps, and the infiltration of protein-rich fluid and immune cells in the interstitial space. If remains unchecked, the persistent buildup of edema underlying the endothelial lining sets the stage for the serious life-threatening complications. Therefore, we hypothesized that the donepezil prevents high glucose-induced endothelial barrier dysfunction by preventing the destabilization of junctional proteins. We investigated the potential protective role of Donepezil in high glucose induced increase in human coronary artery endothelial (HCAE) permeability and wound healing process. Wound healing assay was performed by employing electric signals to both wound and monitor the healing process in endothelial monolayer. To investigate the signaling mechanism involved in the protection offered by Donepezil, we found that Donepezil prevented loss of VE-cadherin in endothelial junctions, and abrogated stress fiber formation in endothelial cell exposed to high-glucose solution. In conclusion, our study shows that Donepezil maintained endothelial barrier function and improved wound healing process in endothelial cells exposed to high glucose. Chicago State University CTRE grant to Professor Nadeem Fazal, MD, PhD

Association between selective serotonin reuptake inhibitor and risk of peripheral artery disease in diabetes mellitus: Propensity score matching and landmark analysis.

An increasing number of studies have demonstrated the bidirectional hemostatic effect of selective serotonin reuptake inhibitors (SSRIs) on the risk of cerebrovascular and cardiovascular diseases. However, no previous study has focused on the relationship between SSRI and the risk of peripheral artery disease (PAD) in diabetes mellitus (DM). We sought to evaluate the association between SSRIs and the PAD risk in individuals with DM.We conducted a retrospective, population-based cohort study using data from the Longitudinal Health Insurance Database from 1999 to 2010 in Taiwan. A total of 5049 DM patients were included and divided into 2 groups: DM with SSRI users and DM with SSRI non-users. Propensity score matching and 1-year landmark analysis were used for our study design. Stratified Cox proportional hazard regressions were used to analyze the hazard ratio of the PAD risk in certain subgroups.DM with SSRI users did not affect the PAD risk compared to DM with SSRI non-users. These findings were consistent with all sensitivity analyses (i.e., age, sex, SSRI doses, antithrombotic medication use, and medical and psychiatric comorbidities).In this study, we found that there was no significant difference of PAD risk between DM with SSRI users and DM with SSRI non-users. DM with SSRI user did not affect PAD risk across any SSRI dose, age, sex, antithrombotic medications, and multiple comorbidities in the subgroup analysis.

Ankle Peak Systolic Flow Velocity (PSV) with Coronary Artery Disease in Diabetes Mellitus

Introduction: Ankle peak systolic flow velocity can measure peripheral arterial blood flow which can predict extent of peripheral arterial disease. Atherosclerosis is more common in patients with diabetes mellitus and can affect simultaneously coronary circulation and peripheral circulation.
 Aims and Objectives: The primary objective of the study was to determine the occurrence of peripheral vascular disease by ankle Peak Systolic Velocity (PSV) in patients admitted for coronary artery disease with diabetes mellitus .The secondary objective was to see the association between the ankle Peak Systolic Flow Velocity (PSV) with the extent of abnormality of coronary angiogram in diabetic patients.
 Materials and Methods: All patients admitted in the hospital with coronary artery disease with diabetes mellitus in whom coronary angiogram was done were included in the study over a period of one year Presence of significant vessel disease CAD was defined as at least >70 % stenosis at one or more major coronary arteries (left anterior descending, left circumflex and right coronary artery). Ankle Peak Systolic Velocity (PSV) was measured in all patients by the Duplex method. The peak systolic velocities in the distal posterior tibial artery and the distal anterior tibial artery was measured and the average peak systolic velocities within three cardiac cycles6 was recorded by the radiologist. The ankle peak systolic flow above 40cm/s was considered as good flow in the lower limb extremity [7]. The data was analysed using SPSS version 17.0 software and mean and standard deviation was used .
 Results: Out of the cases studied 24 patients (80%) were males and 6 patients (20%) were females. All the Coronary angiograms was classified to single 13(43.3%), double 8(26.7%) and triple 9 (30%) vessel disease by the cardiologist. Out of the 13 patients with single vessel disease 3 patients had < 40 cm/s flow in the right anterior tibial artery and 10 patients had >40 cm/s flow in the right tibial artery indicating good perfusion.Out of the 8 patients with double vessel disease 4 patients had flow <40 cm/s and 4 patients had flow >40 cm/s. In triple vessel disease category 5 patients had flow <40 cm/s and 4 patients had flow>40cm/s. The p value was 0.2 was not significant and the chi square was 2.79 Similar results were obtained while compared with left ankle peak systolic flow velocity.
 Conclusion: In this study patients with single vessel disease have higher ankle peak systolic velocity though statistically not significant. Lower ankle peak systolic flow velocity corroborates with peripheral arterial disease [12] and is seen in patients with coronary artery disease [13].

Peripheral Artery Disease in Diabetes Mellitus: Focus on Novel Treatment Options.

Diabetes mellitus (DM) and peripheral artery disease (PAD) are two clinical entities closely associated. They share many pathophysiological pathways such as inflammation, endothelial dysfunction, oxidative stress and pro-coagulative unbalance. Emerging data focusing on agents targeting these pathways may be promising. Moreover, due to the increased cardiovascular risk, there is a growing interest in cardiovascular and "pleiotropic" effects of novel glucose lowering drugs. This review summarizes the main clinical features of PAD in patients, the diagnostic process and current medical/interventional approaches, ranging from "classical treatment" to novel agents.

Fragmented QRS complexes are associated with left ventricular dysfunction in patients with type-2 diabetes mellitus: a two-dimensional speckle tracking echocardiography study

Background: Heart failure may develop independently of coronary artery disease in diabetes mellitus (DM) patients. Fragmented QRS (fQRS) is a marker of myocardial fibrosis or scar tissue and is related to an increase in cardiovascular adverse events. In this study, we examined the utility of speckle tracking echocardiography (STE) in assessing LV function in DM patients with fQRS. Methods and Results: The current study included 178 consecutive patients diagnosed with type-2 DM. The patients included were separated into two groups: those with (n = 50) and without (n = 128) fQRS. The two groups were compared by obtaining LV strain values with STE. Statistically significant differences were also identified between fQRS(−) and fQRS (+) groups with respect to Lv-GLS (p < .001), maxLAVI (p = .020), minLAVI (p < .001), E velocity (p < .001), Em velocity (0.002), E/Em ratio (<0.001) SRe (p < .001), SRe/SRa ratio (p < .001), SRivr (p < .001) and E/SRivr ratio (p < .001). In the multiple linear regression analysis, fQRS (β = −2.077, p = .002) and DM duration (β = −0.216, p = .021) were identified as independent predictors of Lv-GLS. However, fQRS (β = 4.557, p = .001) and minLAVI (β = −2.198, p = .031) were also found to be independent predictors of E/SRivr. We also performed multiple logistic regression analysis and identified Lv-GLS (β = −0.557, p = .001), minLAVI (β = −0.769, p = .001), E/Em ratio (β = 0.650, p = .001) and E/SRivr (β = 0.105, p = .001) as independent predictors of fQRS. Conclusıons: The results of this study revealed that subclinical LV dysfunction was more common in diabetic patients with fQRS. Therefore, determination of fQRS could be an indicator of the diabetic CMP in patients with DM.

Role of Differential Signaling Pathways and Oxidative Stress in Diabetic Cardiomyopathy

Diabetes mellitus increases the risk of heart failure independently of underlying coronary artery disease, and many believe that diabetes leads to cardiomyopathy. The underlying pathogenesis is partially understood. Several factors may contribute to the development of cardiac dysfunction in the absence of coronary artery disease in diabetes mellitus. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Hyperglycemia-induced oxidative stress is a major risk factor for the development of micro-vascular pathogenesis in the diabetic myocardium, which results in myocardial cell death, hypertrophy, fibrosis, abnormalities of calcium homeostasis and endothelial dysfunction. Diabetes-mediated biochemical changes show cross-interaction and complex interplay culminating in the activation of several intracellular signaling molecules. Diabetic cardiomyopathy is characterized by morphologic and structural changes in the myocardium and coronary vasculature mediated by the activation of various signaling pathways. This review focuses on the oxidative stress and signaling pathways in the pathogenesis of the cardiovascular complications of diabetes, which underlie the development and progression of diabetic cardiomyopathy.

Revascularization for coronary artery disease in diabetes mellitus: Angioplasty, stents and coronary artery bypass grafting

Patients with diabetes mellitus (DM) are prone to a diffuse and rapidly progressive form of atherosclerosis, which increases their likelihood of requiring revascularization. However, the unique pathophysiology of atherosclerosis in patients with DM modifies the response to arterial injury, with profound clinical consequences for patients undergoing percutaneous coronary intervention (PCI). Multiple studies have shown that DM is a strong risk factor for restenosis following successful balloon angioplasty or coronary stenting, with greater need for repeat revascularization and inferior clinical outcomes. Early data suggest that drug eluting stents reduce restenosis rates and the need for repeat revascularization irrespective of the diabetic state and with no significant reduction in hard clinical endpoints such as myocardial infarction and mortality. For many patients with 1- or 2-vessel coronary artery disease, there is little prognostic benefit from any intervention over optimal medical therapy. PCI with drug-eluting or bare metal stents is appropriate for patients who remain symptomatic with medical therapy. However, selection of the optimal myocardial revascularization strategy for patients with DM and multivessel coronary artery disease is crucial. Randomized trials comparing multivessel PCI with balloon angioplasty or bare metal stents to coronary artery bypass grafting (CABG) consistently demonstrated the superiority of CABG in patients with treated DM. In the setting of diabetes CABG had greater survival, fewer recurrent infarctions or need for re-intervention. Limited data suggests that CABG is superior to multivessel PCI even when drug-eluting stents are used. Several ongoing randomized trials are evaluating the long-term comparative efficacy of PCI with drug-eluting stents and CABG in patients with DM. Only further study will continue to unravel the mechanisms at play and optimal therapy in the face of the profoundly virulent atherosclerotic potential that accompanies diabetes mellitus.

Revaskularisation der koronaren Herzerkrankung bei Diabetes mellitus

Coronary artery disease in diabetes mellitus (DM) is still associated with a poor prognosis. Especially percutaneous coronary interventions (PCI) have a higher rate of complications and restenosis, so that surgical revascularization is usually favoured in DM. The development of drug-eluting stents has improved the results of PCI significantly, however, there are still not enough prospective data comparing them to bypass surgery. The present paper summarizes the current state of coronary revascularization.

Diabetic Cardiomyopathy Revisited

Diabetes mellitus increases the risk of heart failure independently of underlying coronary artery disease, and many believe that diabetes leads to cardiomyopathy. The underlying pathogenesis is partially understood. Several factors may contribute to the development of cardiac dysfunction in the absence of coronary artery disease in diabetes mellitus. This review discusses the latest findings in diabetic humans and in animal models and reviews emerging new mechanisms that may be involved in the development and progression of cardiac dysfunction in diabetes.

Antibodies to oxidized LDL and LDL-containing immune complexes as risk factors for coronary artery disease in diabetes mellitus.

Several groups have published results from clinical studies supporting the involvement of anti-modified LDL antibodies as risk factors for the initiation or progression of cardiovascular disease. However, the data published so far are judged inconclusive because of several contradictory observations concerning the correlation between clinical evidence of arteriosclerosis and the levels of antibodies to oxidized LDL (oxLDL Ab). We have previously reported that oxLDL Ab exist both in free form and as antigen-antibody complexes (LDL-IC) in patients with insulin-dependent diabetes mellitus (IDDM). The presence of LDL-IC in IDDM patients has important implications: it may interfere with the assay of oxLDL antibodies and the levels of LDL-IC may correlate better with the development of arteriosclerosis than the levels of free oxLDL antibodies. To clarify these questions baseline samples collected from 49 IDDM patients, who subsequently developed coronary artery disease (CAD) during an 8-year follow-up period, were compared to baseline samples from 49 age-, sex-, and duration-matched control IDDM subjects who remained free of clinical CAD during an identical follow-up period. The levels of free oxLDL antibody were significantly lower in the patients who developed CAD. The same patients had significantly higher concentrations of total cholesterol, apolipoprotein B, and IgA in immune complex-enriched polyethylene glycol (PEG) precipitates. The concentration of IgG was also higher in PEG precipitates from patients who developed CAD, but did not reach statistical significance. This indicates that patients who develop CAD had higher levels of circulating LDL-IC, a fact that could not be deduced from the measurement of free oxLDL antibody concentrations. A linear regression analysis of the correlation between the concentrations of total cholesterol in PEG precipitates, taken as a surrogate measurement of PEG-precipitated oxLDL-IC, and the concentration of free oxLDL antibody in serum showed a statistically significant negative correlation (r = -0.229, P = 0. 024). Our results support the conclusion that oxLDL-IC may be a risk factor for the development of macrovascular disease in IDDM patients. We also have demonstrated that circulating oxLDL-IC interfere with the assay of free oxLDL antibodies.

An atherogenic midband lipoprotein: a risk factor for coronary artery disease in diabetes mellitus with hyperlipidemia

On polyacrylamide gel (PAG) disc electrophoresis of serum lipoproteins, the band(s) which migrates between pre β- and β-lipoproteins was more frequently observed in hyperlipidemics with diabetes mellitus (73%), than in those without diabetes mellitus (37%) ( P<0.01). Those bands were seen at three positions between pre β- and β-lipoproteins. A higher incidence of coronary artery disease (CAD) was observed in patients with midband as a shoulder of β-lipoproteins (44%), than in those without midband (11%) ( P<0.05) after the matching of other risk factors. These results suggest that midband as a shoulder of β-lipoproteins may be a risk factor for CAD in diabetes mellitus with hyperlipidemia.

Evolving natural history of coronary artery disease in diabetes mellitus

White diabetic patients are at high risk of developing coronary artery disease (CAD). The natural history of CAD in insulin-dependent (ID) and noninsulin-dependent (NID) diabetes mellitus (DM) is reviewed to gain insight into the mechanisms responsible for the development of premature or accelerated atherosclerosis in diabetic patients. In both IDDM and NIDDM, the risk of CAD increases with lengthening duration of diabetes; the risk, however, does not grow as a constant multiple of the nondiabetic risk of CAD, suggesting that the cumulative exposure to diabetes plays a significant role as a risk factor for CAD only in a subset of patients. This is consistent with the hypothesis that the diabetic milieu has an impact on the progression of atherosclerotic lesions but not on their initiation. This hypothesis is corroborated further by the observation that CAD does not occur in diabetic patients in populations with a low risk of CAD among nondiabetic patients. The component of the diabetic milieu responsible for promotion of atherosclerotic lesions is unknown. There is evidence, however, of a direct or indirect role of hyperinsulinemia in this process.

Atherosclerosis of Coronary and Renal Artery Disease in Diabetes Mellitus

Atherosclerosis is a systemic disease. Although asymmetries in arterial involvement in atherosclerosis may occur, disease usually proceeds in parallel in various organ systems. From a clinical perspective, knowing the prevalence of renal artery involvement in patients with the evidence of atherosclerosis in other organs is important because this knowledge may be incorporated into diagnostic algorithms. This study was aimed to determine the presence of atherosclerotic renal artery disease in diabetes mellitus with coronary artery disease. A total of 173 coronary artery disease patients were purposively selected for the study .Fasting blood sugar level was estimated. Coronary angiograms were performed by standard percutaneous femoral artery cannulation (Judkins Technique).Selective right and left judkins catheter and hand dye injection were used for opacification of renal arteries. Of the 173 study subjects, 143 (diabetic 73) were male and 22 (diabetic 15) were female. Among the diabetic 15 patients had renal artery stenosis and only 7 patients had renal artery stenosis in the non diabetic group. Strength of link between significant renal artery stenosis were strongly correlated (r=0.233, and p, 0.001). Knowledge on the clinical evolution and on the cardiovascular squeal of atherosclerotic renal disease has made substantial progress in recent years. Atherosclerotic renal artery disease is present in significant proportion of diabetic patients undergoing cardiac catheterization for suspected coronary artery disease in comparisons to their non diabetic counter parts. Keywords : Atherosclerosis; Diabetes mellitis; renal artery stenosis DOI: 10.3329/uhj.v5i2.4556 University Heart Journal Vol.5(2) July 2009 pp.63-65

THE FAMILIAL OCCURRENCE OF HYPERTENSION AND CORONARY ARTERY DISEASE, WITH OBSERVATIONS CONCERNING OBESITY AND DIABETES

Excerpt I. INTRODUCTION It is commonly thought that certain families are afflicted with high blood pressure, strokes and heart attacks with unwarranted frequency and to a severe degree. Sudden deat...

Incidence and clinical significance of coronary artery disease in diabetes mellitus: Stearns, S., Schlesinger, M. J., and Rudy, A.: Arch. Int. Med. 80:463 (Oct.), 1947

Incidence and clinical significance of coronary artery disease in diabetes mellitus: Stearns, S., Schlesinger, M. J., and Rudy, A.: Arch. Int. Med. 80:463 (Oct.), 1947