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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension contributes to the progression of renal disease by accelerating structural changes in the kidney, leading to a progressive decline in glomerular filtration rate. Hypertension and microvascular changes can create a vicious circle, leading to further renal damage and increases in blood pressure. Prevention of renal damage is a priority, especially in the growing number of patients with diabetic hypertension. Angiotensin receptor blocking drugs and ACE inhibitors have been shown to display renoprotective effects, and ACE inhibitors reduce the risk of microalbuminuria, the initial step in renal disease in diabetes. Impressive results have been obtained with a low-dose combination of the ACE-inhibitor perindopril and the diuretic indapamide, which not only gave superior reductions in blood pressure to enalapril, but also a 24% greater reduction in albumin excretion. Perindopril/indapamide also showed a trend towards reducing cardiovascular events. There is evidence from animal studies that this combination protects both renal structure and function.
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PMID:[Vascular impact of anti-hypertensive treatment and renal protection]. 1619 49

The role of angiotensin-converting enzyme (ACE) inhibitors in diabetic patients with preserved ventricular function is uncertain. Tissue ACE inhibitors have been defined by increased lipophilicity and structural characteristics that result in greater tissue-specific ACE binding when compared with plasma ACE inhibitors. A Bayesian meta-analysis of randomized trials was conducted to evaluate tissue ACE inhibitors in prevention of cardiovascular disease among patients with diabetes mellitus and preserved left ventricular function. Four trials were selected that evaluated 2 different ACE inhibitors and included 10,328 patients (43,517 patient-years). The Perindopril Substudy in Coronary Artery Disease and Diabetes (PERSUADE) and the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) compared the effects of perindopril vs a placebo, and the Heart Outcomes Prevention Evaluation (HOPE) and the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study investigated the impact of ramipril vs a placebo. Bayesian meta-analysis of sequential trials and sensitivity analysis of therapeutic response were subsequently computed. Bayesian meta-analysis determined reduced risk of cardiovascular mortality (PB=.991), myocardial infarction (PB=.999), and the need for invasive coronary revascularization (PB=.995) when compared with placebo. Total mortality was also decreased (PB=.967), while the risk of stroke (PB=.907) and hospitalization for heart failure (PB=.923) were impacted. Bayesian meta-analysis of randomized trials suggests that tissue ACE inhibitors decrease the probability that diabetic patients with preserved left ventricular function will experience myocardial infarctions and cardiovascular death and reduce overall mortality.
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PMID:Bayesian meta-analysis of tissue angiotensin-converting enzyme inhibitors for reduction of adverse cardiovascular events in patients with diabetes mellitus and preserved left ventricular function. 1832 70

The year 2008 was rich in teachings and suspense in diabetology. Past studies, i.e. United Kingdom Prospective Diabetes Study (UKPDS) in type 2 diabetic patients and Diabetes Control and Complications Trial (DCCT) in type 1 diabetic patients, have shown that in the short term, intensive treatment reduces the incidence of microvascular complications linked to diabetes and in the long term that of both microvascular and macrovascular ones. The in-the-raw conclusions of the recent Action to Control Cardiovascular risk in Diabetes (ACCORD) study note an increase in mortality in type 2 diabetic patients treated intensively, while the Action in Diabetes and Vascular disease, Perindopril and Indapamide Controlled Evaluation (ADVANCE) study evidences a reduction in microvascular complications and the Veterans Affairs Diabetes Trial (VADT) study shows that intensive treatment has no significant effect. A well thought-out analysis of the studies published in 2008 (ACCORD, STENO 2 post-trial, ADVANCE, VADT, UKPDS post-trial, Epidemiology of Diabetes Interventions and Complications [EDIC]) is particularly instructive and highlights the existence of glycaemic memory, the non-existence of blood pressure memory, the need to control all cardiovascular risk factors and to treat diabetes early while avoiding hypoglycaemic incidents. The glycaemic target based on HbA1c must take into account the patient's age and the duration of his diabetes, as well as his cardiovascular risk factors and previous glycaemic control. All in all, the intensive treatment of type 2 diabetes must begin early; it must not be too rapid and must avoid hypoglycaemic incidents and be combined with a strict control of other cardiovascular risk factors.
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PMID:Glycaemic control and cardiovascular morbi-mortality: the contribution of the 2008 studies. 1919 63

The angiotensin-converting enzyme (ACE) inhibitor perindopril (Coversyl) is a long-acting lipophilic drug with a high-tissue affinity for the ACE. ACE inhibition by perindopril has two main effects: it inhibits the angiotensin II formation and potentiates bradykinin. Perindopril is one of the ACE inhibitors that has been extensively studied in randomized clinical trials within various patient populations. The clinical efficacy has been demonstrated in patients with hypertension, diabetes mellitus, cerebrovascular disease, stable coronary artery disease (CAD) and heart failure. Perindopril has a positive safety and tolerability profile. Therefore, perindopril, as an ACE inhibitor, has an established place in the major clinical treatment guidelines. This article discusses several studies that have shown that an antihypertensive treatment with perindopril reduces and prevents cardiovascular events in a large range of patients with established vascular disease. The observed cardioprotective benefits of perindopril were independent of blood pressure. The outcome of these and other trials support the concept of specific cardioprotective properties of ACE inhibition by perindopril in addition to the blood pressure-lowering effects, such as anti-atherosclerotic, anti-inflammatory and antithrombotic properties. In addition, the observed consistency of the treatment benefit across subgroups indicates that the absolute benefits conferred by treatment are mainly established by each patient's future risk of vascular complications, rather than their initial blood pressure level or other risk factors. This article describes these issues according to the main studies with perindopril or perindopril-based regimens, concluding that the blood pressure-dependent and -independent cardioprotective effects extend to all patients with vascular disease. This concept supports the provision of ACE inhibitor-based treatment, not on the basis of arbitrary cut-off points for blood pressure but rather on assessment of vascular risk, which is raised in patients with stable CAD, diabetes and stroke.
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PMID:Angiotensin-converting enzyme inhibition by perindopril in the treatment of cardiovascular disease. 1937 59

Blood flow reduction induces inward remodeling of resistance arteries (RAs). This remodeling occurs in ischemic diseases, diabetes and hypertension. Nonetheless, the effect of flow reduction per se, independent of the effect of pressure or metabolic influences, is not well understood in RA. As angiotensin II is involved in the response to flow in RA, we hypothesized that angiotensin II may also be involved in the remodeling induced by a chronic flow reduction. We analyzed the effect of angiotensin I-converting enzyme inhibition (perindopril) and angiotensin II type 1 receptor blockade (candesartan) on inward remodeling induced by blood flow reduction in vivo in rat mesenteric RAs (low flow (LF) arteries). After 1 week, diameter reduction in LF arteries was associated with reduced endothelium-dependent relaxation and lower levels of eNOS expression. Superoxide production and extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation were higher in LF than in normal flow arteries. Nevertheless, the absence of eNOS or superoxide level reduction (tempol or apocynin) did not prevent LF remodeling. Perindopril and candesartan prevented inward remodeling in LF arteries. Contractility to angiotensin II was reduced in LF vessels by perindopril, candesartan and the ERK1/2 blocker PD98059. ERK1/2 activation (ratio phospho-ERK/ERK) was higher in LF arteries, and this activation was prevented by perindopril and candesartan. ERK1/2 inhibition in vivo (U0126) prevented LF-induced diameter reduction. Thus, inward remodeling because of blood flow reduction in mesenteric RA depends on unopposed angiotensin II-induced contraction and ERK1/2 activation, independent of superoxide production. These findings might be of importance in the treatment of vascular disorders.
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PMID:Involvement of angiotensin II in the remodeling induced by a chronic decrease in blood flow in rat mesenteric resistance arteries. 2053 14

Scavenger receptor A (SR-A) is the main receptor through which oxidized LDL (oxLDL) and advanced glycation end products get into the cells. The aim of the present study was to investigate the effect of an ACE inhibitor, perindopril, on the expression of SR-A in renal tubulointerstitium of diabetic rats. Diabetes was induced in male Sprague-Dawley rats by injection with streptozotocin. The rats were then randomly divided into 3 groups: normal control group; untreated diabetes mellitus group; and diabetes mellitus group treated with the ACE inhibitor, perindopril. After a 24-week treatment, tubulointerstitial injury index was assessed on Masson's trichrome sections. The number of macrophages and the expression of SR-A protein in renal tubulointerstitium were detected by immunohistochemistry and the expression of SR-A mRNA was detected by RT-PCR. The tubulointerstitial injury index, the number of macrophages and the expression of SR-A mRNA were significantly higher in the diabetes group than the normal control group. Perindopril treatment not only attenuated the tubulointerstitial injury and the macrophages infiltration but also reduced the overexpression of SR-A mRNA in diabetic rats. The expression of SR-A protein was most obvious in renal tubulointerstitium in diabetic rats, which was attenuated by perindopril treatment. The findings of the present study indicate that perindopril may have renoprotective effects of diabetic nephropathy via inhibiting the expression of SR-A in renal tubulointerstitium.
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PMID:Perindopril attenuates renal tubulointerstitium injury by inhibiting scavenger receptor A over-expression in diabetic rats. 2176 40

The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized placebo-controlled trial which clearly demonstrated that perindopril-based blood pressure (BP)-lowering treatment is one of the most effective and generalizable strategies for secondary prevention of stroke. Beneficial effects of BP lowering were observed on recurrent stroke, other cardiovascular events, disability, dependency, and cognitive function across a variety of subgroups defined by age, sex, geographical region, body mass index, diabetes, atrial fibrillation, chronic kidney disease, and baseline BP levels. Once patients with stroke have stabilized, all patients should receive BP-lowering therapy irrespective of their BP levels. On the basis of recommendations from current international guidelines, BP should be lowered to <140/90 mm Hg in all patients with cerebrovascular disease and to <130/80 mm Hg if therapy is well tolerated.
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PMID:PROGRESS: Prevention of Recurrent Stroke. 2189 53

Available information regarding the relation among atherosclerosis, low-density lipoproteins, markers of thrombosis, inflammation and endothelial dysfunction has accumulated, but is still very limited, making only minimal contributions to clinical decision-making. Many more clinical trials are needed, but unless there is a relationship between atherosclerosis prevention, specific markers and a pharmaceutical product, financial support for such trials will be difficult to obtain. The anti-inflammatory effect of statins is well established. Angiotensin-converting enzyme inhibitors are generally not thought of as having anti-inflammatory effects, but the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) study observed extensive RR reduction with perindopril. It was explained not simply by control of hypertension, but by reduced activity of multiple factors, supported by specific substudies. The 'cardiovascular continuum' is an excellent unifying term to explain atherosclerosis mechanisms, relate mechanisms to clinical understanding, and assist the clinician in selecting the appropriate prevention and control therapies. This so-called continuum actually describes a relationship among different biochemical, enzymatic and hormonal factors that affect the cardiovascular system. It can be seen in the downregulation of the angiotensin II receptor type 1 by statins, which contributes to hypertension control while lowering low-density lipoproteins. Peroxisome proliferator activator receptor-gamma also demonstrates the cardiovascular continuum with activation of the receptor by glitazones. The glitazones increase insulin sensitivity for diabetes control. Activation of the peroxisome proliferator activator receptor-gamma inhibits inflammation, which is possibly related to atherosclerosis, normalization of endothelial function, suppression of metalloproteinases and a decrease in smooth muscle cell migration. All of these effects may decrease atherosclerosis production while improving control of diabetes mellitus, a key disease in the cardiovascular continuum for development of atherosclerosis. Consideration of such interrelationships is just scratching the surface. Nevertheless, it can be seen that the complicated process of atherosclerosis development has a multifaceted explanation that has been minimally defined, but holds the key to prevention and control of this major medical problem faced in modern society.
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PMID:Coronary atherosclerosis, low-density lipoproteins and markers of thrombosis, inflammation and endothelial dysfunction. 2247 42

High blood pressure, obesity, abnormal lipid profile, which often coexist with diabetes, tend to be associated with preclinical cardiovascular abnormalities and may contribute to the association of diabetes with cardiovascular events. Many studies have proved that streptozotocin (STZ) is responsible for type-2-diabetes-induced cardiovascular complications. Long-term perindopril therapy in patients with hypertension and diabetes has been observed to correct carotid remodeling by reducing hypertrophy. We studied the effect of perindopril (1 mg/kg/d orally [po]) on cardiovascular complications in neonatal model of rats, which was induced by administering STZ (90 mg/kg, intraperitoneally [ip]), in 5-d-old wistar rats and cardiac hypertrophy induced by isoprenaline (ISO; 5 mg/kg, ip) for 10 d. Various biochemical, cardiac, and hemodynamic parameters were measured at the end of 8 weeks of treatment in diabetes model and 10 d in hypertrophy model. STZ produced hyperglycemia, hyperinsulinemia, dyslipidemia, hypertension, bradycardia, increased creatinine kinase (CK-MB), lactate dehydrogenase enzymes (LDH) and C-reactive protein (CRP) levels, cardiac hypertrophy, and oxidative stress. Chronic treatment with perindopril significantly prevented STZ-induced hyperglycemia and hyperinsulinemia and controlled dyslipdemia in diabetic rats. Further, perindopril produced a significant reduction in elevated levels of CRP, LDH, and CK. STZ-induced hypertension and bradycardia were also prevented by perindopril treatment. Perindopril also produced beneficial effect by preventing cardiac hypertrophy as evident from cardiac hypertrophy index and left ventricular hypertrophic index. Perindopril also prevented STZ-induced oxidative stress. Similar results were obtained in ISO-induced cardiac hypertrophic model, which confirms the beneficial role of perindopril in cardiac hypertrophy. In conclusion, our data from both studies suggest that perindopril produced beneficial effect on cardiac complications.
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PMID:Perindopril protects against streptozotocin-induced hyperglycemic myocardial damage/alterations. 2265 91

Perindopril is one of the most prescribed inhibitors of angiotensin converting enzyme, has a large evidence base, which allows to use it in patients with hypertension, diabetes mellitus type 2, coronary heart disease and chronic heart failure. In this review, the author focused on the evidence of organoprotecting properties of perindopril that lie outside lowering blood pressure.
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PMID:[Therapy with perindopril: organoprotection, not just the antihypertensive effect]. 2323 46


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