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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relative importance of various blood pressure indices on cardiovascular risk in people with type 2 diabetes mellitus has not been established. This study compares the strengths of the associations between different baseline blood pressure variables (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], and mean arterial pressure) and the 4.3-year risk of major cardiovascular events in the Action in Diabetes and Vascular Disease: Preterax and Diamicron-Modified Release Controlled Evaluation Study. Mean (SD) age for the 11 140 participants was 65.8 years (6.4 years). During follow-up, 1000 major cardiovascular events, 559 major coronary events, and 468 cardiovascular deaths were recorded. After adjustment for age, sex, and treatment allocation, the hazard ratios (95% CIs) associated with 1 increment in SD for the risk of major cardiovascular events were 1.17 (1.10 to 1.24) for SBP; 1.20 (1.13 to 1.28) for PP; 1.12 (1.05 to 1.19) for mean arterial pressure; and 1.04 (0.98 to 1.11) for DBP. The areas under the receiver operating characteristic curve were slightly higher for SBP and PP compared with mean arterial pressure and DBP for major cardiovascular and coronary events. Using achieved instead of baseline blood pressure values marginally improved the effect estimates for SBP, DBP, and mean arterial pressure, with no significant differences in the areas under the receiver operating characteristic curve between models with SBP and those with PP. In conclusion, SBP and PP are the 2 best and DBP is the least effective determinant of the risk of major cardiovascular outcomes in the relatively old patients with type 2 diabetes mellitus participating in the Action in Diabetes and Vascular Disease: Preterax and Diamicron-Modified Release Controlled Evaluation Study. However, SBP may be the simplest and most useful predictor across a wider range of age groups and populations.
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PMID:Blood pressure variables and cardiovascular risk: new findings from ADVANCE. 1947 Aug 69

Patients with type 2 diabetes mellitus are at increased risk for complications related to both microvascular and macrovascular events. Although glycemic control has been shown to lower the risk of microvascular events, the effect of intensive glycemic control on macrovascular outcomes is less clear. Recently, 3 large randomized controlled trials (Action to Control Cardiovascular Risk in Diabetes [ACCORD], Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation [ADVANCE], and the Veterans Affairs Diabetes Trial [VADT]) have been published to assess the effect of intensive glucose-lowering efforts on macrovascular outcomes, including myocardial infarction, stroke, and death. This article highlights the similarities and differences between the 3 trials with an emphasis on their impact on patient care.
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PMID:Implications of new diabetes treatment trials: should current clinical practice be altered? 1949 42

The selection of appropriate pharmacologic therapy for any disease requires a careful assessment of benefit and risk. In the case of type 2 diabetes, this decision typically balances the benefits accrued from improved glycemic control with the risks inherent in glucose-lowering medications. This review is intended to assist therapeutic decision-making by carefully assessing the potential benefit from improved metabolic control relative to the potential risks of a wide array of currently prescribed glucose-lowering agents. Wherever possible, risks and benefits have been expressed in terms of absolute rates (events per 1000 patient-years) to facilitate cross-study comparisons. The review incorporates data from new studies (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, Action to Control Cardiovascular Risk in Diabetes, and the Veterans Affairs Diabetes Trial), as well as safety issues associated with newer glucose-lowering medications.
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PMID:Type 2 diabetes: assessing the relative risks and benefits of glucose-lowering medications. 2036 59

Cardiovascular complications constitute the major cause of morbidity and mortality in patients with diabetes. The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) provided consistent evidence that intensive glycemic control prevents the development and progression of microvascular complications in patients with type 1 or type 2 diabetes. However, whether intensive glucose lowering also prevents macrovascular disease and major cardiovascular events remains unclear. Extended follow-up of participants in these studies demonstrated that intensive glycemic control reduced the long-term incidence of myocardial infarction and death from cardiovascular disease. By contrast, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, and Veterans Affairs Diabetes Trial (VADT) results suggested that intensive glycemic control to near normoglycemia had either no, or potentially even a detrimental, effect on cardiovascular outcomes. This article discusses the effects of intensive glycemic control on cardiovascular disease, and examines key differences in the design of these trials that might have contributed to their disparate findings. Recommendations from the current joint ADA, AHA, and ACCF position statement on intensive glycemic control and prevention of cardiovascular disease are highlighted.
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PMID:Intensive glycemic control and cardiovascular disease: an update. 2040 53

Routine blood pressure lowering with the fixed combination of perindopril and indapamide in 11,140 patients with type 2 diabetes was very well tolerated and produced substantial benefits in reducing all-cause and cardiovascular mortality, the primary combined outcome of macro- or microvascular events, total coronary events, and total renal events, as reported previously. We present here a wealth of evidence, most of it previously published either in journal articles or in recent abstract form, that the relative risk reductions conferred by the combination of perindopril and indapamide are broadly consistent across subgroups defined by a wide range of baseline characteristics, including blood pressure at entry, age from below 65 to above 75 years, total cardiovascular risk defined according to the European guidelines, stage of chronic disease, and cognitive function. Furthermore, we report that the absolute risk reductions are significantly greater in those with increased cardiovascular risk, with more advanced nephropathy and in older subjects. We confirm that the effects of blood pressure lowering with perindopril-indapamide and of intensive glucose control with the gliclazide modified release (MR)-based regimen are independent and produce substantial additional benefits when combined. We also discuss these results in the context of other major trials and demonstrate how they extend the evidence on the benefits of blood pressure lowering in patients with diabetes. Finally, we present evidence that the results of The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE trial) are broadly generalizable to patients with type 2 diabetes in community practice, and that if the joint benefits from routine blood pressure lowering with perindopril-indapamide and more intensive control with the gliclazide-MR-based regimen were applied worldwide, close to 2 million lives would be saved over the next 5 years.
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PMID:Importance of blood pressure lowering in type 2 diabetes: focus on ADVANCE. 2042 38

A conference was convened by the Korean Diabetes Association and the Korean Endocrine Society on September 7, 2009 to discuss and organize the results of research on intensive glucose control for the prevention of cardiovascular disease in patients with type 2 diabetes. Professor Kyung Soo Park led the conference, and Professors Kwang Won Kim and Ho Young Son acted as chairmen. Professors Doo Man Kim, Tae Sun Park, and Bong Soo Cha reported on intensive glucose control and diabetic complications, including the UK Prospective Diabetes Study (UKPDS), Diabetes Control and Complication Trial (DCCT) research results, the recently published Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), and Veterans Affairs Diabetes Trial (VADT) research, as well as meta-analyses. Professor Jeong-Taek Woo reported on the manuscript written by the committee for the Korean Diabetes Association which dealt with the treatment of diabetes mellitus. Professors Kyung Soo Ko, Joong Yeol Park, Hyun Shik Son, Moon-Kyu Lee, Dong-Won Byun, and Yoon-Sok Chung participated in the discussion and collected information for the manuscript from all of the participants. The aim of the debate was to determine how to establish target goals for intensive glucose control and how to individualize those goals. The participants concluded that there was no need to modify the recommendation of maintaining an HbA1c under 6.5%, the current blood glucose treatment goal that is recommended by the Korean Diabetes Association. In addition, individual target goals for glucose control were recommended depending on the situation of each patient. We report on the consensus statement from the meeting.
Korean Diabetes J 2010 Feb
PMID:Regulation of glucose control in people with type 2 diabetes: a review and consensus. 2053 15

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

The relationship between glycaemia and cardiovascular disease remains controversial. For patients with type 1 diabetes in the Diabetes Control and Complications Trial, intensive glycaemic control reduced microvascular outcomes and, on longer term follow-up, a significant reduction in macrovascular events was observed. For patients with recently diagnosed type 2 diabetes, the findings in the United Kingdom Prospective Diabetes Study were similar; intensive glycaemic control reduced microvascular events during the intervention phase of the study, and a reduction in macrovascular events was observed on longer follow-up. More recently, the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation study showed a microvascular benefit of more intensive blood glucose control in patients with longstanding diabetes, whereas the Action to Control Cardiovascular Risk in Diabetes study showed harm if this was performed rapidly, with increase in weight, hypoglycaemia and mortality. Collectively, these studies suggest that slow and steady intensive control of glycaemia improves outcomes in people with diabetes, and that to reduce mortality this should be commenced early in the management of patients with type 2 diabetes.
Diabetes Obes Metab 2010 Aug
PMID:The effect of intensive glycaemic control on cardiovascular outcomes. 2059 Jul 40

Numerous observational studies have clearly shown a relationship between hyperglycaemia and cardiovascular (CV) disease. However, the United Kingdom Prospective Diabetes Study (UKPDS), which involved subjects with newly diagnosed type 2 diabetes, just failed to show that intensive glucose control significantly reduces CV events. The results of three subsequent large randomised controlled trials, the Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) and the Veterans Administration Diabetes Trial (VADT), that involved approximately 25,000 subjects with established type 2 diabetes also failed to show that intensive glucose control, aiming for a glycated haemoglobin (HbA(1c)) level<7%, significantly reduces CV events. The ACCORD trial even suggested that under certain circumstances, intensive glucose control is associated with an increased risk for CV and all-cause mortality. Although the exact mechanisms responsible for an increase in mortality in the ACCORD trial remain unknown, there was an association between increased rates of mortality with higher rates of severe hypoglycaemia in the intensive glucose control group. In contrast, a 10-year post-randomisation follow-up study of the tight glucose intervention arm of the UKPDS showed that intensive glucose control was associated with a significant reduction in the risk for myocardial infarction (MI), diabetes-related deaths and all-cause mortality. This suggests that early strict glucose control generates a legacy effect that is eventually translated into protection from CV events. Recent meta-analyses of the above randomised trails have also shown that intensive glucose control is associated with a reduced risk of MI, without a clear benefit on other CV diseases such as stroke. Furthermore, these analyses have also shown that intensive glucose control is associated with increased rates of severe hypoglycaemia but not increased rates of CV or all-cause mortality. Aiming for HbA(1c) levels of <7.0% still remains the general target for good glucose control. Under certain circumstances, aiming for lower HbA(1c) levels may be appropriate. This applies in the setting of newly diagnosed diabetes in relatively young individuals without significant co-morbidities and in patients treated with agents that minimise the risk of severe hypoglycaemia such as metformin. Whether this also applies to newer glucose-lowering agents that target the incretin system will depend on CV outcomes of long-term studies which are in progress.
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PMID:Intensive glucose control and cardiovascular outcomes in type 2 diabetes. 2080 81

The aim of this article is to discuss the implications of the results obtained in the latest large-scale clinical trials designed to evaluate the effect of intensive glycemic control on the vascular complications associated with type 2 diabetes mellitus. The current scientific evidence is reviewed and the implications of the ACCORD (The Action to Control Cardiovascular Risk in Diabetes study group), ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Control Evaluation) and VADT (Veterans Affairs Diabetes Trial) clinical trials are discussed. General concerns of the studies and their implications for clinical practice and the management of type 2 diabetes, as well as the questions which still need to be answered by future clinical research are discussed.
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PMID:[Current controversies in glycemic control targets. What do the results of the latest clinical trials tell us about the approach to type 2 diabetes mellitus?]. 2142 May 30


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