9 research outputs found
Antihypertensive therapy, new-onset diabetes, and cardiovascular disease
Type 2 diabetes mellitus is a worldwide epidemic with considerable health and economic consequences. Diabetes is an important risk factor for cardiovascular disease, which is the leading cause of death in diabetic patients, and decreasing the incidence of diabetes may potentially reduce the burden of cardiovascular disease. This article discusses the clinical trial evidence for modalities associated with a reduction in the risk of new-onset diabetes, with a focus on the role of antihypertensive agents that block the renin–angiotensin system. Lifestyle interventions and the use of antidiabetic, anti-obesity, and lipid-lowering drugs are also reviewed. An unresolved question is whether decreasing the incidence of new-onset diabetes with non-pharmacologic or pharmacologic intervention will also lower the risk of cardiovascular disease. A large ongoing study is investigating whether the treatment with an oral antidiabetic drug or an angiotensin-receptor blocker will reduce the incidence of new-onset diabetes and cardiovascular disease in patients at high risk for developing diabetes
Ambulatory Blood Pressure Values in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET)
Pre-hypertension: how low to go and do drugs have a role?
People with pre-hypertension (high blood pressure but below the conventional threshold for intervention with antihypertensive drugs) undoubtedly have increased risk of cardiovascular and other complications. However, the vast majority has low absolute risk and whether treatment would be beneficial is uncertain. While pharmacotherapy has attractions from a public health perspective, clinicians and crucially those with pre-hypertension require robust evidence that drug treatment will lead to short term as well as long term gains. Any changes in recommendations should await adequately powered outcome studies which provide solid evidence of the magnitude of absolute risk reduction in treating pre-hypertension and assessment of the cost-effectiveness
Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms.
The inhibition of the renin-angiotensin system (RAS) with either angiotensin converting enzyme inhibitors (ACEIs) or AT1 angiotensin receptor blockers (ARBs) consistently and significantly reduces the incidence of type 2 diabetes in patients with hypertension or congestive heart failure. The mechanisms underlying this protective effect appear to be complex and may involve an improvement of both insulin sensitivity and insulin secretion. These two effects may result, at least in part, from the well known effects of these pharmacological agents on the vascular system on the one hand, on the ionic balance on the other hand. Indeed, the vasodilation induced by ACEIs or ARBs could improve the blood circulation in skeletal muscles, thus favouring peripheral insulin action, but also in the pancreas, thus promoting insulin secretion. Preserving cellular potassium and magnesium pools by blocking the aldosterone effects could also improve both cellular insulin action and insulin secretion. However, besides these classical effects, new mechanisms have been recently suggested. A direct effect of the inhibition of angiotensin and/or of the enhancement of bradykinin on various steps of the insulin cascade signalling has been described as well an increase in GLUT4 glucose transporters after RAS inhibition. Furthermore, it has been demonstrated that angiotensin II inhibits adipogenic differentiation of human adipocytes via A1 receptors and, therefore, it has been hypothesised that RAS blockade may prevent diabetes by promoting the recruitment and differentiation of adipocytes. Finally, some lipophilic ARBs appear to induce PPAR-gamma activity in the adipose tissue. Hence, the protection against type 2 diabetes observed after RAS inhibition may be partially linked to a thiazolidinedione-like effect. In conclusion, numerous physiological and biochemical mechanisms could explain the protective effect of RAS inhibition against the development of type 2 diabetes in individuals with arterial hypertension or congestive heart failure. What might be the main mechanism in the overall protection effect of ACEIs or ARBs remains an open question
The cardiac MRI substudy to ongoing telmisartan alone and in combination with ramipril global endpoint trial/telmisartan randomized assessment study in ACE-intolerant subjects with cardiovascular disease: analysis protocol and baseline characteristics
Background: The ONTARGET and TRANSCEND clinical trials were designed to investigate the cardioprotective effects of telmisartan 80 mg and ramipril 10 mg, alone and in combination, in patients at high risk of cardiovascular disease. Cardiac MRI enables investigation of mechanistic effects of these agents on cardiac structural and functional variables. Here, we report the design, analysis protocol, reproducibility and relevant quality control procedures, and baseline patient characteristics of the ONTARGET/TRANSCEND cardiac MRI substudy. MRI was undertaken in 330 subjects enrolled in ONTARGET, and 38 subjects in TRANSCEND, across eight centers in six countries. Analyses were performed by two independent analysts using guide-point modeling. Cases with discrepancies in LV mass (LVM) of >5% were independently reanalyzed. Cases with discrepancies in end-diastolic volume (EDV) of >5%, or end-systolic volume (ESV) of >12%, were then reconciled by consensus. Results: Baseline characteristics were broadly similar to the main ONTARGET/TRANSCEND trials, except for a higher frequency of coronary artery disease and Asian ethnicity in the substudy. Reproducibility of MRI analyses (mean ± SD) were 2.8 ± 3.7 ml in EDV, -0.3 ± 3.6 ml in ESV, 3.1 ± 3.3 ml in SV, 1.1 ± 1.8% in EF, and 0.4 ± 4.5 g in LVM. Subgroup analyses revealed increased ESV and LVM, and reduced EF, in subjects with a history of either coronary artery disease or myocardial infarction. Conclusions: The ONTARGET/TRANSCEND cardiac MRI substudy protocol provides for a reliable assessment of the effects of telmisartan and ramipril, alone and in combination, on cardiac structural and functional parameters over a 2-year follow-up period