Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac artery disease and heart failure are major causes for morbidity and mortality in diabetes in general and in those with chronic kidney disease (CKD) in particular. Hypertension and dyslipidemia are more common in diabetes and the prevalence of coronary artery disease in diabetics is two-fold to four-fold higher than in nondiabetics. In those with CKD the incidence of cardiovascular complications is nearly two-fold higher than those without CKD. Recent studies suggest that the pathophysiology of cardiac disease is complex process involving both microvascular and macrovascular disease. In addition, myocardial lipotoxicity may be a novel contributing factor particularly in type 2 diabetics. Compelling evidence from cardiovascular outcomes trials indicates that treatment with drugs that block the renin-angiotensin system are cardioprotective in diabetics with microalbuminuria and early stages of kidney disease. Multiple risk factor intervention aimed at optimal blood pressure control (BP <130/<80 mmHG), lowering LDL cholesterol below 100 mg/dl, lowering triglyceride level to 150 mg/dl, A1C <6.5%, treatment with an ACE inhibitor or an angiotensin II receptor blocker, administration of once daily low-dose aspirin and smoking cessation together reduce cardiovascular morbidity and mortality in type 2 diabetics. Novel studies including diabetics with nephropathy aimed at improving outcomes in diabetics by treatment of anemia and optimal control of dyslipidemia are now underway. These and other clinical trials should provide important new insights into improving the quality of life in diabetics and ultimately preventing cardiac disease.
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PMID:Heart disease in diabetic patients. 1629 58

Decreased left ventricular long-axis function may be the earliest stage in subclinical heart failure in Type II diabetes. To assess whether a decrease in SBP (systolic blood pressure) or a change in metabolic control would improve the long-axis function, 48 Type II diabetic patients participating in the CALM II (Candesartan and Lisinopril Microalbuminuria II) study were included in the present study. Patients were examined with tissue Doppler echocardiography at baseline and after 3 and 12 months of follow-up. Corresponding blood pressure, fructosamine and HbA(1c) (glycated haemoglobin) values were obtained. During the follow-up period, a decrease in SBP of 8 mmHg was seen (from 141+/-11 mmHg at baseline to 133+/-12 mmHg; P<0.001) and the peak systolic strain rate was significantly improved (from -1.10+/-0.25 at baseline to -1.25+/-0.22; P<0.01). There was a highly significant relationship between the changes in systolic strain rate, HbA(1c) (P<0.001) and fructosamine (P<0.05), and similarly to changes in left ventricular mass (P<0.05), whereas the correlation to the SBP reduction was not significant. Patients with improved glycaemic control, defined as a reduced HbA(1c) value after 12 months of follow-up, had a significantly improved strain rate (from -1.07+/-0.3 s(-1) at baseline to -1.32+/-0.25 s(-1); P<0.01) compared with patients with increases in HbA(1c) (from -1.14+/-0.25 s(-1) at baseline to -1.16+/-0.27 s(-1); P=not significant). The two groups had comparable baseline values of SBP, left ventricular mass, age and disease duration. In conclusion, changes in left ventricular systolic long-axis function are significantly correlated with changes in left ventricular mass, as well as metabolic control, in hypertensive patients with Type II diabetes mellitus.
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PMID:Effects of blood pressure lowering and metabolic control on systolic left ventricular function in Type II diabetes mellitus. 1651 87

Hypertension is a major risk factor for stroke and coronary events in elderly people and clinical trials have shown that treatment of hypertension with various drugs can result in a substantial reduction in cerebrovascular and cardiovascular events. The angiotensin II type 1 (AT1) receptor antagonists are the newest class of antihypertensive agents to be used widely in clinical practice. AT1 receptor antagonists can generally be given once-daily. They are also extremely well tolerated with minimal first-dose hypotension and an incidence of adverse effects similar to that seen with placebo. Adverse event rates are significantly lower than with other classes of antihypertensive drugs including ACE inhibitors. These factors result in improved compliance and increased rates of continuance on therapy. AT1 receptor antagonists show similar efficacy in lowering blood pressure to other classes of antihypertensive agents and their antihypertensive effect is potentiated when they are given concomitantly with low-dose thiazide diuretics. AT1 receptor antagonists are eliminated predominantly by the hepatic route but most are not subject to extensive metabolism and interactions with other drugs are uncommon. This is an advantage in the elderly, who are often receiving multiple medications which increases the risk for adverse drug interactions. Dose adjustments are not usually required in the elderly unless there is plasma volume depletion. Although plasma AT1 receptor antagonist concentrations are generally higher in the elderly than in younger subjects, this pharmacokinetic difference may be balanced by decreased activation of the circulating renin-angiotensin-aldosterone system in the elderly. Recent clinical studies in high-risk hypertensive patients with left ventricular hypertrophy or in patients with diabetic nephropathy or heart failure have demonstrated that AT1 receptor antagonists can improve clinical outcomes to a similar or sometimes greater extent than other antihypertensive agents. Many of these studies have included large numbers of older patients and have confirmed the excellent tolerability profile of these drugs. Thus, AT1 receptor antagonists should be considered as a possible first-line treatment or as a component of combination therapy in patients with type 2 diabetes mellitus and microalbuminuria or nephropathy and as an alternative or additional treatment to ACE inhibitors in patients with heart failure or left ventricular dysfunction. AT1 receptor antagonists also appear to reduce the onset of new diabetes compared with some other antihypertensive drugs. The benefits in terms of organ protection have mainly been seen in studies using higher doses of particular AT1 receptor antagonists and it is not certain at present whether these results can be extrapolated to other members of the class. As the elderly are more likely to have developed organ damage related to hypertension or to have heart failure or diabetes as concomitant conditions, AT1 receptor antagonists represent an appropriate option for many elderly patients. The main disadvantage of these drugs is the cost of the medication but this may be offset by their improved tolerability with fewer adverse reactions and thus increased compliance, resulting in better blood pressure control and fewer clinical events. Overall, AT1 receptor antagonists are well tolerated and efficacious for blood pressure-lowering when given as a single daily dose in elderly patients and have many potential benefits in high-risk hypertensive subjects.
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PMID:The role of angiotensin II type 1 receptor antagonists in elderly patients with hypertension. 1653 36

Valsartan is an angiotensin receptor antagonist that specifically blocks the angiotensin II type 1 receptors. It is an effective and well-tolerated once-daily antihypertensive agent, with a tolerability profile similar to placebo. A recent series of large-scale clinical trials have shown the benefits of valsartan in disease states beyond hypertension. Based on the results of the Val-HeFT (Valsartan in Heart Failure Trial) and VALIANT (Valsartan in Acute Myocardial Infarction Trial) studies, valsartan is indicated for use in patients with heart failure and in patients post-myocardial infarction. Recently, in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial, valsartan was no more cardioprotective than calcium channel blockers, but was shown to reduce the risk of developing new-onset diabetes in hypertensive patients at high risk of cardiac events compared with calcium antagonist treatment. In diabetic patients with microalbuminuria, valsartan has been shown to have benefits beyond those attributable to blood pressure lowering alone.
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PMID:The angiotensin receptor antagonist valsartan: a review of the literature with a focus on clinical trials. 1655 73

Endothelial dysfunction, characterized by impaired nitric oxide activity, constitutes an early step in the pathogenesis of atherosclerotic disease. Prospective studies have shown that impaired endothelium-dependent vasorelaxation and the vasodilatory response of coronary arteries to acetylcholine predict cardiovascular events. Microalbuminuria and estimated glomerular filtration rate, which are both deeply influenced by renal nitric oxide activity, are predictors of cardiovascular outcome and total mortality but develop at a later stage of renal impairment. Endothelial dysfunction reflects early stage renal involvement in the atherosclerotic processes. The Telmisartan versus Ramipril in renal ENdothelium DYsfunction (TRENDY) trial examined endothelial function of the renal vasculature as a therapeutic target in patients with hypertension and type 2 diabetes, but without albuminuria. The rationale was that blockade of the renin-angiotensin system (RAS) is cardio- and renoprotective at later stages of the disease, but the impact of blockade of the RAS at earlier stages of disease is unknown. The results of TRENDY indicate that the endothelial function, as assessed by basal nitric oxide activity, can be improved after RAS blockade. These data complement the results of the Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) trial, which demonstrated that telmisartan and enalapril similarly decelerate the progression of overt diabetic nephropathy. The results of TRENDY are in accordance with the observed changes in peripheral circulation. Endothelium-dependent vasorelaxation could be improved with angiotensin II receptor blockers, but not with diuretics or beta-blockers, in hypertensive patients. Intervention at the beginning of the renal and cardiovascular continuum offers the opportunity to prevent the fatal development towards renal and cardiac failure.
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PMID:Endothelial dysfunction: how can one intervene at the beginning of the cardiovascular continuum? 1660 59

The renin-angiotensin-aldosterone system plays a key role in the regulation of fluid and electrolyte balance. Angiotensin II receptor blockers (ARBs) inhibit angiotensin II type 1 receptors and large clinical trials have shown that they are effective in many cardiovascular diseases including hypertension, heart failure, myocardial infarction and diabetic nephropathy. They lower blood pressure effectively, are very well tolerated and can be used as monotherapy or in combination with other drug classes for the treatment of hypertension. ARBs are particularly suitable for hypertensive patients with co-morbidities such as diabetes, microalbuminuria, proteinuria, left ventricular hypertrophy and heart failure. Unlike angiotensin-converting enzyme inhibitors, ARBs do not cause persistent dry cough. For patients in whom angiotensin-converting enzyme inhibitors are indicated but not tolerated, an ARB should be considered. Periodic monitoring of renal function and electrolytes is required in patients treated with an ARB.
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PMID:Therapeutic potential of angiotensin receptor blockers in hypertension. 1673 15

Diabetes mellitus (DM) is considered a major public health problem in both developed and developing countries due to its chronic complications, at the macro or microcirculation, with great impact on mortality and morbidity in all patients. The disease is considered the end of a pathophysiologic process involving peripheral and hepatic insulin resistance and reduced insulin secretion that have been started years before the clinical diagnosis. Metabolic syndrome (MS) is a disorder that results from the increasing prevalence of obesity worldwide. DM is frequently associated with clinical and laboratory features of MS, like abdominal obesity, hypertension, dyslipidemia and microalbuminuria that are also risk factors for cardiovascular disease. Populational studies have demonstrated increasing prevalence of all the features of MS from pre-diabetes to clinical DM resulting in a great risk of cardiovascular disease. The prevalence of MS in DM type 2 is estimated to be >80%. Glitazones are PPAR-gamma agonists that improve insulin sensitivity. These drugs induce the transcription of genes related to glucose and lipid metabolism, and expression of inflammatory and endothelial proteins associated with atherosclerosis process resulting in an improvement in endothelial function. However several questions need to be clarified regarding the glitazones, in special those associated with their adverse effects such as weight gain, edema and heart failure.
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PMID:[Glitazones and the metabolic syndrome: mechanism of action, pathophysiology and therapeutic indications]. 1676 93

The revised guideline 'Diabetes mellitus type 2' contains several improvements. The HbA1C target level has been lowered to 7% or less. The universal first step in oral therapy has become metformin. The target level for the treatment of hypertension is now a systolic pressure below 140 mmHg. Statins should be prescribed to almost every patient. Finally, ACE-inhibitors are now suggested for all patients with microalbuminuria and hypertension. Some choices made in the present guideline are not evidence-based, e.g. the advice to prescribe pioglitazone to patients with both a body mass index above 27 kg/m2 and cardiovascular disease, but without heart failure. Still, in general, the updated guideline is an important document which has been greatly improved in comparison to the former one.
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PMID:[The practice guideline 'Diabetes mellitus type 2' (second revision) from the Dutch College of General Practitioners; a response from the perspective of internal medicine]. 1709 45

The prevalence and significance of microalbuminuria in hypertensive patients with impaired fasting glucose (IFG) has received very little attention. A total of 10,320 hypertensive patients who attended primary care centers were enrolled in this study, and the final analysis was done in 7625 patients: 1459 without IFG (plasma glucose <100 mg/dl), 3010 with IFG (plasma glucose > or =100 mg/dl and <126 mg/dl), and 3156 with type 2 diabetes (plasma glucose >126 mg/dl). Microalbuminuria was determined using the Micro Albustix reactive strip from Bayer (high urinary albumin excretion [UAE]: Albumin/creatinine ratio > or =3.4 mg/mmol). The proportion of patients with high UAE was 39.4, 48.3, and 65.6%, respectively, in the three groups (P < 0.01 for the trend). The differences in UAE between the group with IFG and the group with normal fasting glucose persisted after adjustment for age, gender, systolic BP, fasting plasma glucose, and cardiovascular comorbidity (odds ratio 1.74; 95% confidence interval 1.08 to 2.80). Hypertensive patients with IFG and high UAE showed a higher prevalence of ischemic heart disease, cardiac insufficiency, left ventricular hypertrophy, atrial fibrillation, and renal insufficiency than the group with normal UAE. Global prevalence of cardiovascular conditions was 30.4% in the group with high UAE compared with 21.4% in the group with normal UAE (odds ratio 1.60; 95% confidence interval 1.31 to 1.95). It is concluded that almost half of hypertensive patients with IFG have high UAE and a higher prevalence of associated cardiovascular involvement and renal insufficiency.
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PMID:Prevalence of abnormal urinary albumin excretion rate in hypertensive patients with impaired fasting glucose and its association with cardiovascular disease. 1713 Feb 59

Thiazolidinediones (TZDs) or glitazones are agents that are widely used for the treatment of type 2 diabetes mellitus. These drugs have a multitude of therapeutic effects including reduction in insulin resistance and hyperglycaemia, anti-inflammatory effects and amelioration of hypertension, microalbuminuria and hepatic steatosis. The TZD molecular target, peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear transcription factor, is expressed diffusely in humans, including many tissues comprising the cardiovascular and renal systems. This suggests a potential for TZDs to elicit perturbing effects on these systems, which are independent of their effects on glucose and lipid metabolism. One of the most common adverse effects of TZDs is fluid retention, which can result in, or exacerbate, oedema and congestive heart failure (CHF). The frequency of peripheral oedema is approximately 5% when TZDs are used in mono- or combination oral therapy, and about 15% when used with insulin. Patients with type 2 diabetes are at high risk of myriad morbid complications, including CHF. The development of CHF, particularly in the elderly, is a harbinger of premature mortality. TZD-induced oedema is largely peripheral, may have its origins in changes in haemodynamics, with some contribution from molecules, which regulate cell and tissue permeability (e.g. vascular endothelial growth factor and protein kinase Cbeta), and remains the preponderant manifestation of TZD-induced fluid retention even in those with existing heart failure. Preclinical and pilot clinical data attest to the fact that at least part of the fluid retention derives from a direct effect of TZDs on sodium reabsorption via the renal medullary collecting duct, a mechanism that is sensitive to diuretic agents that have this nephron segment as their site of action, in whole or in part (spironolactone, amiloride and hydrochlorothiazide). Our review suggests various potential clinical strategies by which TZD-induced fluid retention might be effectively monitored and addressed.
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PMID:Thiazolidinediones and their fluid-related adverse effects: facts, fiction and putative management strategies. 1772 67


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