Gene/Protein Disease Symptom Drug Enzyme Compound
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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among the general heart failure (HF) population, over half have diastolic HF (DHF). The proportion of DHF increases with age, from 46% in patients younger than 45 years to 59% in patients older than 85 years. The diagnosis of DHF is made by the combination of signs and symptoms of HF with preserved systolic function (left ventricular ejection fraction >50%), and evidence of diastolic dysfunction obtained by echocardiographic Doppler examination, invasive hemodynamic evaluation, or an elevation of serum B-type natriuretic peptide. The most common risk factors for the development of diastolic dysfunction and DHF include long-standing hypertension, older age, female sex, obesity, diabetes, chronic kidney disease, and coronary artery disease. Acute decompensation occurs in the setting of pressure overload, volume overload, or superimposed cardiac ischemia. The cornerstones of in-hospital management include blood pressure and volume control, heart rate control, and correction of precipitating factors. Priorities in the outpatient clinic include optimal blood pressure control, maintenance of euvolemia with minimal or no diuretics, and, potentially, use of disease-modifying drugs including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, aldosterone receptor blockers, beta-blockers, and digoxin. Long-term regression of left ventricular hypertrophy, improvement in diastolic filling parameters, and sustained reductions in B-type natriuretic peptide may be future treatment targets for this condition.
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PMID:Curriculum in cardiology: integrated diagnosis and management of diastolic heart failure. 1758 43

Fasudil, a Rho-kinase inhibitor, may improve insulin signaling. However, its long-term effect on metabolic abnormalities and its preventive effect on diabetic nephropathy are still unknown. We assessed these effects of fasudil in insulin-resistant diabetic rats, comparing them with those of an angiotensin II receptor blocker, olmesartan. Male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka, non-diabetic control, rats at 15 weeks of age were used. OLETF rats were randomized to receive a low or a high dose of fasudil or olmesartan for 25 weeks. To examine the therapeutic effects after the development of diabetes, OLETF rats at 30 weeks of age were given fasudil for 10 weeks. Administration of high-dose fasudil completely suppressed the development of diabetes, obesity, and dyslipidemia and increased serum adiponectin levels in OLETF rats. High-dose olmesartan also decreased hemoglobin A1c and increased serum adiponectin. There was a significant correlation between hemoglobin A1c and serum adiponectin or free fatty acid levels. The treatment with high-dose fasudil ameliorated proteinuria, glomerulosclerosis, renal interstitial fibrosis, and macrophage infiltration in OLETF rats. Olmesartan, even at the low dose, suppressed renal complications. The treatment with fasudil after the development of diabetes improved the metabolic abnormalities in OLETF rats, but could not suppress the progression of nephropathy. We conclude that the long-term treatment with fasudil prevents the development of diabetes, at least in part, by improving adipocyte differentiation in insulin-resistant diabetic rats. Early use of fasudil may prevent diabetic nephropathy.
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PMID:A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats. 1733 27

Liver allograft recipients are at increased risk of death from cerebrovascular and cardiovascular disease. We propose the following strategy of risk-reduction, based on currently available literature. Lifestyle: standard advice should be given (avoidance of smoking, excess alcohol and obesity, adequate exercise, reduction of excess sodium intake). Hypertension: target blood pressure should be 140/90 mmHg or lower, but for those with diabetes or renal disease, 130/80 mmHg or lower. For patients without proteinuria, antihypertensive therapy should be initiated with a calcium channel blocker and for those with proteinuria, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker. If monotherapy fails to achieve adequate response, calcium channel blockers and ACE-inhibitors or angiotensin II receptor blockers should be combined. If hypertension remains uncontrolled, an alpha-blocker may be added. Consideration should be given to changing immunosuppression and avoiding use of calcineurin inhibitors. Diabetes: recipients should be regularly screened for diabetes. For patients with new-onset diabetes after transplant, stepwise therapy should be guided by HbA1c concentrations, as with type II diabetes mellitus. Hyperlipidemia: annual screening of lipid profile should be undertaken, with treatment thresholds and targets based on those advocated for the high risk general population. Dietary intervention is appropriate for all patients. A statin should be considered as the first line treatment to achieve specified targets. In patients receiving a calcineurin inhibitor, Pravastatin should be commenced at a dose of 10 mg/day. In patients receiving other forms of immunosuppression, pravastatin may be commenced at a dose of 20 mg/day. Liver tests should be monitored and patients warned to report myalgia. If monotherapy is inadequate, ezetimibe or a fibrate may be added. Consideration may be given to change in immunosuppression if combination lipid-lowering therapy proves inadequate.
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PMID:Reducing the risks of cardiovascular disease in liver allograft recipients. 1749 26

The mounting epidemic of overweight and obesity has made understanding the relationship between excess weight and associated comorbidities more urgent. Obesity is one of the strongest predictors of the development of hypertension and is an independent risk factor for cardiovascular disease, renal disease, and diabetes mellitus. The concomitant presence of obesity and hypertension, as commonly occurs in the cardiometabolic syndrome, magnifies the risk for cardiovascular and renal disease. The term "obesity-hypertension" thus serves to underscore the link between these two deleterious conditions and to emphasize the imperative for clinical intervention. Adipose tissue is now known to produce hormones and cytokines that promote inflammation, lipid accumulation, and insulin resistance. In addition, adipose tissue contains all the components of the renin-angiotensin system (RAS), which is upregulated in the presence of obesity. Evidence implicates activation of the systemic and adipose tissue RAS, as well as the sympathetic nervous system, as key obesity-related mechanisms of hypertension and other components of the cardiometabolic syndrome. RAS blockade therefore becomes a potential therapeutic strategy in patients with obesity-related hypertension and in persons with the cardiometabolic syndrome. Clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers conducted in predominantly overweight/obese populations have demonstrated significant reductions in cardiovascular and renal disease risk among a range of at-risk patients. RAS blockade also is associated with a reduced risk of new-onset diabetes compared with other classes of antihypertensive therapy. Randomized, controlled trials conducted specifically in patients with obesity and hypertension are needed to determine the optimal therapeutic approach for these patients.
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PMID:The role of renin-angiotensin system blockade in the management of hypertension associated with the cardiometabolic syndrome. 1767 2

Abdominal obesity is a risk factor for cardiovascular disease worldwide, and it is becoming a dramatic issue for national health systems. Overweight and obesity are highly associated with multiple comorbidities, elevated blood pressure values, dyslipidaemia, reduced insulin sensitivity and alterations of large and minor vessels. Activation of the renin-angiotensin system (RAS) in adipose tissue may represent an important link between obesity and hypertension. Angiotensin II has been shown to play a role in adipocyte growth and differentiation. Adipocytes also secrete adiponectin, enhancing insulin sensitivity and preventing atherosclerosis. Blockade of the RAS with either an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker results in a substantial increase in adiponectin levels and improved insulin sensitivity. Obesity-related hypertension needs a comprehensive approach to treatment including both weight loss and pharmacological therapies. Antihypertensive drugs prescription should be based on guidelines recommendations for management of hypertension, taking into account the growing evidences about the relationship between some antihypertensive drugs and the development of new-onset diabetes. This review discusses the role of RAS in the relationship between obesity, essential hypertension and insulin resistance.
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PMID:Obesity, essential hypertension and renin-angiotensin system. 1790 24

Several factors have been incriminated in the genesis of diabetic nephropathy. To elucidate their interplay, we have used a hypertensive, obese, diabetic rat model with nephropathy (SHR/NDmcr-cp) that mimics human type 2 diabetes. This model is characterized by hypertension, obesity with the metabolic syndrome, diabetes with insulin resistance, and intrarenal advanced glycation end product (AGE) accumulation. In order to achieve renoprotection, which was evaluated by histology and albuminuria, various therapeutic approaches were used: caloric restriction, antihypertensive agents (angiotensin II receptor blocker [ARB] and calcium channel blocker), lipid- (bezafibrate) or glucose-lowering (insulin and pioglitazone) agents, and cobalt chloride (a hypoxia-inducible factor activator). Altogether, renoprotection is not necessarily associated with blood pressure or glycemic control. By contrast, it is almost always associated with decreased AGE formation, with the exception of insulin, which induces hyperinsulinemia, eventually leading to an overproduction of transforming growth factor-beta. AGE formation is reduced directly by in vitro active compounds (e.g., ARBs) or indirectly by in vitro inactive compounds (e.g., pioglitazone and cobalt). In the latter cases, AGE reduction may reflect a decreased oxidative stress as it is concomitant with a marked reduction of oxidative stress markers. It remains to be seen whether the renoprotection offered by these various approaches may be additive.
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PMID:Inhibition of advanced glycation end products: an implicit goal in clinical medicine for the treatment of diabetic nephropathy? 1844 8

The incidence of end-stage renal disease (ESRD) has been increasing, and within a 10-year period it is predicted that it will increase by 40 %. The main cause of death in this population of more than 50,000,000 individuals worldwide is cardiovascular disease. Increased urinary albumin is a predictor of renal failure, type 1 and type 2 diabetes; it correlates closely with mean arterial pressure in hypertensive subjects, predicts cardiovascular events and has a strong association with the metabolic syndrome. Treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers can reduce progressive renal damage, the beneficial effect being partially independent of the blood pressure lowering actions. Various therapies have proved effective in reducing microalbuminuria and progressive renal damage, demonstrating that the risk factor associated with a clinical outcome decreases with appropriate treatment. Cardiovascular events are the main cause of death in most patients with chronic renal disease. Diabetes, hypertension, obesity and smoking further increase the likelihood of vascular damage. Screening target populations of people with diabetes or hypertension is well recognized. Studies in several countries that have tested for albuminuria in unselected populations have demonstrated associations between microalbuminuria and deteriorating renal function, with the risk of developing ESRD and cardiovascular outcomes. There is some evidence for the use of urinary albumin as a marker of kidney involvement in unselected populations, but this needs to be strengthened and it may be cost effective compared with no screening. This has the potential to have a major impact in developing countries facing the challenges of chronic kidney disease, diabetes and cardiovascular disease.
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PMID:Evidence for the use of urinary albumin as marker of kidney involvement in unselected populations. 1856 65

The development of angiotensin II receptor blockers (ARB) as a new class of drugs for the management of hypertension has elicited the attention of many clinicians worldwide with the aim of improving blood pressure (BP) control as well as cardiovascular protection. Among ARB telmisartan has been shown to be characterised by an antihypertensive efficacy fully covering the 24-hour period, thereby allowing to antagonise the adverse effects of early morning BP rise on cardiovascular risk. Other specific effects of the drug are represented by its favourable metabolic profile (particularly on insulin sensitivity) and neutral effects on sympathetic cardiovascular function. These properties are coupled with cardioprotective effects, documented by the evidence that the drug: 1) is effective in favouring the regression of cardiac and vascular organ damage, 2) reduces arterial stiffness and improves vascular distensibility and 3) reverses the endothelial dysfunction typical of the hypertensive state particularly when complicated by renal failure, diabetes, obesity or metabolic syndrome. Several of these properties can account for the results of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), documenting the beneficial effects on the drug on cardiovascular morbidity and mortality.
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PMID:Cardioprotective effects of telmisartan in uncomplicated and complicated hypertension. 1858 82

Few studies have analyzed intraclass differences in angiotensin II receptor blockers (ARBs) with respect to antidiabetic or metabolic effects. We designed a prospective randomized study to compare a peroxisome proliferator-activated receptor-gamma (PPARgamma)-activating ARB with a nonactivating ARB to delineate the effects on metabolic factors associated with cardiovascular disease. Subjects initially comprised 153 hypertensive patients (72 men, 81 women; mean age, 67.9 +/- 7.8 years) with diagnosed glucose intolerance on the glucose loading test. Patients were randomly assigned to receive 6-month administration of telmisartan 47.0 mg/d (TEL) or candesartan 8.4 mg/d (CAN), or to have no change in drug regimen (control group, CTL). Fasting plasma glucose level was significantly reduced in TEL (n = 46) compared with CTL (n = 47) (percentage of change from baseline, -1.7% vs +2.2%; P = .045). Percentage of increase in adiponectin was significantly larger in TEL than in CTL (+10.5% vs +2.2%, P = .025), but not significantly larger in CAN (n = 44) than in CTL (+4.9% vs +2.2%; P = .13). Percentage of decrease in body weight from baseline was significantly enhanced in TEL compared with CTL (-2.2% vs -0.8%, P = .023) and CAN (-2.2% vs -0.3%, P = .007). Telmisartan decreased body weight while increasing serum adiponectin levels in hypertensive patients with glucose intolerance. Candesartan did not achieve similar improvements in these patients. Among ARBs, telmisartan may have a larger impact on obesity-related diseases that can lead to cardiovascular disorders.
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PMID:Effects of telmisartan on adiponectin levels and body weight in hypertensive patients with glucose intolerance. 1880 55

Fatty liver is one of the local morphological manifestations of metabolic syndrome and is frequently associated with insulin resistance. Insulin resistance is also common in patients with chronic hepatitis C. Hyperinsulinemia is an independent risk factor for hypertension and cardiovascular mortality. The aim of this study was to evaluate the therapeutic efficacy of angiotensin II receptor blockers (ARBs), telmisartan and olmesartan, for patients with non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CH-C). We analyzed the incidence of obesity, insulin resistance, and other disorders in patients with NAFLD (Group A), CH-C (Group B), or other liver diseases (Group C). We evaluated whether the ARBs, telmisartan and olmesartan, improved insulin resistance and liver injury by measuring the homeostasis model assessment ratio of insulin resistance (HOMA-IR) and serum alanine aminotransferase (ALT). The incidence of obesity (BMI > or =25 kg/m2) was significantly higher in Group A than in Groups B and C. The incidence of insulin resistance (HOMA-IR > or =2.5) in Groups A and B was significantly higher than in Group C. Regular doses of telmisartan and olmesartan significantly improved HOMA-IR and ALT levels not only in NAFLD patients but also in patients with CH-C. The effects tended to be more notable with telmisartan. In conclusion, telmisartan and olmesartan improved insulin sensitivity and may possibly be used as liver protecting agents in CH-C as well as NAFLD patients.
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PMID:Therapeutic effect of ARBs on insulin resistance and liver injury in patients with NAFLD and chronic hepatitis C: a pilot study. 1881 60


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