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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

30-50% of patients presenting with symptoms of congestive heart failure exhibit a near normal left ventricular systolic function at rest, and an impaired diastolic function of the heart may be causative. Despite a better prognosis than in systolic heart failure, frequency of hospitalizations due to diastolic heart failure is comparable with systolic heart failure. According to the criteria of Vasan and Levy diagnosis of diastolic heart failure is probable, if symptoms and signs of heart failure are accompanied in proximity (within 72 h) by objective evidence of normal left ventricular systolic function. Newer echocardiographic techniques (e. g., tissue Doppler) aid to confirm the diagnosis and to determine the severity of dysfunction and may substitute invasive demonstration of impaired left ventricular relaxation, filling, compliance or stiffness for standardized diagnosis. Incorporation of biochemical test (BNP [brain natriuretic peptide]) allows differential diagnosis and may increase the accuracy of diagnosis. Due to inconsistent diagnostic criteria, data from prospective randomized controlled trials for the treatment of diastolic heart failure are rare. Basic principles include treatment of the underlying disease, i. e., control of hypertension, diabetes, or obstructive airway disease. Angiotensin 1 antagonists (ARB) have proven effective in regression of left ventricular hypertrophy (LIFE) and may reduce morbidity, but not mortality (CHARM). Maintenance of sinus rhythm, heart rate control (beta-blockers, calcium channel blockers) and anti-ischemic therapy may be indicated in view of pathophysiological aspects. Diuretics should be administered with caution in patients with symptoms of congestion, digitalis is not useful in the treatment of isolated diastolic heart failure. The results of ongoing trials (e. g., I-Preserve) may offer new therapeutic options, and evidence-based guidelines for the so far often unsatisfactory treatment of diastolic dysfunction/heart failure are awaited.
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PMID:[Dyspnea and normal systolic function]. 1591 35

The adipose-specific protein adiponectin has been recently discovered to improve insulin sensitivity. Angiotensin type-1 receptor (AT1R) blockers (ARBs) reduce the incidence of type 2 diabetes mellitus by mostly unknown molecular mechanisms. To identify new antidiabetic mechanisms of ARBs, we studied the regulation of adiponectin by angiotensin II (Ang II) and different ARBs in murine 3T3-L1 adipocytes and obese Zucker rats. Adiponectin protein expression was markedly stimulated by Ang II (5 nmol/L), which was inhibited by blockade of the AT2R, and further enhanced by the ARB irbesartan. Irbesartan-mediated adiponectin upregulation started beyond the concentrations needed for AT1R blockade and was also present in the absence of Ang II, implicating an AT1R-independent mechanism of action. Recently, certain ARBs (irbesartan, telmisartan) were identified as ligands of the peroxisome proliferator-activated receptor (PPAR)gamma. Telmisartan also stimulated adiponectin protein expression, whereas the non-PPARgamma-activating ARB eprosartan had no effect. Blockade of PPARgamma activation by the PPARgamma antagonist GW9662 markedly inhibited irbesartan-induced adiponectin expression. Cognate mRNA levels of adiponectin were not affected by ARBs. Kinetic studies using the protein synthesis inhibitor cycloheximide showed that irbesartan prevented the cellular depletion of adiponectin protein. Finally, administration of irbesartan to obese Zucker rats improved insulin sensitivity and attenuated adiponectin serum depletion. The present study demonstrates that AT2R activation and certain ARBs induce adiponectin in adipocytes, which was associated with an improvement of parameters of insulin sensitivity in vivo. ARB-induced adiponectin stimulation is likely to be mediated via PPARgamma activation involving a post-transcriptional mechanism.
Hypertension 2005 Jul
PMID:PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin. 1593 9

The metabolic syndrome leads to cardiovascular disease and type 2 diabetes mellitus, through multiple risks, such as insulin resistance, dyslipidemia, hyperinsulinemia, and hypertension. It also represents a disorder of partial genetic background as mutations of the peroxisome proliferator-activated receptor-gamma (PPAR-g). Thiazolidinedione agonists for the PPAR-g system are effective in control of insulin resistance and diabetes. Telmisartan has a molecular structure that imparts partial agonist properties with the PPAR-g molecule, which results in reductions in glucose and lipid metabolism. Administration of telmisartan to rats on a high-fat, high-carbohydrate diet leads to reductions in glucose, insulin, and triglyceride levels. The results imply that the ARB agent, telmisartan, could treat both the hemodynamic and metabolic aberrations seen in subjects with the metabolic syndrome, such as insulin resistance, glucose intolerance, and hypertension.
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PMID:Angiotensin-receptor blocking agents and the peroxisome proliferator-activated receptor-gamma system. 1606 Oct 40

The benefits of reducing blood pressure (BP) on the risks of major cardiovascular event and preservation of renal function are well established in patients with hypertension. We estimated effects of strategies based on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ARB) and calcium channel antagonist (CCB), which is predominantly prevalent in Japan in patients with hypertenstion than ACEI/ARB, on the risks of these events, overviewed with data from clinical trials and meta-analysis of these trials including underwent in Japan. ACEI and ARB-based regimens reduced the risks of heart failure and progression of renal dysfunction complicated with and without diabetes mellitus (DM) in patients with hypertension compared with control and CCB-based regimens. CCB-based regimens reduced the primary risks of cerebella event and dementia and primary and secondary risks of coronary events in patients with hypertension having many coronary risk factors compared with control and ARB/ACEI-based regimens. Greater risk reductions, however, were produced by regimens that targeted lower (BP) goals, by combined regimens based on ACEI/ARB and CCB and diuretics, demonstrated in mega-trial of ALLHAT and proposed in guideline of JSH 2004.
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PMID:[Evidence-based usefulness of Ca antagonists and ACEIs and ARBs for the primary and secondary prevention of major cardiovascular and renal events in patients with hypertension]. 1619 17

Therapy with losartan compared to irbesartan was performed in a Chinese sample of hypertensive patients with elevated serum uric acid (SUA) levels. After 1 week of screening and a 2 week single-blinded placebo baseline period, patients were treated for 4 weeks with losartan 50 mg or irbesartan 150 mg. After 4 weeks, patients with SiDBP <90 mmHg and SiSBP <140 mmHg continued the same dose regimen for another 4 weeks. If blood pressure was not controlled after 4 weeks of treatment, the dose of either regimen was doubled to losartan 100 mg and irbesartan 300 mg. There were 351 patients randomized (176 to losartan and 175 to irbesartan), and of these, 325 patients completed the study (162 in the losartan group and 163 in the irbesartan group). At baseline, the median SUA level in the losartan group was 422 and 420 micromol/l in the irbesartan group. At 8 weeks of therapy, SUA decreased by 63 mumol/l in the losartan group compared to 12 mumol/l in the irbesartan group (P < 0.0001). Blood pressure declined comparably in both groups from 151/92 mmHg at baseline to 137/83 and 135/83 (losartan and irbesartan, respectively, NS). No severe AEs were found for either treatment group. Therapy with losartan decreased SUA levels significantly more than irbesartan in Chinese patients with hypertension and elevated SUA levels, demonstrating the unique uricosuric effect of this ARB in this ethnic group.
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PMID:Effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia in Chinese population. 1628 Oct 62

Chronic kidney disease (CKD) is a major public health problem in the United States. It is estimated that nearly 20 million Americans have some degree of chronic kidney disease defined as an estimated glomerular filtration rate of less than sixty milliliters per minute or evidence of kidney damage by imaging study, biopsy, biochemical testing or urine tests with an estimated glomerular filtration rate more than sixty milliliters per minute. Hypertension is present in more than 80% of patients with CKD and contributes to progression of kidney disease toward end stage (ESRD) as well as to cardiovascular events such as heart attack and stroke. In fact the risk for cardiovascular death in this patient population is greater than the risk for progression to ESRD. Proteinuria is an important co-morbidity in hypertensives with CKD and increase risk of disease progression and cardiovascular events. Treatment of hypertension is therefore imperative. The National Kidney Foundation clinical practice guidelines recommend a blood pressure goal of <130 mmHg systolic and <80 mmHg diastolic for all CKD patients. Recent post-hoc analyses of the Modification of Diet in Renal Disease study indicate that lower blood pressure may provide long-term kidney protection in patients with nondiabetic kidney disease. Specifically a mean arterial pressure <92 mmHg (e.g. 120/80 mmHg) as compared to 102-107 mmHg (e.g. 140/90 mmHg) is associated with reduced risk for ESRD. In most cases achieving this goal requires both non-pharmacologic and pharmacologic intervention. Dietary sodium restriction to no more than 2 grams daily is important. In addition, moderate alcohol intake, regular exercise, weight loss in those with a body mass index greater than 25 kg/M(2) and reduced amount of saturated fat help to reduce blood pressure. The first line pharmacologic intervention should be an angiotensin converting enzyme inhibitor or angiotensin II type 1 receptor blocker in those with diabetes or non-diabetics with more than 200 mg protein/gram creatinine on a random urine sample. For non-diabetics with less than 200 mg protein/gram creatinine on a random urine sample, no specific first-line drug class is recommended. After initial dosing with an ACEi, ARB or other drug, a diuretic should be added to the regimen. Thereafter, beta-blockers, calcium channel blockers, apha blockers and alpha 2 agonists (e.g. clonidine) and finally vasodilators (e.g. minoxidil) should be added to achieve blood pressure goal. Combinations of ACEi and ARB are helpful in reducing proteinuria and may also lower blood pressure further in some some cases. Blood pressure should be monitored closely in hypertensive patients with CKD and both clinic and home blood pressure measurements may help the clinician adjust treatment.
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PMID:Treatment of hypertension in chronic kidney disease. 1629 69

Ang II (Angiotensin II) has been shown to play a pivotal role in the pathophysiology of various organs, especially the cardiovascular system. The effects of ARBs (Ang II receptor blockers) in the treatment of hypertension, congestive heart failure and myocardial fibrosis have been analysed extensively in human trials, as well as animal models, and the focus of interest is now directed to its pleiotropic effects, especially on inflammatory disorders. To investigate the effects of a new ARB, olmesartan, on immune-mediated myocardial injury, the protective effects of olmesartan on the development of murine acute myocarditis caused by CVB3 (coxsackievirus B3) were analysed. Olmesartan and a non-specific vasodilator hydralazine lowered systolic blood pressure of mice on day 7 after virus inoculation to a similar extent. Olmesartan significantly decreased myocardial inflammation compared with controls, whereas hydralazine significantly increased this. Olmesartan significantly decreased the expression of IFN-gamma (interferon-gamma), FasL (Fas ligand), iNOS (inducible nitric oxide synthase) and PFP (pore-forming protein) in myocardial tissue, indicating that olmesartan suppressed the activation of infiltrating killer lymphocytes. Olmesartan also decreased the expression of CVB3 genomes in myocardial tissue as well as serum levels of 8-OHdG (8-hydroxy-2'-deoxyguanosine), a biomarker of oxidative-stress-induced DNA damage. The findings suggest that olmesartan prevents myocardial damage and may improve the prognosis of patients with acute myocarditis; however, further investigations are needed before clinical use.
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PMID:Effect of the angiotensin II receptor blocker olmesartan on the development of murine acute myocarditis caused by coxsackievirus B3. 1633 7

The hypertensive patient with type 2 diabetes is especially at risk of adverse cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS) and Hypertension Optimal Treatment (HOT) studies suggested that treatment to a lower target blood pressure resulted in better prevention of clinical disease in these patients. Most trials comparing antihypertensive drugs have shown only minimal differences between the various agents. The evidence from the trials suggests that diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and the angiotensin-receptor antagonists (ARBs) will all successfully reduce adverse clinical events. The largest of the comparative hypertensive drug trials, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), demonstrated that a diuretic has a better hypotensive effect, and was more successful in preventing many aspects of cardiovascular disease compared with CCBs and ACE inhibitors. The importance of good blood pressure control and the general equivalence of antihypertensive drugs were again shown in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which compared an ARB with a CCB. Choice of antihypertensive agent should be individualized and guided by the presence of concomitant clinical disease and the need to protect any specific target organ system in the diabetic hypertensive. Diuretics, being potent hypotensive drugs with clearly demonstrated clinical benefit, should form part of the antihypertensive regimen of most diabetic hypertensives. ACE inhibitors and ARBs are especially useful in preventing nephropathy. Most patients will require a combination of antihypertensive drugs to achieve tight blood pressure control of under 130/80 mm Hg in the diabetic hypertensive. The clinician should concentrate on seeking this lower target blood pressure rather than be excessively concerned about which is the best antihypertensive agent.
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PMID:Choice of antihypertensive drug in the diabetic patient. 1636 52

We tested the hypothesis that blockade of angiotensin II type 1 receptors reduces oxidative stress markers in parallel with urinary albumin and type IV collagen excretions. Sixty-six diabetic patients with nephropathy were randomly assigned to either the angiotensin II receptor blocker (ARB; n=33) or trichlormethiazide (n=33) group. The majority of patients had been treated with angiotensin-converting enzyme inhibitors or calcium channel blockers for > or =1 year before the present study. Reduction of blood pressure was not different between the 2 groups, and HbA1c levels did not change over the study period (8 weeks). Treatment with ARB (candesartan 8 mg/day, n=11 or valsartan 80 mg/day, n=22) for 8 weeks reduced the levels of plasma monocyte chemoattractant protein 1, interleukin 6, urinary 8-epi-prostaglandin F2alpha, 8-hydroxydeoxyguanosine, albumin, and type IV collagen, whereas the levels of these markers were not altered with trichlormethiazide (2 mg/day). Significant correlation was observed between the reduction of the urinary 8-epi- prostaglandin F2alpha and 8-hydroxydeoxyguanosine and those of the urinary albumin and type IV collagen. Subjects with large oxidative stress had large reduction rates because of ARB administration and showed large urinary albumin suppression. These results suggest that ARBs reduce oxidative stress and inflammation in diabetic patients independent of their effects on blood pressure. In addition, increases in oxidative stress caused by angiotensin II may play an important role in the progression of diabetic nephropathy. Our results may help to explain the clinical observation that ARB reduces urinary albumin excretion very efficiently in some patients but not in others.
Hypertension 2006 Apr
PMID:Angiotensin II type 1 receptor blockers reduce urinary oxidative stress markers in hypertensive diabetic nephropathy. 1650 7

Diabetes Mellitus is thought as the presymptomatic stage to cause various vascular diseases. From the point of view that diabetes is already a disease, this paper discusses the prevention of the manifestation of diabetes in the elderly. STOP-NIDDM study demonstrated that acarbose, an alpha-glucosidase inhibitor, reduced the onset of diabetes in impaired glucose tolerance (IGT) subjects by 24%. On the other hand, the Diabetes Prevention Program (DPP) study for IGT subjects revealed that intensive life style intervention prevented diabetes most powerfully by 58% and metformin treatment also reduced by 31%. Furthermore, HOPE, LIFE, and SCOPE studies against hypertension showed that ACI or ARB reduced diabetes by 20-32%, and the WOSCOT study that pravastatin, a HMG-CoA reductase inhibitor, reduced diabetes by 30%. These accumulated results suggest that the most suitable strategy to prevent diabetes in the elderly is intensive life style intervention, and in cases incapable of exercise and diet therapy, acarbose or metformin are recommended for IGT. When associated with hypertension and/or hyperlipidemia, the subjects have to receive ACI or ARB and statins to prevent diabetes.
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PMID:[Prevention of the manifestation of diabetes in the elderly in the presymptomatic stage]. 1652 11


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