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Query: UMLS:C0018801 (heart failure)
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Recent trials have helped to clarify indications for the initial pharmacological therapy of hypertension. Both the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and World Health Organization-international Society of Hypertension (WHO-ISH) recommendations should be revised. The more recent trials indicate that: (1) diuretics and beta-blockers appear to be as effective in reducing overall morbidity/ mortality as other agents (Swedish Trial in Old Patients with Hypertension [STOP-2], United Kingdom Prospective Diabetes Study [UKPDS], Intervention as a Goal in Hypertension Treatment [INSIGHT], Nordic diltiazem [NORDIL]); (2) the use of an a-blocker results in more cardiovascular events, especially congestive heart failure, when compared with a diuretic (Antihypertensive Therapy and Lipid Lowering Heart Attack Trial [ALLHAT]); (3)the use of an angiotensin-converting enzyme (ACE) inhibitor results in fewer myocardial infarctions and episodes of heart failure than calcium channel blockers in the elderly and in diabetic patients (Fosinopril vs. Amlodipine Cardiovascular Events Randomized Trial [FACET], Appropriate Blood Pressure Control in Diabetes [ABCD], STOP-2) - other data (Captopril Prevention Project [CAPPP]) suggest that the use of an ACE inhibitor is preferred in diabetic patients; (4) overall cardiovascular events are similar with calcium channel blockers compared with a diuretic - however, there are fewer strokes with non-dihydropyridine calcium channel blockers (NORDIL) and a trend towards an increase in heart failure and myocardial infarctions with either a dihydropyridine or non-dihydropyridine calcium channel blockers compared with a diuretic (INSIGHT, NORDIL); (5) angiotensin receptor blockers (ARBs) will decrease proteinuria and slow progression of renal disease in type 2 diabetic patients when compared with regimens that do not include an ARB or an ACE inhibitor (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL], Irbesartan Type II Diabetic Nephropathy Trial [IDNT], Irbesartan Type II Diabetes with Microalbuminuria [IRMA Il]). The debate over initial therapy may be moot. High-risk hypertensive patients should probably be treated initially with combination therapy, one of which should be a diuretic. The use of diuretics and beta-blockers as well as ACE-inhibitors alone or with a diuretic should be considered as initial therapy (a change from JNCVI). Alpha-blockers should be reserved for special situations, i.e. prostatic hypertrophy (in contrast to WHO-ISH recommendations). An ACE-inhibitor or ARB, usually along with a diuretic, can be considered as preferred therapy in hypertensive diabetic patients. Some data suggest equal or greater reduction in strokes with a calcium channel blocker than other medications.
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PMID:Current recommendations for the treatment of hypertension: are they still valid? 1199 97

Albuminuria has been shown to identify patients with an increased cardiovascular risk, and in clinical studies ACE inhibitors reduce the urinary protein excretion. It was the primary aim of this intensified monitoring project to determine whether these results can be reproduced in a clinical practice setting. Micro- (2.7-22.6 mg albumin/mmol creatinine) or macroalbuminuria (>22.6 mg/mmol) was confirmed by a central laboratory in 598 out of 773 patients with hypertension who had albuminuria >50 mg/l on a Micral Test II performed by 147 general practitioners. Coronary heart disease (prevalence rates 15% in patients with normalbuminuria, 33% in patients with microalbuminuria, and 40% in patients with macroalbuminuria), heart failure (prevalence rates 19, 29, and 32%, respectively), left ventricular hypertrophy (prevalence rates 30, 42, and 38%, respectively), and peripheral vascular disease (prevalence rates 7, 15, and 20%, respectively) were significantly more common in patients with elevated urinary albumin excretion. 230 patients with microalbuminuria and 202 subjects with macroalbuminuria were treated with the angiotensin-converting enzyme inhibitor ramipril for 6 months. The treatment significantly lowered mean arterial blood pressure (from a median value of 120 mm Hg, quartiles 113-125 mm Hg, to 103 mm Hg, quartiles 100-109 mm Hg) as well as urinary albumin excretion (from a median value of 18 mg/mmol creatinine, quartiles 7.2-54.6 mg/mmol creatinine, to 6.5 mg/mmol creatinine, quartiles 1.6-23.1 mg/mmol creatinine). The treatment efficacy was unaffected by age, body mass index, and smoking status. Patients with diabetes mellitus type II and heart failure also had a significant, although less pronounced reduction of albuminuria. In summary, we conclude that ramipril is able to reduce the urinary albumin excretion in a clinical practice setting, as has been shown in clinical studies. However, the treatment response is not completely uniform, as special patient populations seem to be more resistant to therapy.
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PMID:Results from the TIP (Tritace in Proteinuria) intensified monitoring project. 1207 88

Metabolic Syndrome X is a clinical entity which comprises the following factors: diabetes mellitus, arterial hypertension, high levels of triglyceride and/or low levels of HDL cholesterol, central obesity and microalbuminuria (by WHO criteria). The first goal of this study was to determine the frequency of the Metabolic Syndrome X (MSX) in patients with acute myocardial infarction compared with the general population. The second goal of the study was to examine the frequency of heart failure and reinfarction rate in the patients with myocardial infarction, with and without MSX. Furthermore, the relationship between gender and MSX was analyzed. A total of 101 patients with acute myocardial infarction took part in randomized trial (32 women and 69 men). MSX and all of its components were diagnosed according to WHO criteria. To determine statistical significance of our results, we used chi2 test and t-test for independent samples. From 101 patient 48 had MSX (47.52%), while in the general population incidence of MSX is 3-4%. The reinfarction and the heart failure rate were significantly higher in the group of patients with MSX (p = 0.0067 and p = 0.0217, respectively). To conclude, the results of the present study confirm that MSX is a high risk factor for myocardial infarction and its complications.
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PMID:Metabolic syndrome X--high risk factor for acute myocardial infarction and its complications. 1213 4

Arterial hypertension and diabetes are potent independent risk factors for cardiovascular, cerebral, renal and peripheral (atherosclerotic) vascular disease. The prevalence of hypertension in diabetic individuals is approximately twice that in the non-diabetic population. Diabetic individuals with hypertension have a greater risk of macrovascular and microvascular disease than normotensive diabetic individuals. Hypertension is a major contributor to morbidity and mortality in diabetes, and should be recognized and treated early. Type 2 diabetes and hypertension share certain risk factors such as overweight, visceral obesity, and possibly insulin resistance. Life-style modifications (weight reduction, exercise, limitation of daily alcohol intake, stop smoking) are the foundation of hypertension and diabetes management as the definitive treatment or adjunctive to pharmacological therapy. Additional pharmacological therapy should be initiated when life-style modifications are unsuccessful or hypertension is too severe at the time of diagnosis. All classes of antihypertensive drugs are effective in controlling blood pressure in diabetic patients. For single-agent therapy, ACE-inhibitors, angiotensin receptor blocker, beta-blockers, and diuretics can be recommended. Because of concerns about the lower effectiveness of calcium channel blockers in decreasing coronary events and heart failure and in reducing progression of renal disease in diabetes, it is recommended to use these agents as second-line drugs for patients who cannot tolerate the other preferred classes or who require additional agents to achieve the target blood pressure. The choice depends on the patients specific treatment indications since each of these drugs have potential advantages and disadvantages. In patients with microalbuminuria or clinical nephropathy, both ACE-inhibitors and angiotensin receptor blockers are considered first line therapy for the prevention of and progression of nephropathy. Since treatment is usually life-long, cost effectiveness should be included in treatment evaluation.
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PMID:[Treatment of hypertension in type 2 diabetes mellitus--2002 update]. 1223 35

Despite of dramatic improvement in diagnostic procedures and treatment of diabetic patients, cardio-vascular complications are still the most frequent causes of death in these patients. Diabetes influences myocardial and coronary vessels function by coexisting macroangiopathy, microangiopathy, metabolic disturbances and autonomic nervous system neuropathy. All these factors result in diastolic and systolic dysfunction of the heart. Cardiomyopathy, congestive heart failure and serious arrhythmias are the end stage of diabetic complications. Macroangiopathy demonstrates accelerated atherosclerosis (involving coronary arteries), which consequences can be observed in 1 type diabetes patients at around the age of 30. Causes of increased risk of macroangiopathy in type 1 diabetic patients are not clear. There are not many clinical, prospective trials which can allow for etiology determination of the increased incidence of atherosclerosis and mortality due to coronary artery disease in this population. Adding to traditional risk factors of atherosclerosis like genetic factors, hypertension, dyslipidemia, obesity, smoking and improper diet, other important risk factors are observed in diabetic patients. Only few clinical trials suggest that hyperglycemia, glycation, glycoxidation of proteins, lipoproteins, changes in their composition, microalbuminuria, coagulation, fibrinolytic disturbances are additional risk factors of endothelium dysfunction and atherosclerosis. Prevention and treatment of accelerated coronary artery disease and it's consequences are more complicated in the diabetic population than in others. Some of the clinical trials suggest that even improved glycemic control does not eliminate the elevated risk of coronary artery disease in type 1 diabetic patients.
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PMID:[Myocardial and coronary vessel dysfunction in diabetes I patients]. 1251 40

In people with diabetes, renal disease tends to progress from microalbuminuria to clinical proteinuria to renal insufficiency. Little evidence has been published for the nondiabetic population. This study retrospectively analyzed changes of proteinuria over 4.5 yr in the HOPE (Heart Outcomes and Prevention Evaluation) study, which compared ramipril's effects to placebo in 9297 participants, including 3577 with diabetes and 1956 with microalbuminuria. This report is restricted to 7674 participants with albuminuria data at baseline and at follow-up. Inclusion criteria were known vascular disease or diabetes plus one other cardiovascular risk factor, exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (>1+), and serum creatinine >2.3 mg/dl (200 microM). Baseline microalbuminuria predicted subsequent clinical proteinuria for the study participants overall (adjusted odds ratio [OR], 17.5; 95% confidence interval [CI], 12.6 to 24.4), in participants without diabetes (OR, 16.7; 95% CI, 8.6 to 32.4), and in participants with diabetes (OR, 18.2; 95% CI, 12.4 to 26.7). Any progression of albuminuria (defined as new microalbuminuria or new clinical proteinuria) occurred in 1859 participants; 1542 developed new microalbuminuria, and 317 participants developed clinical proteinuria. Ramipril reduced the risk for any progression (OR, 0.87; 95% CI, 0.78 to 0.97; P = 0.0146). People without and with diabetes who are at high risk for cardiovascular disease are also at risk for a progressive rise in albuminuria. Microalbuminuria itself predicts clinical proteinuria in nondiabetic and in diabetic people. Ramipril prevents or delays the progression of albuminuria.
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PMID:Development of renal disease in people at high cardiovascular risk: results of the HOPE randomized study. 1259 99

Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure. To assess its usefulness in older patients with systolic hypertension and widened pulse pressure, we compared the effects of eplerenone with amlodipine, on clinic blood pressure (BP) and pulse pressure and in a subset of the patients, ambulatory BP, vascular compliance, and urinary albumin excretion. The study involved 269 patients > or =50 years of age who were randomly assigned to either eplerenone (50 to 200 mg daily) or amlodipine (2.5 to 10 mg daily) in a double-blind titration to effect design. After 24 weeks of therapy, reductions in clinic systolic BP were similar for both treatments (eplerenone, -20.5+/-1.1 mm Hg; amlodipine, -20.1+/-1.1 mm Hg). Reductions in clinic diastolic BP were modestly larger on amlodipine (-6.9+/-0.7 mm Hg) compared with eplerenone (-4.5+/-0.7 mm Hg) (P=0.014). Pulse pressure was also reduced similarly from baseline by the 2 treatment groups (eplerenone, -15.9 mm Hg versus amlodipine, -13.4 mm Hg, P=0.07). Changes from baseline in pulse wave velocity after 24 weeks of therapy were statistically similar for eplerenone and amlodipine. In patients with microalbuminuria at baseline (>30 mg albumin/g creatinine), eplerenone reduced the urinary albumin/creatinine ratio by 52% compared with a reduction of 10% by amlodipine (P=0.04). Thus, eplerenone was as effective as amlodipine in lowering systolic BP and pulse pressure as well as pulse wave velocity in older patients with widened pulse pressure hypertension. Furthermore, eplerenone reduced microalbuminuria to a greater extent than amlodipine in this older patient group.
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PMID:Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. 1475 24

Kidney involvement in diabetes mellitus has negative impact on the outcomes of disease. Strong relationship between progressive diabetic kidney disease and the development of other diabetic complications was found by many investigators. In order to evaluate the dynamics of diabetic nephropathy in type I diabetes mellitus during 6-year period and its relationship with other diabetes mellitus complications and control of glycemia and hypertension, in 2002 we reviewed ambulatory case records of patients, who were followed by endocrinologists and who were investigated by us in 1996. During 6-year period, 5.1% from 156 pts. died and all of them had diabetic nephropathy; 26.9% of pts. moved to general practitioners and never visited endocrinologists again. Only 105 pts. remained under follow-up by endocrinologists. Their mean age 37.6+/-1.3 yrs. Out of all patients, 54% were males and 46% females. Mean diabetes mellitus duration was 19.5+/-0.9 yrs. Control of glycaemia was poor and insufficient in 2/3 of pts. HbA(1C) wasn't checked in 68.9% of pts. Control of arterial hypertension became better, but not sufficiently. During 6-year period persistent proteinuria developed in 12.1% of pts., who had no or transient proteinuria <0.5 g/l in 1996. Persistent proteinuria developed 19.9+/-1.8 yrs. after the diabetes mellitus onset and correlated with hypertension and renal insufficiency. Higher level of proteinuria was associated with worse control of glycemia. Progression of diabetic retinopathy and neuropathy over 6 yrs. were more expressed than in diabetic nephropathy. On average retinopathy developed after 14+/-1.8 yrs. after the diabetes mellitus onset, neuropathy--17.8+/-2.2 yrs., renal failure--21.1+/-2.8 yrs., heart failure--22.9+/-1.9 yrs. and arterial hypertension--12.1+/-1.3 yrs. The prevalence and time of incipient diabetic nephropathy appearance remained unknown because the test for microalbuminuria was not available in the primary health care centres.
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PMID:[Dynamics of diabetic nephropathy and other complications of type I diabetes mellitus in the period of 1996-2002 (data from 2 Kaunas outpatient polyclinics)]. 1276 21

Microalbuminuria (defined as an albumin-creatinine ratio of 10-25 mg/mmol on the first-morning urine sample, or an albumin excretion rate of 20-200 microg/min on a timed collection) is present in 20-30% of all patients with type 2 diabetes, and is especially common in those with hypertension, endothelial dysfunction and other features of insulin resistance. Although microalbuminuria is predictive of worsening microvascular disease in the kidney (5-10% per year progress to overt diabetic nephropathy), an increased albumin excretion rate (AER) reflects a generalized abnormality of vascular function and is associated with 2-4-fold increases in cardiovascular and all-cause mortality. The extent to which microalbuminuria is a risk factor independent of other variables in type 2 diabetes, e.g. blood pressure and smoking, has been highlighted by recent cohort studies, e.g. the Heart Outcome Prevention Evaluation study and the Wisconsin Epidemiological Study of Diabetic Retinopathy. In the former study, for example, microalbuminuria at baseline increased the adjusted relative risks (RR) of a major cardiovascular event (RR 1.83), all-cause death (RR 2.09) and hospitalization for heart failure (RR 3.23) in both diabetic and non-diabetic subjects. These studies also highlighted that AER is a continuous risk factor, and that levels of AER below the arbitrary threshold for defining microalbuminuria are associated with relatively increased cardiovascular risk. Similarly, microalbuminuria affects 10-15% of middle-aged non-diabetics and is associated with coronary, peripheral and cerebral vascular complications. Detection of microalbuminuria, especially in type 2 diabetes, signifies the need to intensify blood pressure control as part of a multiple risk factor intervention strategy in a high-risk group. As hypertensive patients with type 2 diabetes are frequently treated by more than one antihypertensive agent, ACE inhibitors and low-dose diuretics are preferably recommended in order to provide sufficient blood pressure control and target organ protection.
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PMID:Microalbuminuria: a common, independent cardiovascular risk factor, especially but not exclusively in type 2 diabetes. 1276 61

Although recent trials have shown that antihypertensive treatment can bring about a reduction in stroke, coronary heart disease, heart failure and renal disease, the situation is no longer improving. This is due to the fact that the percentage of hypertensive patients with satisfactory blood pressure is still very poor. International guidelines on hypertension indicate the importance of assessing the absolute risk of patients and the use of a lower dose of drugs to improve the efficacy-tolerability profile. Diuretics used at lower dosage than in the past are effective in reducing morbidity and mortality and continue to be drugs of first choice in the treatment of hypertension. Indapamide sustained release (Natrilix SR) 1.5 mg has an antihypertensive effect equivalent to indapamide immediate release 2.5 mg with a 50% reduction in incidence of serum potassium levels <3.4 mmol/l. Natrilix SR has proved to have a neutral effect both on lipid and glucose profiles and to reduce microalbuminuria in diabetic hypertensive patients. Recent multicentre European clinical trials have shown that Natrilix SR decreases diastolic blood pressure to <90 mmHg in about 75% of patients treated for 1 year. In elderly patients with isolated systolic hypertension, Natrilix SR has been proven to be as effective as amlodipine 5 mg and significantly more effective than hydrochlorothiazide 25 mg. Natrilix SR produces regression of left ventricular hypertrophy which, in the Left ventricular hypertrophy: Indapamide Versus Enalapril study was greater than that induced by enalapril. Natrilix SR represents an appropriate choice not only as a first-line drug in many hypertensive patients but also in at-risk patients like the elderly, subjects with other cardiovascular risk factors, target organ damage, diabetes, or impaired renal function.
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PMID:Clinical role of Natrilix SR in the treatment of at-risk hypertensive patients. 1276 62


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