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Hypertension plays a critical role in causing a high rate of cardiovascular events in patients with diabetes mellitus. Large trials show that lowering blood pressure in the patient with diabetes who has hypertension has profoundly favorable effects. This review discusses recent trials to answer the question of how low patients' blood pressure should go and which agents should be used to achieve this goal. The National Institutes of Health's guidelines, published in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, call for a blood pressure goal of <130/85 mmHg in patients with diabetes. Based on data from the recent trials, an even lower blood pressure of <130/80 mmHg in patients with diabetes and hypertension appears to be appropriate. Observational studies show that the lowest cardiovascular event rate is observed in patients with diabetes whose systolic blood pressure is <120 mmHg. Thus, goal blood pressure in patients with diabetes who have hypertension may need to be revised lower, to <120/80 mmHg. In patients with overt proteinuria of 1 g/d or more, mean arterial pressure of <92 mmHg is recommended. Available evidence justifies the use of angiotensin-converting enzyme (ACE) inhibitors as first-line agents and angiotensin receptor blockers in those patients who are intolerant to ACE inhibitors. Because the blood pressure goal is lower in patients with diabetes who are hypertensive, these patients require the use of multiple agents. Diuretics or long-acting calcium channel blockers are logical second choices because of their synergistic blood pressure reduction effect observed with ACE inhibitors. Alpha-blockers should be used with caution, however. In patients with renal disease, loop diuretics may be required to reduce sodium and volume overload and to improve blood pressure control.
Cardiol Rev
PMID:Treatment of hypertension in patients with diabetes: lessons from recent trials. 1117 14

The first application of angiotensin converting enzyme (ACE) inhibitors it was the treatment of arterial hypertension. Latter news application appears such as: heart failure, myocardial infarct, nephropathy and diabetic proteinuria. Captopril, the first oral ACE inhibitor was used, since 1986, in the diagnostic screening of renovascular hypertension (RVH). Since then other authors recognised the importance of captopril test in the detection of RVH, advising also it's application in the diagnosis of primary aldosteronism and pheocromocithoma. Based in different publications the sensitivity of captopril test is 40%-100% and the specificity 72%-100%. There are several reasons to explain the differences between these results. In our opinion, these observations appeared as a consequence of the different methodology used. Despite the fact that alternative procedures to captopril test in the screening of RVII do exist this is, in our opinion, the most simple, cheap, safe and efficient test available at the moment.
Rev Port Cardiol 2000 Dec
PMID:[Converting enzyme inhibitors in the diagnosis of secondary arterial hypertension --focus on the captopril test]. 1130 9

CS-866 is a new angiotensin II receptor blocker that has demonstrated effectiveness for lowering blood pressure in animal models of hypertension. Given the proposed involvement of the renin-angiotensin system in diabetic nephropathy and atherosclerosis, we have tested CS-866 in animal models of these conditions. The renal protective properties of CS-866 were examined in the Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes that develops progressive hyperglycemia, glomerulosclerosis, and proteinuria. Treatment of ZDF rats with CS-866 in the diet for 19 weeks resulted in a dose-dependent reduction in urinary protein excretion compared with vehicle-treated control rats, which was independent of changes in blood pressure and glycemic state. The antiatherosclerotic properties of CS-866 were tested in 2 animal models. In the first study, cynomolgus monkeys were fed a high-cholesterol diet for 6 months while receiving CS-866 or vehicle. At the end of this period, CS-866-treated animals had 64% less plaque area in the aorta than controls. CS-866 was also tested in the Watanabe heritable hyperlipidemic (WHHL) rabbit model of atherosclerosis. WHHL rabbits were treated for 32 weeks with CS-866 (1 mg/kg), pravastatin (50 mg/kg), a combination of the 2 drugs, or vehicle. CS-866 had no effect on plasma cholesterol levels and reduced blood pressures minimally. Pravastatin alone reduced serum cholesterol but had no effect on blood pressure or lesion area. In contrast, treatment with CS-866 resulted in a 40% reduction in lesion area compared with vehicle-treated control when given alone and a 50% reduction in combination with pravastatin. On the basis of results from animal models, CS-866 may be a useful treatment for diabetic nephropathy and atherosclerosis.
Am J Cardiol 2001 Apr 19
PMID:New pharmacologic aspects of CS-866, the newest angiotensin II receptor antagonist. 1133 66

Initial pharmacologic therapy for hypertension is low-dose thiazide diuretics, beta-blockers, and ACE inhibitors. Increasing data have confirmed that ACE inhibitors have specific benefit in patients with diabetes, atherosclerosis, left ventricular dysfunction, and renal insufficiency. CCBs are alternative agents for ISH in the elderly and appear to decrease stroke with perhaps less protection against progression of renal insufficiency and proteinuria, CAD mortality and new onset heart failure versus other initial agents, especially ACE inhibitors. ARBs are well tolerated and effective blood pressure lowering agents but have not been confirmed as effective as ACE inhibitors for reducing renal progression, clinical events, or mortality from heart failure. Effective pharmacologic antihypertensive therapy may avoid disabling and undetected cerebrovascular disease, cognitive dysfunction, and disturbing symptoms of elevated blood pressure. Vasopeptidase inhibitor, such as omapatrilat, and endothelin-1 antagonist, such as bosentan, may become future agents approved for the reduction of morbidity and mortality with hypertension. The ALLHAT trial continues to examine the potential benefits and harms of amlodipine versus chlorthalidone and lisinopril in a diverse high-risk population. Based on ALLHAT data, however, doxazosin is no longer an acceptable initial pharmacological agent. Intensive pharmacologic treatment with blood pressure lowering to less than 130/85 mm Hg is recommended with diabetes, renal insufficiency, and heart failure with additional goal of less than 125/75 mm Hg with renal failure and proteinuria greater than 1 g/24 h, based on multiple outcome studies.
Cardiol Clin 2001 May
PMID:Update in pharmacologic treatment of hypertension. 1140 10

The angiotensin-converting enzyme inhibitor, perindopril erbumine, has been approved for use in the United States only recently but has been studied extensively worldwide over the last decade. Placebo-controlled trials in a wide range of patients with hypertension, including the elderly, those with isolated systolic hypertension, and those with concomitant diseases such as hyperlipidemia, diabetes, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, and chronic obstructive pulmonary disease, have shown that perindopril is highly effective in lowering both systolic and diastolic blood pressure (BP). Studies in which BP has been monitored for 24-hour intervals show that perindopril (1) has a gradual onset of action, (2) provides smooth BP control over its once-daily dosing interval, (3) has a trough-peak ratio of about 1, and (4) maintains its antihypertensive efficacy despite missed doses. Perindopril increases arterial compliance and reverses left ventricular hypertrophy in hypertensive patients. Both of these effects are at least partly independent of its ability to lower BP. Perindopril is safe and well tolerated in patients with hypertension. Rates of adverse events and discontinuation because of such events are low.
Am J Cardiol 2001 Oct 04
PMID:Efficacy of perindopril in the treatment of systemic hypertension. 1159 55

Approximately 25% of US adults have high blood pressure (BP). Selection of effective and safe antihypertensive therapy for these individuals is an important health-care priority. High BP can be treated with a wide range of antihypertensive agents from a number of different classes. These drugs may differ in their suitability for administration to different subpopulations of patients. Results from both clinical trials and postmarketing surveillance indicate that the angiotensin-converting enzyme (ACE) inhibitor perindopril erbumine is safe and well tolerated in a wide range of patients with hypertension. Cough, the most common ACE inhibitor-associated side effect, is also the most common clinical adverse event reported for perindopril, but <2% of perindopril-treated patients discontinue therapy because of cough. Other adverse events often associated with ACE inhibitors, first-dose hypotension and hyperkalemia, appear to occur less often with perindopril than with other agents in this class. The favorable safety profile for perindopril extends to a wide range of patients, including the elderly and those with either heart failure or renal disease. Perindopril has no negative effects on lipids in patients with hyperlipidemia or on glycemic control in patients with type 2 diabetes mellitus, and it reduces proteinuria in patients with renal disease. Perindopril has no known clinically significant drug-drug interactions. Thus, perindopril is a safe BP-lowering agent with documented tolerability in a wide range of patients with hypertension.
Am J Cardiol 2001 Oct 04
PMID:Safety profile of perindopril. 1159 59

The presence of an altered renal function in essential hypertension, advanced heart failure (HF) and after a myocardial infarction (MI) is associated with higher cardiovascular morbidity and mortality. Indices of altered renal function (e.g., microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance or overt proteinuria) are independent predictors of cardiovascular morbidity and mortality in any of the three clinical situations. These parameters should then be routinely evaluated in clinical practice. These facts have several therapeutic implications. First, although there is no evidence-based information on the level of blood pressure that confers optimal renal protection, levels substantially lower than past recommendations are advisable. Second, hypertensive kidney damage should be prevented by early treatment of hypertensive patients, particularly those with microalbuminuria. Finally, to avoid further aggravation of high cardiovascular risk, antihypertensive agents devoid of unwanted metabolic side effects should be used for the treatment of hypertensive vascular damage. In HF, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker seem to be the most renoprotective. Renal outcome is also improved by ACE inhibition after an MI. Finally, renal and cardiovascular outcome seem to run in parallel in all these situations.
J Am Coll Cardiol 2001 Dec
PMID:Renal function: the Cinderella of cardiovascular risk profile. 1173 74

A number of studies have demonstrated a beneficial effect of regular physical activity on levels of HgbA(1)C in patients with type II diabetes mellitus, largely due to an increase in insulin sensitivity. Benefits are related to short-term improvements in insulin sensitivity following individual exercise bouts. Regular exercise can prevent or delay the onset of type II diabetes in high-risk populations. The insulin resistant state is associated with a cluster of cardiovascular risk factors all of which improve with regular physical activity. Because of the high incidence of occult coronary disease, patients need a cardiovascular evaluation when initiating an exercise program. High intensity exercise may result in retinal hemorrhage and transient worsening of diabetic proteinuria. The most common complication is hypoglycemia. A combination of aerobic and light resistance exercise is appropriate. Patients should exercise a minimum of three times a week for 30-60 minutes at 50% to 75% of their VO(2max). (c) 2000 by CHF, Inc.
Prev Cardiol 2000
PMID:The role of exercise in type II diabetes mellitus. 1183 22

We review the mechanisms by which arterial hypertension induces target organs damage, particularly the heart, kidney, and vascular endothelium, which is manifested as ventricular hypertrophy, proteinuria, and renal failure and endothelial dysfunction. Furthermore, the effect of antihypertensive treatment in these situations is analyzed. Experimental and clinical studies show that angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor antagonist drugs are more efficient than other antihypertensive treatments in the reversal of left ventricular hypertrophy and proteinuria, in delaying kidney damage and improving of endothelial function.
Arch Cardiol Mex
PMID:[Impact of antihypertensive treatment on target organs]. 1200 72

Changes in renal function produced by hypertension appear to be associated with higher cardiovascular morbidity and mortality. Indices of altered renal function (eg, microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance, or overt proteinuria) are independent predictors of cardiovascular morbidity and mortality. The Framingham Heart Study documented the relevance of proteinuria for cardiovascular prognosis in the community. The International Nifedipine GITS study: Intervention as a goal in Hypertension Treatment (INSIGHT) study assessed the role of proteinuria as a very powerful risk factor. Several studies demonstrated that microalbuminuria is a predictor of cardiovascular disease. It has been shown that the presence of microalbuminuria in primary hypertension carries an elevated cardiovascular risk. Furthermore, recent data indicate that even minor derangements of renal function are associated with an increase in cardiovascular risk factors, and promote progression of atherosclerosis. All these parameters should routinely be evaluated in clinical practice, and in the future must be considered in any stratification of cardiovascular risk in hypertensive patients.
Curr Cardiol Rep 2002 Nov
PMID:Proteinuria: an underappreciated risk factor in cardiovascular disease. 1237 63


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