Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension, left ventricular hypertrophy (LVH), hypercreatininemia, and microalbuminuria (MA) are independent risk factors for cardiovascular disease (CVD). Hypertension increases the risk of CVD by two- to three-fold and LVH (especially concentric) is a risk factor for coronary heart disease, heart failure, stroke, and peripheral arterial disease. In people with hypertension, a serum creatinine level of 1.7 mg/dL or more may be an even stronger CVD risk factor than diabetes, smoking, LVH, or systolic blood pressure. Similarly, MA is a strong and independent predictor of CVD morbidity and mortality in people with and without diabetes and/or hypertension. Impaired renal sodium handling and sodium retention are physiological hallmarks of the very early stages of heart failure. Heart failure is a physiologically delicate condition that can decompensate with excess dietary salt intake or over diuresis, or compensate with cautious therapy designed to block the sodium retention and simultaneously interrupt excessively activated neurohumoral mechanisms.
 ...
PMID:Abnormalities of kidney function as a cause and a consequence of cardiovascular disease. 1010 Jun 91

The elevation of systolic blood pressure associated with aging has been considered for years a physiologic phenomenon. This idea was based on the repeated observation that, also after middle age, a large majority of individuals in industrialized countries experience a continuous and progressive increase over time in systolic blood pressure, not in diastolic blood pressure. However, some individuals in industrialized countries and most individuals in nonindustrialized countries do not acquire an increased systolic blood pressure over time proving that the age-associated rise in systolic blood pressure is not an inevitable phenomenon. The change in systolic blood pressure over time strongly reflects lifestyles. Diet-dependent factors such as body weight, alcohol intake, and balance between dietary salt and potassium, are important in favoring the age-associated increase in systolic blood pressure, independently of several confounders. Epidemiologic studies suggest that elevation of systolic blood pressure is a risk factor for cardiovascular diseases: it relates to high incidence of lethal and nonlethal cardiovascular events also in the presence of diastolic blood pressure in the nonhypertensive range. Controlled clinical trials show that the treatment of isolated systolic hypertension reduces the number of cardiovascular events. In addition to cardiovascular disease, systolic blood pressure relates also to microalbuminuria, an index of early glomerular damage, to long-term incidence of end-stage renal disease, and, in hemodialyzed patients, to premature death. Thus, high systolic blood pressure appears an unhealthy condition also for patients with or at risk for kidney diseases.
 ...
PMID:Systolic hypertension: the nephrologist's point of view. 1020 63

A connection between salt sensitivity and hypertension seems certain, but a number of issues remain unresolved, e.g., the mechanisms involved in salt sensitivity, its role in pathogenesis and/or maintenance of hypertension, and its ability to predict cardiorenal risk. The role of nitric oxide (NO) has been studied extensively. Evidence shows that NO, along with the vasoactive substances angiotensin II and endothelin-1, is important in modulating vascular tone. In addition, imbalances among these substances may participate in the abnormal cardiovascular and renal remodeling that occurs in hypertension. What causes such imbalances remains unclear. Animal studies show that in salt-sensitive subjects, the activity of NO synthase (NOS) fails to upregulate in response to increases in blood pressure, but that such activity upregulates rapidly in similar circumstances in non-salt-sensitive subjects. Human studies of essential hypertensives have shown an association between salt sensitivity and a number of conditions, including impaired endothelium-dependent relaxation mediated by NO, insulin resistance, microalbuminuria, and ventricular hypertrophy and cardiovascular events. These findings have intriguing implications in regard to whether, in hypertension, salt sensitivity might be a marker of increased cardiovascular and renal risk that is linked to abnormalities in the bioactivity of NO.
 ...
PMID:Nitric oxide, salt sensitivity, and cardiorenal injury in hypertension. 1022 36

The objective of the present study was to analyze the influence of the I/D polymorphism of the ACE gene on the outcome of microalbuminuria in essential hypertensive patients who were receiving antihypertensive treatment. One hundred thirty-six essential hypertensive patients who were <50 years old and had never previously received treatment with antihypertensive drugs were included in the study. During a 3-year period, patients received nonpharmacological treatment consisting of moderate salt restriction and a low-calorie diet they were obese, with or without a regimen of antihypertensive drugs based on beta-blockers or ACE inhibitors. Hydrochlorothiazide was added when necessary to maintain the blood pressure goal of <135/85 mm Hg. At the beginning of the study and at yearly intervals, systolic and diastolic blood pressures (SBP and DBP, respectively), 24-hour urinary albumin excretion (UAE), renal function, and biochemical profile measurements were made. The insertion/deletion (I/D) polymorphism of the ACE gene was determined through the use of polymerase chain reaction. The variables used in the statistical analysis were the measurements at the start of the study and the increase or decrease detected during the follow-up, estimated as individual specific regression line slope values. At baseline, no differences in blood pressure or UAE values were observed among genotypes. Likewise, the genotype or allele frequency was not significantly different between normoalbuminurics and microalbuminurics. After the 3 treatment years, significant reductions in SBP, DBP, and UAE were found (SBP 151.6+/-17.3 reduced to 137.2+/-14.3 mm Hg, P<0.001; DBP 96.6+/-8.9 reduced to 84.5+/-9.8 mm Hg, P<0.001; UAE 36.7+/-71.5 reduced to 28.3+/-78.6 mg/24 h, P<0. 05). The slopes of these parameters over time did not differ significantly among genotypes. The slope of SBP was the main factor related to the slope of logUAE (P<0.003). A significant positive correlation coefficient between the SBP and logUAE slopes was observed for the DD patients (r=0.57, P<0.0001) but was absent in patients carrying the I allele (II r=-0.03, P=NS; I/D r=0.01, P=NS). Follow-up studies should be used to achieve a better understanding of the impact of candidate gene polymorphisms on the development of hypertension-induced organ damage. Assessment of the I/D polymorphism of the ACE gene may identify subjects who require a greatly lowered blood pressure to prevent organ damage and to reduce hypertension-associated complications and death.
 ...
PMID:Influence of the I/D polymorphism of the angiotensin-converting enzyme gene on the outcome of microalbuminuria in essential hypertension. 1064 47

The combination of obesity with arterial hypertension is frequent finding in clinical practice. In 70% of the males and 61% of the females the high blood pressure is directly connected with obesity. The assumed mechanisms by which obesity leads to arterial hypertension are: insuline resistance; genetic factors (hypothesis for the sparing gene); correlations leptin-neuropeptide Y; fatty tissue as origin of local pressor and depressor humoral factors. The arterial hypertension in obesity is salt-sensible, associated with increased intraglomerular pressure, microalbuminuria and increased risk for cardiovascular complications. The reduction of the body weight is the principal nonmedical mean for treatment of the arterial hypertension. Of the antihypertensive drugs those which are neutral with respect to the carbohydrat and fat metabolism are preferred inhibitors of the converting enzyme, calcium antagonists, selective alpha-1 blockers, central alpha-2 agonist.
 ...
PMID:[Arterial hypertension and obesity--a dangerous combination]. 1084 46

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
 ...
PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

Adrenomedullin (ADM) infusion increases salt excretion in the rat. However, there is no evidence that this substance is related to changes in salt intake in humans. In this study we sought whether the urinary excretion rate of this autacoid is related to salt intake and by the expected changes in arterial pressure in patients with mild essential hypertension. The influence of salt intake on the renal excretion of ADM was investigated in 55 hypertensive patients in a double blind, randomized and crossover study comparing a 2-week 50 mmol/day salt intake period with a 150 mmol/day salt intake period. Twenty-four-hour ADM and endothelin-1 (ET-1) excretion rate were measured by radioimmunoassay on preextracted urinary samples (intraassay confidence variable <8%). The antibodies used in these assays had minimal ADM-ET-1 cross-reactivity (<1%). Twenty-four-hour microalbuminuria was measured by nephelometry. On univariate analysis changes in urinary ADM were significantly related to those in salt excretion (r = 0.33, P = .01) as well as to changes in urinary ET-1 (r = 0.56, P = .0001). Furthermore, changes in urinary albumin excretion were related to those in urinary ET-1 (r = 0.26, P = .05), but were independent of those in urinary ADM (P = .19). In a multiple regression model including age, sex, body mass index, and changes in systolic pressure, plasma renin activity and plasma aldosterone and urine volume, salt excretion resulted as the stronger independent predictor of urinary ADM (r = 0.33, P = .01). However, changes in urinary salt lost prediction power (P = .11) for urinary ADM when urinary ET-1 was introduced into the model. In this model (multiple r = 0.31) urinary ET-1 resulted to be the only independent predictor of urinary ADM (beta = 0.56, P = .0001). This study is the first to show that the renal excretion of ADM is related to changes in salt intake and that it is tightly linked to that of ET-1. The data support the notion that these autacoids play a role in the regulation of sodium metabolism in patients with mild hypertension. The intercorrelations between ET-1, ADM, and microalbuminuria are compatible with the hypothesis that ET-1 is involved in a salt-induced increase in glomerular pressure and suggest that ADM may act as a counterregulatory factor in this situation.
 ...
PMID:Urinary adrenomedullin is related to ET-1 and salt intake in patients with mild essential hypertension. Salt Sensitivity Group of Italian Society of Hypertension. 1128 Dec 33

Microalbuminuria (MA) is defined as persistent elevation of albumin in the urine, of 30-300 mg/day (20-200 microg/min). These values are less than the values detected by routine urine dipstick testing, which does not become positive until protein excretion exceeds 300-500 mg/day. Use of the albumin-to-creatinine ratio is recommended as the preferred screening strategy for all diabetic patients. MA is measured in spot morning urine obtained from the patient in the office and sent for measurement of both albumin and creatinine. A value above 0.03 mg/mg suggests that albumin excretion is above 30 mg/day and therefore MA is present. MA should be checked annually in everyone, and every 6 months within the first year of treatment to assess the impact in patients started on antihypertensive therapy. MA is an established risk factor for renal disease progression in type 1 diabetes and its presence is the earliest clinical sign of diabetic nephropathy. In addition, a number of studies suggest that MA is an important risk factor for cardiovascular disease and defines a group at high risk for early cardiovascular mortality in both type 2 diabetes and essential hypertension. MA also signifies abnormal vascular permeability and the presence of atherosclerosis. Among nondiabetic patients with essential hypertension, MA is associated with higher blood pressures, increased serum total cholesterol, and reduced serum high-density lipoprotein cholesterol. Thus, taken together these data support the concept that the presence of MA is the kidney's notice to the physician/patient that there is a problem with the vasculature. MA can be reduced, and progression to overt proteinuria prevented, by aggressive blood pressure reduction. The National Kidney Foundation recommends that blood pressure levels be maintained at or below 130/80 mm Hg in anyone with diabetes or renal disease. This should be accomplished with antihypertensive agents that prevent the rise in MA and hence prevent development of proteinuria. Such agents are angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and, to a lesser extent, Beta blockers, non-dihydropyridine calcium antagonists, and diuretics. In summary, the presence of MA is a marker of endothelial dysfunction and a harbinger of markedly enhanced cardiovascular risk. All patients with diabetes and/or hypertension should be screened for the presence of microalbuminuria with use of spot morning urine. To maximize prevention of MA development, the following goals should be instituted: 1) blood pressure should be maintained at less than 130/80 mm Hg and a low-salt, moderate-potassium diet instituted; 2) in diabetics, HbA1c should be kept at less than 7%; 3) in obese patients, a weight loss program should be implemented, with a goal BMI of less than 30; and 4) the physician and patient, working together, should maintain low-density lipoprotein cholesterol at less than 120 mg/dL, and less than 100 mg/dL if diabetes is present. (c)2001 by Le Jacq Communications, Inc.
 ...
PMID:Microalbuminuria: what is it? Why is it important? What should be done about it? 1141 91

Psychological stress has been reported to be related to higher blood pressure (BP) and unfavorable cardiovascular profile. However, because of the complexity of personal stress management, a multilevel stress measurement strategy is needed. The aim of this cross-sectional study was to analyze the respective influences of the subjective perception of professional strain (high demand and low latitude) and cardiovascular reactivity to a stress test (Stroop stress test) on BP. Worksite BP was measured in 303 healthy normotensive subjects, 18 to 55 years of age, who worked in the same chemical company. In a subset of 70 randomly selected subjects, 24-hour ambulatory BP was performed to assess BP during working hours. The 20% of subjects who reported the highest job strain (high-strain group) or the highest BP stress reactivity (high-responder group) were compared with the remaining subjects (80%) (non-high-strain or low-responder groups). Subjects who submitted to the highest job strain had significantly higher ambulatory diastolic BP (4.5 mm Hg, P=0.015) during only working hours, whereas BP was similar during the remaining hours. Worksite BP and stress cardiovascular reactivity were similar between job strain groups. BP stress reactivity did not influence worksite and ambulatory BP. Spontaneous BP variability assessed by standard deviation and spectral analysis was equivalent between complementary groups. Prevalence of microalbuminuria was significantly higher in the high-responder group (8.2% versus 2.5% in low responders) and only slightly higher in the high-strain group (6.2% versus 3.2% in non-high strain). Potential confounding factors, such as age, gender, alcohol consumption, salt intake, body mass index, and occupation, which were equivalent between groups, did not interfere with our results. Our study quantifies high-professional strain effects on BP levels that appear to be higher only during the working period and to be independent from spontaneous BP variability and stress BP reactivity.
 ...
PMID:Perceived job stress but not individual cardiovascular reactivity to stress is related to higher blood pressure at work. 1146 62

The possible influence of dietary components on the progression or regression of microalbuminuria (MA) in type 1 diabetic patients was investigated prospectively over 5 years. The dietary intake of 47 patients with type 1 diabetes and MA (20-200 micrograms/min.), well instructed in diabetes management was observed in bimonthly intervals. Accuracy of 4-day diet protocols was verified by comparing the amount of documented protein intake with the measured nitrogen excretion. Non compliance was defined as deviation more than 30% between both values. These patients were eliminated from the study. Data from 37 patients with good compliance over a 5 year period have been used for multiple stepwise regression analysis. Taking into consideration Body mass index (BMI), blood pressure, HbA1c and time, MA was used as dependent variable, 16 dietary variables with a bivariate significance p < 0.05 as independent variables. The regression analysis (R2 = 0.589, p = 0.0015) showed clear associations between MA and the amount of salt intake (beta = 0.683, p < 0.002), saturated fatty acids (beta = 0.342, p = 0.029) and the amount of consumed mono- and disaccharides (beta = 0.479, p = 0.018). There was no significant association with the amount of protein intake (beta = 0.319, p = 0.152). Looking at the fatty acids in particular there were significant associations to MA with myristic acid, arachidonic acid and negatively with linoleic acid. Splitting the data in tertiles according to the amount of salt intake (I: < 6 g/d, II: 6-10 g/d, III: > 10 g/d) we could show in addition to the overall effect an intraindividual influence on the amount of MA (MA-means +/- SD: I: 45 +/- 56 micrograms/min., II: 61 +/- 59, III: 81 +/- 74, p < 0.001 between the groups). There were no significant differences between the groups in mean blood pressure, HbA1c and BMI.
 ...
PMID:[Effect of nutrition on microalbuminuria in patients with type 1 diabetes: prospective data evaluation over 5 years]. 1151 95


<< Previous 1 2 3 4 5 6 Next >>