Relation between albumin in the urine and electrocardiographic markers of myocardial ischemia in patients without diabetes mellitus.
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Adult↗
Biomedical subjects
W M Janssen
Publications and source records attributed to W M Janssen.
Oral contraceptive use and hormone replacement therapy are associated with microalbuminuria.
BACKGROUND: Controversy exists regarding the adverse and beneficial effects of oral contraceptive use and hormone replacement therapy. Microalbuminuria is associated with increased risk of renal and cardiovascular disease. OBJECTIVE: To examine the association between oral contraceptive use or hormone replacement therapy and microalbuminuria. METHODS: We performed a case-control study of the baseline data and historical pharmacy data of 4301 female subjects of the Prevention of Renal and Vascular End Stage Disease study cohort, aged 28 to 75 years, excluding women who were pregnant or had type 1 diabetes mellitus. The main outcome measure was microalbuminuria, defined as a urinary albumin excretion of 30 to 300 mg per 24 hours (recorded as the mean of two 24-hour urine collections). RESULTS: After adjusting for age, hypertension, diabetes, obesity, hyperlipidemia, and smoking, the odds ratio (OR) for having microalbuminuria was 1.90 (95% confidence interval [CI], 1.23-2.93) for premenopausal oral contraceptive users and 2.05 (95% CI, 1.12-3.77) for postmenopausal hormone replacement therapy users. The point estimate increased in a dose-dependent fashion, albeit insignificantly, according to the estrogen content of the oral contraceptives (<30 microg ethinyl estradiol: OR, 1.11; 95% CI, 0.14-8.56; 30 to <50 microg: OR, 1.83; 95% CI, 1.17-2.87; and 50 microg: OR, 2.72; 95% CI, 0.81-9.08). The OR was greater in oral contraceptives with a second-generation (OR, 2.04; 95% CI, 1.28-3.25) vs a third-generation progestin (OR, 1.39; 95% CI, 0.63-3.06). The OR increased with the duration of hormone replacement therapy (< or =5 years, OR, 1.28; 95% CI, 0.37-4.50; >5 years, OR, 2.56; 95% CI, 1.32-4.97). CONCLUSION: Regular and long-term oral contraceptive use and hormone replacement therapy are associated with an increased risk for microalbuminuria and cardiovascular disease.
Adult↗
Excessive urinary albumin levels are associated with future cardiovascular mortality in postmenopausal women.
BACKGROUND: Microalbuminuria is an early predictor of cardiovascular morbidity and mortality, in both diabetic patients and hypertensive patients. Little is known about the relation of microalbuminuria to cardiovascular disease in women of the general population. METHODS AND RESULTS: We have studied the relation of urinary albumin levels to cardiovascular mortality in a cohort study of 12 239 postmenopausal women living in Utrecht, the Netherlands. The initial age was between 52 and 67 years. Women were followed on vital status between 1976 and 1995 (168 513 women-years). Albumin was determined in the urine of 561 cases and 557 controls. Data were analyzed by using a nested case-control design. The cardiovascular mortality rate (95% CI) for women who were in the highest quintile of urinary albumin levels was 13.2/1000 years (8.1 to 20.9) compared with 2.6/1000 years (2.3 to 3.1) in women without detectable urinary albumin. The age-adjusted rate ratio (95% CI) between these groups was 4.4 (2.6 to 7.6). CONCLUSIONS: This is the first large cohort study that confirms a predictive role of urinary albumin for the risk of future cardiovascular mortality independent of hypertension and diabetes. Our findings support the hypothesis that microalbuminuria is a reflection of vascular damage and a marker of early arterial disease in women from the general population.
Age Factors↗
Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity.
OBJECTIVES: To assess the prevalence of microalbuminuria in the general population, especially in nondiabetic and nonhypertensive subjects, and its association with known cardiovascular risk factors and cardiovascular morbidity. DESIGN: Cross-sectional cohort study. SETTING: Inhabitants of the city of Groningen, the Netherlands. SUBJECTS: All inhabitants, aged between 28 and 75 years, were send a postal questionnaire and a vial to collect an early morning urine sample (n = 85 421). Of these 40 856 subjects (47.8%) responded. Cardiovascular risk factors and morbidity were validated in a well defined nondiabetic and nonhypertensive group of 5241 subjects. MAIN OUTCOME MEASURES: Microalbuminuria, self-reported cardiovascular risk and cardiovascular morbidity in the total study cohort, and additionally more detailed measurements in a subset of the total population. RESULTS: Microalbuminuria (20-200 mg L-1) was present in 7.2% of the subjects and independently associated with age, gender, hypertension, diabetes, smoking, previous myocardial infarction and stroke. Some of these associations were already observed at albuminuria levels of 10-20 mg L-1. After exclusion of the diabetic and hypertensive subjects, microalbuminuria was still prevalent in 6.6% of the subjects. CONCLUSIONS: Microalbuminuria appears to be common not only in the general population but also in a nondiabetic, nonhypertensive population and is independently associated with increased cardiovascular risk factors and cardio-vascular morbidity. Importantly, some of these associations are present at urinary albumin levels currently considered to be normal. These findings suggest that urinary albumin measurements may be useful in early risk profiling and prevention of cardiovascular disease in the population at large.
Adult↗
[Psychosocial consequences of screening for microalbuminuria and for some other risk factors].
OBJECTIVE: Obtaining insight into the psychosocial consequences of a screening programme for the progression of heart, vessel and kidney damage. DESIGN: Questionnaire investigation. METHOD: This study addressed participants in the 'Prevention of renal and vascular end-stage disease' (PREVEND) study, which included about 40,000 inhabitants of Groningen, the Netherlands, aged 28-75 years, who were asked to send in a vial with morning urine in order to detect microalbuminuria. People with microalbuminuria were invited to a general practitioners' laboratory to determine the risk factors: urinary protein concentration, blood pressure and blood cholesterol level. A questionnaire was sent to 335 participants of the screening who had received the screening results two weeks before. RESULTS: The response rate was 75%. A minority of the respondents diagnosed with risk factors, expressed some concern. No influence on the wellbeing of this group of participants was established. Almost one-third of the respondents stated that they now 'lived according to healthier principles' because of the screening. On the other hand, there was a certain 'certificate of health effect': about half the smokers and the physically inactive saw the favourable screening result as a legitimation for their life style. An unfavourable screening result had led to additional medical consumption in almost half the respondents. The respondents appreciated the screening and especially the lower-educated had a very positive attitude towards early diagnosis in general. CONCLUSION: The screening positives showed no diminished wellbeing; their health behaviour improved due to the screening and they had a higher medical consumption. About half the screening negatives regarded the results as a legitimation of their unhealthy life style.
Adult↗
Smoking is related to albuminuria and abnormal renal function in nondiabetic persons.
BACKGROUND: Smoking induces albuminuria and accelerates progression to renal failure in persons with diabetes, but little is known about the relation between smoking and renal function in nondiabetic persons. OBJECTIVE: To investigate whether smoking is related to albuminuria and abnormal renal function in nondiabetic persons. DESIGN: Cross-sectional study. SETTING: Groningen, The Netherlands. PARTICIPANTS: 7476 participants in the PREVEND (Prevention of REnal and Vascular ENd stage Disease) Study. MEASUREMENTS: Microalbuminuria and high normal albuminuria were defined as urinary albumin excretion of 30 to 300 mg/24 h and 15 to 30 mg/24 h, respectively. Elevated or decreased glomerular filtration rate (GFR) was defined as a creatinine clearance that exceeded or was less than two times the standard deviation of the mean value in nondiabetic, nonsmoking participants who had an albumin excretion of 0 to 15 mg/24 h, adjusted for age and sex. RESULTS: Current smokers had a higher median albumin excretion than nonsmokers and were more likely to have microalbuminuria and high normal albuminuria with elevated or decreased GFR. After adjustment for several potential confounding factors, persons who smoked 20 or fewer cigarettes/d and persons who smoked more than 20 cigarettes/d, respectively, showed a dose-dependent association between smoking and high normal albuminuria (relative risk, 1.33 [95% CI, 1.10 to 1.61] and 1.98 [CI, 1.49 to 2.64]), microalbuminuria (relative risk, 1.92 [CI, 1.54 to 2.39] and 2.15 [CI, 1.52 to 3.03]), elevated GFR (relative risk, 1. 82 [CI, 1.31 to 2.53] and 1.84 [CI, 1.12 to 3.02]), and decreased GFR (relative risk, 1.53 [CI, 1.04 to 2.24] and 1.83 [CI, 1.05 to 3. 20]), respectively. Quitting smoking was associated only with microalbuminuria. CONCLUSIONS: Smoking is associated with albuminuria and abnormal renal function. However, these associations are less pronounced or absent in former smokers.
Adult↗
Rationale, design, and baseline characteristics of a trial of prevention of cardiovascular and renal disease with fosinopril and pravastatin in nonhypertensive, nonhypercholesterolemic subjects with microalbuminuria (the Prevention of REnal and Vascular ENdstage Disease Intervention Trial [PREVEND IT]).
This study describes the rationale, design, and baseline characteristics of a trial to determine whether treatment with fosinopril 20 mg/day and/or pravastatin 40 mg/ day will prevent cardiovascular and renal disease in nonhypertensive (RR <160/100 mm Hg and not using antihypertensive medication) and nonhypercholesterolemic (total cholesterol <8.0 or <5.0 mmol/L in case of previous myocardial infarction and not using lipid lowering medication) men and women with persistent microalbuminuria (urinary albumin excretion >10 mg/L once in an early morning spot urine and 15 to 300 mg/24-hour at least once in two 24-hour urine collections). The Prevention of REnal and Vascular ENdstage Disease Intervention Trial is a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design. The 864 randomized subjects will be monitored for a minimum of 4 years and a maximum of 5 years. The primary efficacy parameter is defined as the combined incidence of all-cause mortality or hospital admission for documented (1) nonfatal myocardial infarction, (2) myocardial ischemia, (3) heart failure, (4) peripheral vascular disease, (5) cerebrovascular accident and/or (6) end-stage renal disease.
Adult↗
Microalbuminuria is independently associated with ischaemic electrocardiographic abnormalities in a large non-diabetic population. The PREVEND (Prevention of REnal and Vascular ENdstage Disease) study.
AIM: To assess the value of microalbuminuria as an indicator of increased cardiovascular risk in a non-diabetic population. METHODS AND RESULTS: 7579 non-diabetic subjects were studied with ages ranging from 28 to 75 years selected from a population based cohort. Using computerized Minnesota coding, ischaemic electrocardiographic abnormalities were divided into three categories: infarct patterns, major ischaemia, and minor ischaemia. Urinary albumin excretion was measured as the mean of two 24-h urine collections. Cardiovascular risk indicators were defined as an age above 60 years, male sex, hypertension, hypercholesterolaemia, smoking, obesity and a positive cardiovascular family history. Microalbuminuria was associated with age, sex, blood pressure, serum cholesterol, serum glucose, body mass index and all three categories of electrocardiographic abnormalities. In a multivariate model, adjusted for established cardiovascular risk indicators, microalbuminuria was independently associated with infarct patterns (OR [95% CI] 1.61 [1.12-2.32]), major ischaemia (OR 1.43 [1.08-1.91]) and minor ischaemia (OR 1.32 [1.03-1.68]). CONCLUSIONS: The independent association between microalbuminuria and ischaemic electrocardiographic abnormalities suggests that microalbuminuria has additional value to conventional risk indicators in predicting cardiovascular disease in non-diabetics. Assessment of microalbuminuria could be an instrument to identify those at an increased risk for coronary vascular disease in an early stage.
Adult↗
Low levels of urinary albumin excretion are associated with cardiovascular risk factors in the general population.
Microalbuminuria is associated with both an increased prevalence of cardiovascular risk factors and greater renal and cardiovascular morbidity. We questioned whether in the general population such associations can be found at lower levels of urinary albumin excretion than that of classically defined microalbuminuria. To that purpose urinary albumin concentration was measured in 40619 subjects aged 28 to 75 years. The subjects filled in a questionnaire on cardiovascular risk factors and events and were divided in deciles according to their urinary albumin concentration. Smoking was associated with albuminuria in the fifth or higher decile of urinary albumin concentration, that is with an albumin concentration of 5.1 mg/l and higher. The lower cut-off point for a positive association with hypertension was 8.8 mg/l, and for diabetes 11.2 mg/l. Family history for cardiovascular disease and hyperlipidaemia were not associated with albuminuria. We conclude that urinary albumin concentrations far below the microalbuminuric range are associated with increased prevalence of established cardiovascular risk factors. Family history for cardiovascular disease and hyperlipidaemia seems to behave differently. These data emphasize the need for more studies on the impact of albuminuria on the prediction of cardiovascular and renal disease in the general population.
Adult↗
Inadequate management of blood pressure in a hypertensive population.
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Adult↗
Pyruvate decarboxylase: an indispensable enzyme for growth of Saccharomyces cerevisiae on glucose.
In Saccharomyces cerevisiae, the structural genes PDC1, PDC5 and PDC6 each encode an active pyruvate decarboxylase. Replacement mutations in these genes were introduced in a homothallic wild-type strain, using the dominant marker genes APT1 and Tn5ble. A pyruvate-decarboxylase-negative (Pdc-) mutant lacking all three PDC genes exhibited a three-fold lower growth rate in complex medium with glucose than the isogenic wild-type strain. Growth in batch cultures on complex and defined media with ethanol was not impaired in Pdc- strains. Furthermore, in ethanol-limited chemostat cultures, the biomass yield of Pdc- and wild-type S. cerevisiae were identical. However, Pdc- S. cerevisiae was unable to grow in batch cultures on a defined mineral medium with glucose as the sole carbon source. When aerobic, ethanol-limited chemostat cultures (D = 0 center dot 10 h-1) were switched to a feed containing glucose as the sole carbon source, growth ceased after approximately 4 h and, consequently, the cultures washed out. The mutant was, however, able to grow in chemostat cultures on mixtures of glucose and small amounts of ethanol or acetate (5% on a carbon basis). No growth was observed when such cultures were used to inoculate batch cultures on glucose. Furthermore, when the mixed-substrate cultures were switched to a feed containing glucose as the sole carbon source, wash-out occurred. It is concluded that the mitochondrial pyruvate dehydrogenase complex cannot function as the sole source of acetyl-CoA during growth of S. cerevisiae on glucose, neither in batch cultures nor in glucose-limited chemostat cultures.
Culture Media↗
Hypertension and renal disease: role of microalbuminuria.
RISKS ASSOCIATED WITH HYPERTENSION: Hypertension is a risk factor for cardiovascular and possibly renal organ damage. Microalbuminuria is a newly recognized cardiovascular and renal risk factor in diabetic and non-diabetic subjects. The prevalence of microalbuminuria is enhanced in hypertensive subjects, in particular in those with blood pressure characteristics that are associated with enhanced cardiovascular risk, such as salt-sensitivity and an abnormal diurnal blood pressure rhythm. NEED FOR FURTHER TRIALS: Although microalbuminuria is more prevalent in hypertensives and is shown to be a strong and independent risk factor, the relation between microalbuminuria and hypertensive complications is unknown. Even more intriguing is the finding of elevated levels of microalbuminuria in normotensive children with one or two parents with hypertension. This suggests that microalbuminuria is linked to the pathogenesis of hypertension. However, the role and the cause(s) of microalbuminuria are uncertain. Microalbuminuria seems to link renal and cardiovascular organ damage. Microalbuminuria might be the consequence of (renal) organ damage induced by hypertension. Alternatively, microalbuminuria might be an independent marker of some process that occurs separately from diabetes, hypertension or dyslipidemia. Endothelial dysfunction has been suggested to underlie renal and/or cardiovascular organ damage in these diseases. More knowledge should be obtained on the cause and the natural course of microalbuminuria. CONCLUSION: Microalbuminuria possibly identifies at an early stage hypertensive patients with an enhanced risk of developing the well-known renal and cardiovascular hypertensive complications. For the patients at particular risk therapeutic measures than can be developed. If microalbuminuria identifies a specific underlying pathogenetic mechanism, these measures may intervene with such a mechanism. Alternatively, if microalbuminuria identifies enhanced risk then standard antihypertensive therapy can be intensified, since such measures also lower microalbuminuria.
Albuminuria↗
Renal function during antihypertensive treatment.
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Antihypertensive Agents↗
Noninvasive measurement of intrarenal blood flow distribution: kinetic model of renal 123I-hippuran handling.
A new technique for noninvasive measurement of intrarenal blood flow distribution over cortex and medulla is proposed. The technique involves analysis of 123I-labeled hippuran renography, according to a kinetic model that describes the flow of 123I-hippuran from the heart (input) through the renal cortex and medulla to the bladder (output). The method is validated and compared with the standard microsphere injection technique in anesthetized dogs. Changes in intrarenal blood flow distribution were induced by infusion of placebo (n = 6), angiotensin I (n = 5), or atrial natriuretic factor (n = 5). Baseline percentage medullary blood flow in the left kidney was 12 +/- 1% of total renal blood flow measured with microspheres and 15 +/- 1% with renography. During infusion of the placebo, medullary blood flow decreased slightly compared with baseline, as measured with both methods, by 2 +/- 6 (microspheres) and 1 +/- 8% (renography). Infusion of angiotensin I caused a marked fall in medullary blood flow by 42 +/- 11 (microspheres) and 57 +/- 8% (renography). In contrast, infusion of atrial natriuretic factor caused a small rise in medullary blood flow as measured with both methods (9 +/- 3 and 12 +/- 11%, respectively). The absolute and percent changes in medullary blood flow measured with renography correlated with those measured with microspheres (left kidney: r = 0.67, P = 0.005; r = 0.71, P = 0.003, respectively; right kidney: r = 0.62, P = 0.01; r = 0.68, P = 0.004, respectively). We conclude that the proposed kinetic model of renal 123I-hippuran handling can be used to measure changes in intrarenal blood flow distribution and, because of its noninvasive character, may be of use in clinical studies.
Angiotensin I↗
The influence of respiration induced motion of the kidneys on the accuracy of radiotherapy treatment planning, a magnetic resonance imaging study.
An MRI study has been performed to determine the respiration induced motion of the kidneys. Under normal respiration conditions displacements of the left and right kidney varied from 2 to 24 mm and 4 to 35 mm, respectively. Under forced respiration conditions displacements were larger and ranged from 10 to 66 mm for the left kidney and 10 to 86 mm for the right kidney. The influence of kidney motion on the radiation dose was determined for patients irradiated on the total abdomen for ovarian cancer with shielding of the kidneys during part of the treatment. The kidney motion resulted in a larger fraction of the kidney volume receiving a dose between 20 and 22 Gy.
Adult↗
Renal tubular sensitivity to atrial natriuretic factor in essential hypertension.
OBJECTIVE: To study the tubular site or sites of the natriuretic action of atrial natriuretic factor and the possible differences between healthy subjects and patients with essential hypertension. DESIGN: Nine healthy volunteers and six patients with essential hypertension were studied on four test days under standard conditions, water loading and hydropenia with mannitol or saline loading. On each test day baseline, atrial natriuretic factor infusion (1 microgram/min) and recovery measurements were performed after equilibrium had been reached. The measurements included the atrial natriuretic factor (ANF) plasma levels, blood pressure, glomerular filtration rate (GFR), effective renal plasma flow, urinary osmolality and the (fractional) excretions of (free) water, sodium and potassium. METHODS: Fractional free-water excretion and free-water reabsorption (as a function of osmolar clearance) were calculated during water loading and hydropenia with mannitol or saline loading, respectively, using standard formulae. [125I]-iothalamate and [131I]-hippuran were infused continuously for the measurement of GFR and effective renal plasma flow, respectively. RESULTS: The plasma ANF concentration rose five- to eightfold during the infusion of ANF, which induced an increase in urinary sodium excretion, a small increase in GFR and a decrease in the effective renal plasma flow. Moreover, ANF induced an increase in fractional free-water excretion and a decrease in fractional free-water reabsorption. These changes did not correlate with changes in GFR. The blood pressure and potassium excretion were not affected. The effects of ANF on the plasma ANF levels, natriuresis and renal haemodynamics did not differ between the normotensive and the essential hypertensives. However, the increase in fractional free-water excretion was significantly greater in the patients with essential hypertension and correlated significantly with blood pressure (r = 0.56, P < 0.05). CONCLUSIONS: These results indicate that the infusion of ANF at a low dose induces a similar natriuretic response in normotensive subjects and in patients with essential hypertension. This natriuresis is probably the result of both a glomerular and a tubular effect of ANF. Proximal as well as distal tubular sites seem to be involved. In essential hypertension an enhanced proximal as well as an impaired distal tubular action of ANF can be hypothesized.
Absorption↗
Atrial natriuretic factor: its (patho)physiological significance in humans.
The first human studies using relatively high-doses of ANF revealed similar effects as observed in the preceding animal reports, including effects on systemic vasculature (blood pressure fall, decrease in intravascular volume), renal vasculature (rise in GFR, fall in renal blood flow), renal electrolyte excretion (rises in many electrolytes), and changes in release of a number of different hormones. Whether all these changes are the result of direct ANF effects or secondary to a (single) primary event of the hormone remains to be determined. Certainly, it has been proven that more physiological doses of ANF fail to induce short-term changes in many of these parameters leaving only a rise in hematocrit, natriuresis and an inhibition of the RAAS as important detectable ANF effects in humans. This leads us to hypothesize that ANF is a "natriuretic" hormone with physiological significance. The primary function in humans is to regulate sodium homeostasis in response to changes in intravascular volume (cardiac atrial stretch). Induction of excess renal sodium excretion and extracellular volume shift appear to be the effector mechanisms. The exact mechanism of the natriuresis in humans still needs to be resolved. It appears however, that possibly a small rise in GFR, a reduction in proximal and distal tubular sodium reabsorption, as well as an ensuing medullary washout, are of importance. The pathophysiological role of ANF in human disease is unclear. One may find elevated plasma irANF levels and/or decreased responses to exogenous ANF in some disease states. Whether these findings are secondary to the disease state rather than the cause of the disease remains to be resolved. Therapeutic applications for ANF, or drugs that intervene in its production or receptor-binding, seem to be multiple. Most important could be the antihypertensive effect, although areas such as congestive heart failure, renal failure, liver cirrhosis and the nephrotic syndrome cannot be excluded. Although the data that have been gathered to date allowed us to draw some careful conclusions as to the (patho)physiological role of ANF, the exact place of ANF in sodium homeostatic control must still be better defined. To achieve this, we will need more carefully designed low-dose ANF infusion, as well as ANF-breakdown inhibitor studies. Even more promising, however, is the potential area of studies open to us when ANF-receptor (ant)agonists become available for human use.
Animals↗
Atrial natriuretic factor influences renal diurnal rhythm in essential hypertension.
We investigated in six patients with essential hypertension the effect of a low dose atrial natriuretic factor infusion for 5 days on the diurnal rhythm of renal electrolyte excretion. Atrial natriuretic factor infusion increased the net excretion of sodium and caused a delay in its time of maximal diurnal urinary excretion. Similarly, atrial natriuretic factor caused an increase in the net excretion of chloride, calcium, and magnesium and also changed the diurnal rhythms of these electrolytes. In contrast, atrial natriuretic factor did not change the net excretion of potassium, phosphate, and uric acid, nor did atrial natriuretic factor change the diurnal rhythms of these solutes. During baseline, the time points of maximal urinary excretion of sodium and potassium overlapped, whereas atrial natriuretic factor infusion caused sodium excretion to peak 2.2 +/- 0.3 hours (p less than 0.02) after the potassium excretion peak. During baseline, the time of maximal urinary excretion of sodium did not correlate with the time of highest blood pressure, whereas it correlated negatively with mean plasma aldosterone concentration. In contrast, during atrial natriuretic factor infusion the time of maximal urinary excretion of sodium correlated positively with the time of highest blood pressure, whereas it did not correlate with mean plasma aldosterone concentration. These data suggest that atrial natriuretic factor is involved with the diurnal rhythm of the urinary excretion of sodium and that atrial natriuretic factor-induced natriuresis is mediated in part by blood pressure and plasma aldosterone.
Atrial Natriuretic Factor↗