Microalbuminuria in essential hypertension

Microalbuminuria (urinary albumin excretion equal to 30-300 mg/24 h) is a reliable indicator of premature cardiovascular mortality in diabetic patients and in the general population. In insulin-dependent and non-insulin-dependent diabetes mellitus microalbuminuria is a marker of initial diabetic nephropathy and predicts the evolution toward renal insufficiency. In essential hypertension the clinical and prognostic role of microalbuminuria is more controversial. While it is a recognised marker of cardiovascular complications and a reliable predictor of ischaemic heart disease, its prognostic value on the risk of progressive renal alterations is still uncertain because no prospective studies, taking microalbuminuria as a selection criterion and renal insufficiency as an end point, are available. Blood pressure control with antihypertensive drugs is accompanied by a reduction in urinary albumin excretion. The favourable effects of antihypertensive agents on microalbuminuria appear to be proportional to blood pressure reduction, but angiotensin-converting enzyme inhibitors and angiotensin-II-receptor antagonists show an additional beneficial effect on urinary albumin excretion. Whether the reduction of microalbuminuria obtained through pharmacological intervention has favourable prognostic implications remain to be demonstrated. However, screening for microalbuminuria is a relatively easy and inexpensive procedure and reveals a potentially treatable abnormality. Thus, considering that microalbuminuria identifies hypertensive subjects at higher risk than standard, urinary albumin excretion should be routinely measured in hypertensive patients and, in the presence of microalbuminuria, antihypertensive treatment should be intensified in order to obtain an optimal blood pressure control.     

The importance of microalbuminuria as a cardiovascular risk indicator: A review

The present review describes the knowledge of microalbuminuria as a cardiovascular risk indicator. Microalbuminuria is usually defined as a urinary albumin excretion rate of 30 to 300 mg in a 24 h urine collection, or as a urinary albumin excretion rate of 20 to 200 mg/min in a timed overnight urine collection, although microalbuminuria was demonstrated to be a predictor for cardiovascular events at levels below these conventional cut-off values. More than one consecutive urine collection is preferred given the high day to day variability of urinary albumin excretion. Microalbuminuria is frequently present and a known cardiovascular risk indicator in diabetic populations. Also, in hypertensive and general populations, microalbuminuria is common and has been associated with an adverse atherogenic risk profile and a higher prevalence of cardiovascular disease. Moreover, evidence strongly suggests that microalbuminuria is also an independent predictor of cardiovascular disease in these populations. However, more prospective studies are needed to elucidate fully the value of microalbuminuria as a cardiovascular risk indicator in hypertensive and general populations. Generalized endothelial dysfunction has been hypothesized to be the underlying factor for microalbuminuria on one hand and the underlying factor for increased cardiovascular risk on the other. In this respect, the loss of the glycosaminoglycan heparin sulphate might be an important pathophysiological mechanism. This hypothesis needs further clarification, especially in nondiabetic populations.     

Arterial hypertension, microalbuminuria, and risk of ischemic heart disease

Albumin excretion in urine is positively correlated with the presence of ischemic heart disease and atherosclerotic risk factors. We studied prospectively whether a slight increase of urinary albumin excretion, ie, microalbuminuria, adds to the increased risk of ischemic heart disease among hypertensive subjects. In 1983 and 1984, blood pressure, urinary albumin/creatinine concentration ratio, plasma total and HDL cholesterol levels, body mass index, and smoking status were obtained in a population-based sample of 2085 subjects, aged 30 to 60 years, who were free from ischemic heart disease, diabetes mellitus, and renal or urinary tract disease. Untreated arterial hypertension or borderline hypertension was present in 204 subjects, who were followed until 1993 by the National Hospital and Death Certificate Registers with respect to development of ischemic heart disease. During 1978 person-years, 18 (9%) of the hypertensive subjects developed ischemic heart disease. Microalbuminuria, defined as a urinary albumin/creatinine ratio above the upper decile (1.07 mg/mmol), was the strongest predictor of ischemic heart disease, with an unadjusted relative risk of 4.2 (95% CI 1.5 to 11.9, P=0.006) and a relative risk of 3.5 (95% CI 1.0 to 12.1, P=0.05) when adjusted for all other atherosclerotic risk factors, including age and gender. In conclusion, microalbuminuria confers a 4-fold increased risk of ischemic heart disease among hypertensive or borderline hypertensive subjects. Urinary albumin excretion should be measured regularly in a hypertension clinic, and a rigorous control of blood pressure and of other atherosclerotic risk factors is recommended in hypertensive patients with microalbuminuria.     

Microalbuminuria and urinary albumin excretion: French clinical practice guidelines

Urinary albumin excretion (UAE) may be assayed on a morning urinary sample or a 24 h-urine sample. Values defining microalbuminuria are: 1) 24-h urine sample: 30-300 mg/24 h; 2) morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mmol (women); 3) timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been obtained in humans. IN DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is associated with greater CV and renal risks in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NON-DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence of elevated UAE during follow-up is associated with poor outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive medium-risk subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is recommended annually in all subjects with microalbuminuria. MANAGEMENT: In patients with microalbuminuria, weight reduction, sodium restriction (<6 g per day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.     

Microalbuminuria in very old patients

In this study, we examined the prevalence and the amount of microalbuminuria in 59 very old subjects above 80 years (study group) and in age-matched subgroups of hypertensive (n=12) and non-insulin dependent diabetic (n=12) patients. In the study group, patients admitted with medical disorders other than renal, cardiovascular or malignant were included. Microalbuminuria was defined as urinary excretion of albumin in 24 h samples above 30 mg/24 h. Mean values for albumin excretion were 21.5±34.5 mg/24 h in the study group, 49.4±78.0 mg/24 h in the hypertension and 23.7±30.6 mg/24 h in the diabetic group (differences not significant). 11 out of 59 people of the study group (18.6%), and 3 out of 12 patients of the hypertension and the diabetes group (25%), respectively, exhibited an elevated albuminuria, indicating that the prevalence of pathological albumin excretion was similar between the three groups. Besides blood pressure, which was only elevated in the hypertension group according to the selection criteria, significant differences in age, serum creatinine or creatinine clearance were not found between the groups. We conclude that microalbuminuria is frequently found in very old patients with a prevalence of 18–25% and that risk factors such as hypertension or diabetes mellitus do not further enhance the high prevalence of albuminuria in the high age.     

Diabetes, microalbuminuria and hypertension

Diabetes is a chronic condition which poses a risk for three major complications. They are diabetic retinopathy, nephropathy and neuropathy. Almost one third of diabetic patients (IDDM or NIDDM) develop diabetic nephropathy in their life time. Because of increased vascular permeability in chronic conditions increased urinary albumin excretion in the range of 30-200 mg/L (microalbuminuria) gives an early signal of incipient diabetic nephropathy. The prevalence of microalbuminuria was found to be 41% in diabetic patients with duration of more than 5 years. Seventy percent of diabetic patients with microalbuminuria were hypertensive. ACE inhibitors are shown to have significant effects on microalbuminuria and hypertension. We conclude that microalbuminuria is an early feature of excessive capillary leakage and its assessment in diabetic patients with duration of more than 5 years provides a simple non-invasive method of early diagnosis of incipient diabetic nephropathy. An early intervention may retard the progression to end-stage renal disease (ESRD).     

Corticosteroid use and its association with microalbuminuria in the adult population

BACKGROUND: Corticosteroids exhibit a wide range of adverse effects, among which are a number of cardiovascular effects. Microalbuminuria shows a strong correlation with these cardiovascular effects and is an indicator for cardiovascular risk. We now investigate whether use of corticosteroids, either systemic or nonsystemic, is associated with microalbuminuria. METHODS: We used the data of 7010 subjects of an on-going population based study, focussed on the impact of microalbuminuria (PREVEND). Microalbuminuria was defined as urinary albumin excretion of 30-300 mg/24 h, measured as the mean of two 24-h urine collections. Corticosteroid use was measured in the year preceding the albumin measurement using community pharmacy data. RESULTS: After adjusting for age and sex, the odds ratio (OR) for having microalbuminuria was slightly elevated (1.21; 95% CI 1.03-1.41; N=1798) for corticosteroid users. The ORs were lower for subjects using only systemic corticosteroids (1.07; 95% CI 0.67-1.72; N=146), or only local corticosteroids (1.11; 95% CI 0.93-1.32; N=1442). However, the OR for subjects using both systemic and local corticosteroids was raised (1.99; 95% CI 1.42-2.77; N=210). CONCLUSION: Corticosteroid use, and especially use of both systemic and local corticosteroids is associated with microalbuminuria. Based on this investigation we cannot say if this is due to adverse effects of corticosteroids themselves, or effects of the underlying disease.     

Microalbuminuria: do we need a new threshold?

Microalbuminuria (30-300 mg of albumin/24 h) is a well-known independent risk factor for kidney and cardiovascular disease and of mortality in diabetic, hypertensive and in the general population. However, recent studies indicate that increased risk is observed at levels of albuminuria much lower than those currently employed to define microalbuminuria. Such low levels were shown to predict heart disease and death, independent of age, sex, renal function, diabetes, hypertension and lipids, in subjects with cardiovascular disease, hypertension and in the general population; as well as to predict progression to hypertension. Correction of obesity and metabolic derangements lowered levels of albuminuria below 30 mg/24 h to levels not associated with increased risk (5-7 mg/24 h). Despite the lack of outcome studies, there is substantial evidence to indicate that the threshold for defining microalbuminuria (that is, albuminuria associated with increased risk) should be lowered by nearly three to four-fold from the currently defined threshold. It would be advisable that clinical scores and future guidelines would consider including microalbuminuria at the lower rates as an independent risk factor, and as an indication for implementing early intervention. Unfortunately, and despite the abundance of evidence, albuminuria measurements are still underutilized in clinical practice.     

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.     

Microalbuminuria in patients with Type 2 diabetes mellitus from general practice: course and predictive value.

AIMS: To assess the course of microalbuminuria in patients with Type 2 diabetes mellitus in general practice and the predictive value of urinary albumin concentration on all-cause mortality, cardiovascular mortality and cardiovascular morbidity. METHODS: Cohort study in Type 2 diabetic patients tested for microalbuminuria in 1992, and re-tested in 1998. During follow-up all cardiovascular morbidity and mortality were recorded. RESULTS: Of the original sample of 317 patients, 163 patients were re-tested. The mean change in urinary albumin concentration was +16.2 mg/l (range -122.0 to +602 mg/l). Seventy-five per cent of the patients without microalbuminuria in 1992 still had no microalbuminuria in 1998 and 40% of those with microalbuminuria in 1992 reverted to normoalbuminuria in 1998. Cox survival analysis, stratified for age, showed that microalbuminuria at baseline resulted in a risk ratio of all-cause mortality of 1.4 (95% confidence interval 0.8-2.7), of cardiovascular mortality of 1.2 (0.5-2.8) and of new cardiovascular events (including cardiovascular mortality) of 1.4 (0.8-2.3). CONCLUSIONS: In the majority of patients the change of urinary albumin excretion was small, but the range was wide. A weak non-significant relationship between microalbuminuria and all-cause mortality and cardiovascular morbidity was observed.     

Predictors of renal and cardiovascular mortality in patients with non-insulin-dependent diabetes: A brief overview of microalbuminuria and insulin resistance

Both microalbuminuria and insulin resistance are present at some stage in the natural history of non-insulin-dependent diabetes mellitus (NIDDM). Microalbuminuria predicts both progression to endstage renal disease and an increase in cardiovascular mortality compared to diabetic patients without microalbuminuria. Conversely, microalbuminuria is not a strong predictor of either renal or cardiovascular mortality in hypertensive nondiabetic subjects. This difference in risk may relate to the presence of glycated albumin in patients with diabetes. Glycation of albumin occurs because of persistent hyperglycemia. Glycated albumin is directly toxic to both renal and vascular tissue through stimulation of reactive oxygen species by both renal and immune protective cells. Blunting the rise in microalbuminuria with either aggressive blood glucose control or angiotensin-converting enzyme (ACE) inhibition, early in the course of the disease, markedly reduces renal mortality. In contrast to microalbuminuria, which is a reflection of renal injury, insulin resistance is a genetically determined problem that directly relates to peripheral glucose utilization. In most cases, insulin resistance is phenotypically expressed as diabetes as a result of environmental factors such as obesity. Insulin resistance is associated with an increased risk for development of both hypertension and NIDDM as well as atherosclerosis. Diabetic or hypertensive subjects with insulin resistance have an increased risk of cardiovascular but not renal mortality. Sustained weight loss is the best way to reduce insulin resistance and arterial pressure. Additionally, blockers, more than other antihypertensive agents reduce insulin resistance. This class of drugs, however, has not been shown to reduce either microalbuminuria or overall cardio-renal mortality.     

Risk variables of insulin resistance syndrome in African-American and Caucasian young adults with microalbuminuria: the Bogalusa heart study

Microalbuminuria is a strong predictor of cardiovascular disease. Previous studies are inconsistent regarding the relationship between microalbuminuria and insulin resistance syndrome. Therefore, we examined this relationship in 1031 young adults (61% Caucasian, 39% African-American) aged 19 to 32 years. Individuals with either urinary albumin to creatinine ratio at or above the 90th percentile (age, race, and gender specific) or urinary albumin level at or above 30 mg/L were considered as having slightly elevated albumin excretion (microalbuminuria). The multiple risk variables of insulin resistant syndrome measured include body mass index, waist circumference, blood pressure (BP), triglycerides, high-density lipoprotein (HDL) cholesterol, glucose, insulin, insulin resistance index (calculated from a homeostasis model assessment equation), and uric acid. After controlling for age and gender, African-Americans with microalbuminuria by either measure had higher mean systolic (P < .001) and diastolic (P < .05) BP, prevalence of hypertension (P < .05), and, contrary to expectations, HDL cholesterol (P < .05) than those without this condition. On the other hand, Caucasians showed no such associations. In African-Americans, the above differences in BP levels persisted when hypertensive subjects were excluded. None of the other risk variables displayed any relation to microalbuminuria in both races. These results suggest that microalbuminuria is not necessarily an intrinsic component of the insulin resistance syndrome, at least in the young adult age. Furthermore, the observed association between hypertension and microalbuminuria among young African-Americans may reflect early evidence of renal dysfunction due to the burden of elevated BP in this group.     

Diagnostic significance of transferrinuria and albumin-specific dipstick testing in primary care patients with elevated office blood pressure

This study assesses the diagnostic accuracy of transferrinuria and an albumin-specific dipstick assay for detection of renal target organ damage (microalbuminuria) in hypertensive patients in a general practice setting. A spot urine sample of 130 nondiabetic patients with elevated office blood pressure readings (>140 and/or 90 mmHg) was investigated by measuring albumin to creatinine ratio (ACR) and transferrin to creatinine ratio (TCR) and by using an albumin-specific dipstick test (Micral). ACR was considered as comparative gold standard. TCR was elevated (>0.19 mg/mmol) in 26 urine samples (20.0% of the test samples). ACR was raised in 29 samples (22.3% of the test samples). Elevated TCR had a sensitivity of 97% and specificity of 91% for detection of microalbuminuria. Positive predicting value for microalbuminuria was 65%; negative predicting value was 99%. Correlation between ACR and TCR was strong (r=0.96). Dipstick testing for albumin was positive in 23 urine samples (17.7% of the test samples), 27 (20.8%) tests were false positive and six (4.6%) false negative. When dipstick was positive, the sensitivity of detecting microalbuminuria was 79%, and specificity 73%. In conclusion, detection of urinary transferrin in nondiabetic patients with hypertension is strongly associated with urinary albumin excretion. However, assessment of TCR does not identify additional patients with microalbuminuria compared to measurement of ACR alone. The semiquantitative Micral test offers a simple and valuable method to screen hypertensive patients for microalbuminuria in a primary care setting.     

Urinary albumin excretion. An independent predictor of ischemic heart disease.

Cross-sectional studies suggest that an increased urinary albumin excretion rate is associated with cardiovascular disease, dyslipidemia, and hypertension. The purpose of this study was to analyze prospectively whether the urinary albumin-to -creatinine (A/C) ratio can independently predict ischemic heart disease (IHD) in a population-based cohort. In 1983, urinary albumin and creatinine levels were measured, along with the conventional atherosclerotic risk factors, in 2085 consecutive participants without IHD, renal disease, urinary tract infection, or diabetes mellitus. The participants were followed up until death, emigration, or December 31, 1993. IHD was defined as a hospital discharge diagnosis or cause of death including the diagnoses ICD-8 and 410 to 414. Seventy-nine individuals developed IHD during the 21 130 person-years of follow-up. They were characterized by a preponderance of males and higher age, body mass index, blood pressure, lipoproteins, and proportion of current smokers. Microalbuminuria was defined as an A/C ratio) >90 percentile (>0.65 mg/mmol). When adjusted for other risk factors, the relative risk of IHD associated with microalbuminuria was 2.3 (95% CI, 1.3 to 3.9, P=0.002), and the 10-year disease-free survival decreased from 97% to 91% (P<0.0001) when microalbuminuria was present. An interaction between microalbuminuria and smoking was observed, and the presence of microalbuminuria more than doubled the predictive effect of the conventional atherosclerotic risk factors for development of IHD. It is concluded that microalbuminuria is not only an independent predictor of IHD but also substantially increases the risk associated with other established risk factors.     

Vascular endothelial growth factor: the link between cardiovascular risk factors and microalbuminuria?

BACKGROUND: Microalbuminuria, i.e. slightly elevated urinary albumin excretion, is associated with increased cardiovascular risk factors and cardiovascular morbidity in the general population. Microalbuminuria has been proposed to indicate increased endothelial permeability. Unknown are the mechanisms underlying this increased vascular permeability. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, increases endothelial permeability. We hypothesised that plasma VEGF levels may be associated with microalbuminuria in a large sample of the general population. METHODS: Out of a large sample of the general population, we studied 189 control subjects (urinary albumin excretion (UAE): 0-30 mg/24 h) and 194 microalbuminuric subjects (UAE: 30-300 mg/24 h), matched for age, sex and the presence of ischemia on the electrocardiogram. RESULTS: Subjects with microalbuminuria had significant higher plasma levels of VEGF (p<0.05). The correlation between plasma levels of VEGF and systolic and diastolic blood pressure, cholesterol, glucose, diabetes and body mass index were statistically significant. Using logistic regression analysis, microalbuminuria was significantly associated with VEGF (odds ratio 1.62; 95% confidence interval: 1.15-2.27; p<0.01). This association was dependent on cardiovascular risk factors. CONCLUSION: This study suggests a relation between increased plasma VEGF levels and subsequent occurrence of microalbuminuria.     

Microalbuminuria and cardiovascular risk

Microalbuminuria is a marker for generalized vascular dysfunction. Its prevalence in United States and European general population surveys ranges from 6% to 10%. Increased risk for cardiovascular morbidity and mortality begins with albumin excretion rates that are well within normal limits. Although microalbuminuria interacts with the traditional cardiovascular risk factors, it has an independent relationship to renal and cardiovascular outcomes. For example, microalbuminuria doubles the risk for a cardiovascular event in patients with type 2 diabetes mellitus even after adjusting for the usual risk factors. Elevated rates of urinary albumin excretion predict target organ damage, notably renal disease, but are also related to left ventricular dysfunction, stroke, and myocardial infarction. Screening for microalbuminuria, which is recommended by several expert committees and associations, has become a readily accessible procedure. Screening can give clinicians prognostic information concerning cardiovascular risk and assist in guiding therapy. The goal of treatment is to prevent progression of, and even to reverse, microalbuminuria. Abundant evidence demonstrates that antihypertensive therapy is an important key to the control of urinary albumin excretion, and blockade of the renin-angiotensin system (with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) is the treatment of choice. These drugs have successfully halted or delayed the progression to nephropathy and have reversed elevated rates of albumin excretion to normal values, even when blood pressure reduction has been minimal.     

Global risk stratification in primary hypertension: the role of the kidney

OBJECTIVE: Microalbuminuria and a reduction in creatinine clearance are well known, independent predictors of unfavourable cardiovascular prognosis. Our aim was to evaluate the impact of renal damage on global risk stratification in 459 non-diabetic, untreated hypertensive patients (64% men, mean age 47.3 years). METHODS: Renal damage was defined as creatinine clearance < 60 ml/min per 1.73 m2 (Cockcroft-Gault formula) or the presence of microalbuminuria (albumin to creatinine ratio). Cardiac and vascular organ damage was assessed by ultrasound scan. We evaluated the impact of renal damage, left ventricular hypertrophy and carotid atherosclerosis on risk stratification as recommended by the 2007 European Society of Hypertension-European Society of Cardiology Guidelines. RESULTS: The prevalence of renal damage, microalbuminuria and creatinine clearance < 60 ml/min per 1.73 m2 was 24, 12 and 13%, respectively. There was no correlation between albuminuria and estimated creatinine clearance, and only 0.9% of patients showed microalbuminuria and reduced creatinine clearance simultaneously. The presence of renal damage entailed a 3.3 times higher risk of having cardiovascular abnormalities. Based on routine work-up, 58% of our study patients were classified as high-very high risk. The simultaneous evaluation of albuminuria and creatinine clearance resulted in a significant change in risk stratification, since 68% of patients were classified in the high-very high risk class. The search for left ventricular hypertrophy or carotid atherosclerosis by ultrasonography did not improve risk stratification significantly as compared to the assessment of renal damage. CONCLUSIONS: Our findings support the assessment of renal abnormalities as the first step when evaluating target organ damage for cardiovascular risk assessment in hypertensive patients.     

Long-term impact of systolic blood pressure and glycemia on the development of microalbuminuria in essential hypertension

The objective was to assess the temporal impact of factors related to the development of microalbuminuria during the follow-up of young adult normoalbuminurics with high-normal blood pressure or at stage 1 of essential hypertension. Prospective follow-up was conducted on 245 normoalbuminuric hypertensive subjects (mean age 40.9 years; 134 men; blood pressure 139.7/88.6 mm Hg; body mass index 28.5 kg/m2) never treated previously with antihypertensive drugs, with yearly urinary albumin excretion measurements, until the development of microalbuminuria. After enrollment, patients were placed on usual care including nonpharmacological treatment or with an antihypertensive drug regime to achieve a blood pressure of <135/85 mm Hg. Thirty subjects (12.2%) developed microalbuminuria after a mean follow-up of 29.9 months (range 12 to 144 months), 2.5 per 100 patients per year. Baseline urinary albumin excretion (hazard ratio, 1.07; P=0.006) and systolic blood pressure during the follow-up (hazard ratio, 1.03; P=0.008) were independent factors related to the follow-up urinary albumin excretion in a Cox proportional hazard model. A significant increase in the risk of developing microalbuminuria for urinary albumin excretion at baseline >15 mg per 24-hour systolic blood pressure >139 mm Hg and a positive trend in fasting glucose were observed in the univariate analyses. However, in the multivariate analysis, only the baseline urinary albumin excretion and the trend of fasting glucose were independently related to the risk of developing microalbuminuria. In mild hypertensives, the development of microalbuminuria was linked to insufficient blood pressure control and to a progressive increment of glucose values.     

Nifedipine and enalapril equally reduce the progression of nephropathy in hypertensive type 2 diabetics.

The Japan Multicenter Investigation of Antihypertensive Treatment for Nephropathy in Diabetics (J-MIND) study was conducted to evaluate the effect of nifedipine retard or enalapril on nephropathy in hypertensive patients with type 2 diabetes. A total of 436 patients with normoalbuminuria [urinary albumin excretion rate (AER) <30 mg/day] or microalbuminuria [AER: 30-300 mg/day] were randomized to receive nifedipine retard or enalapril and were followed for 24 months. There were no differences in baseline characteristics between the two groups (the mean AER was 45 and 42 mg/day, respectively). Intent-to-treat analysis showed no significant difference in AER after 2 years, although the mean AER increased to 64 and 74 mg/day in the nifedipine retard and enalapril groups, respectively. The AER increased in patients with normoalbuminuria, whereas it did not change in those with microalbuminuria. There were no differences between the two groups with respect to progression from normoalbuminuria to microalbuminuria, progression from microalbuminuria to overt proteinuria, and regression from microalbuminuria to normoalbuminuria. The incidence of cardiovascular events was also similar in both groups. In conclusion, nifedipine retard and enalapril had a similar effect on nephropathy in hypertensive type 2 diabetic patients without overt proteinuria.     

Low muscular mass and overestimation of microalbuminuria by urinary albumin/creatinine ratio

Microalbuminuria is a mild urinary albumin elevation and is associated with cardiovascular disease. Urinary albumin/creatinine ratio is recommended for microalbuminuria assessment, because it reflects urinary albumin excretion. Muscular mass could affect albumin/creatinine ratio, because urinary creatinine reflects muscular mass. The study investigated high albumin/creatinine ratio attributed to low urinary creatinine without microalbuminuria. The Gubbio Population Study for ages 45 to 64 collected data on weight, skinfold, urinary albumin, urinary creatinine, and coronary heart disease. Weight and skinfold thickness were used to calculate fat and nonfat mass and urinary creatinine as a marker of muscular mass. Microalbuminuria was defined as urinary albumin of 20 to 199 microg/min and high albumin/creatinine ratio as a ratio of 17 to 250 microg/mg in men and of 25 to 355 microg/mg in women. Persons with macroalbuminuria (urinary albumin > or =200 microg/min) were excluded to focus analyses on microalbuminuria. Coronary heart disease was defined by ECG and questionnaire. The target cohort consisted of 1623 men and women, ages 45 to 64. Prevalence was 8.5% for high albumin/creatinine ratio (n=138), 4.3% for microalbuminuria (n=69), 5.2% for high albumin/creatinine ratio without microalbuminuria (n=85), and 1.0% for nonhigh albumin/creatinine ratio with microalbuminuria (n=16). High albumin/creatinine ratio without microalbuminuria was inversely associated with nonfat mass and urinary creatinine (P<0.04). Compared with persons with a nonhigh albumin/creatinine ratio, coronary heart disease was more prevalent in persons with a high albumin/creatinine ratio and microalbuminuria (18.9% and 7.1%; P=0.002), not in persons with a high albumin/creatinine ratio without microalbuminuria (8.2% and 7.1%; P=0.706). A high albumin/creatinine ratio in persons with low muscle mass indicates low urinary creatinine more often than microalbuminuria and cardiovascular disease.