Microalbuminuria is a predictor of chronic renal insufficiency in patients without diabetes and with hypertension: the MAGIC study.

BACKGROUND AND OBJECTIVES: Increased urinary albumin excretion is a known risk factor for cardiovascular events and clinical nephropathy in patients with diabetes. Whether microalbuminuria predicts long-term development of chronic renal insufficiency (CRI) in patients without diabetes and with primary hypertension remains to be documented. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted an 11.8-year follow-up of 917 patients who did not have diabetes and had hypertension and were enrolled in the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) cohort between 1993 and 1997. Urinary albumin-to-creatinine ratio (ACR) was assessed at baseline in untreated patients in a core laboratory. Microalbuminuria was defined as ACR > or =22 mg/g in men and ACR > or =31 mg/g in women. RESULTS: A total of 10,268 person-years of follow-up revealed that baseline microalbuminuria was associated with an increased risk for developing CRI (relative risk [RR] 7.61; 95% confidence interval [CI] 3.19 to 8.16; P < 0.0001), cardiovascular events (composite of fatal and nonfatal cardiac and cerebrovascular events; RR 2.11; 95% CI 1.08 to 4.13; P < 0.028), and cardiorenal events (composite of former end points; RR 3.21; 95% CI 1.86 to 5.53; P < 0.0001). Microalbuminuria remained significantly related to CRI (RR 12.75; 95% CI 3.62 to 44.92; P < 0.0001) and cardiorenal events (RR 2.58; 95% CI 1.32 to 5.05; P = 0.0056) even after adjustment for several baseline covariates. CONCLUSIONS: Microalbuminuria is an independent predictor of renal and cardiovascular complications in patients without diabetes and with primary hypertension.

Combined effect of albuminuria and estimated glomerular filtration rate on cardiovascular events and all-cause mortality in uncomplicated hypertensive patients.

OBJECTIVES: Decreased glomerular filtration rate (GFR) and microalbuminuria predict cardiovascular events and mortality in the general population and in high-risk patients. Their combined prognostic power in low-risk patients has never been reported. We assessed the prognostic role of GFR and albuminuria for cardiovascular disease and all-cause mortality in nondiabetic patients with primary hypertension. METHODS: We conducted an 11.2-year follow-up of 837 uncomplicated hypertensive patients enrolled in the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) cohort between 1993 and 1997. Urinary albumin-to-creatinine ratio (ACR) and estimated GFR (eGFR) were assessed in untreated patients at baseline. Renal dysfunction was defined as the inclusion in the most unfavorable sex-specific decile of eGFR or of ACR. The primary endpoints were the occurrence of fatal and nonfatal cerebrovascular and cardiac events (CVEs), composite of nonfatal cerebrovascular and cardiac events (CVD) and all-cause death (CEP), and composite of CVD and chronic renal insufficiency (CRE). RESULTS: During 9374 person-years of follow-up, the incidence rate for CVE, CRE, and all-cause mortality was 6.3, 7.8, and 3.1 /1000 person-years, respectively. Renal dysfunction was associated with increased risk for CVE [relative risk (RR) 2.13, 95% confidence interval (CI) 1.15-3.93, P = 0.011], CEP (RR 1.78, 95% CI 1.02-3.08, P = 0.027), and CRE (RR 2.47, 95% CI 1.45-4.29, P < 0.001), even after adjusting for several baseline covariates such as sex, duration and severity of blood pressure, and total cholesterol. CONCLUSION: Renal dysfunction is a risk factor for cardiorenal events and all-cause mortality, regardless of traditional confounders, in uncomplicated patients with primary hypertension.

Renal and cardiac abnormalities in primary hypertension.

OBJECTIVE: The relationship between mild reduction in renal function and cardiac structure and function have not yet been fully elucidated. We investigated cardiac and renal abnormalities in 400 untreated, nondiabetic patients (65% men, mean age 47 years) with primary hypertension and normal serum creatinine. METHODS: Renal abnormalities were defined as creatinine clearance less than 75 ml/min per 1.73 m2 (Cockcroft-Gault formula) and/or the presence of microalbuminuria (albumin-to-creatinine ratio). Left ventricular structure and function were assessed by echocardiography. RESULTS: The prevalence of microalbuminuria and reduced creatinine clearance was 13 and 31%, respectively. Patients with renal abnormalities shared greater left ventricular mass index, higher prevalence of left ventricular hypertrophy, and unfavorable geometric patterns. Microalbuminuria was also associated with inappropriate left ventricular mass and depressed midwall fractional shortening, whereas reduced creatinine clearance was associated with lower stroke volume and higher central pulse pressure/stroke volume ratio and total peripheral resistance. Stepwise regression analysis showed that both albuminuria and creatinine clearance were independently related to left ventricular mass. Logistic regression analysis of the reciprocal interaction of microalbuminuria and reduced creatinine clearance on the occurrence of subclinical cardiac damage showed that reduced creatinine clearance entailed a greater risk of left ventricular hypertrophy in patients with normal albuminuria alone, whereas the presence of microalbuminuria was associated with a greater risk of left ventricular hypertrophy independently of creatinine clearance. CONCLUSIONS: These findings provide further proof of the role of cardiorenal interaction in the development of hypertension-related cardiovascular disease, and may have clinical implications.

Vascular permeability, blood pressure, and organ damage in primary hypertension.

Sub-clinical organ damage is a strong independent predictor of cardiovascular mortality in primary hypertension, and its changes over time parallel those in risk of cardiovascular events. A better understanding of the pathogenetic mechanisms underlying the development of target organ damage may help us devise more effective therapeutic strategies. We therefore investigated the relationship between the presence of organ damage and some of its potential determinants, such as blood pressure severity and early atherosclerotic abnormalities. Thirty-seven untreated, non-diabetic hypertensive patients were enrolled. Target organ damage was assessed by albuminuria and left ventricular mass index; systemic vascular permeability was evaluated by transcapillary escape rate of albumin (TERalb); and blood pressure was measured by 24h ambulatory blood pressure monitoring. The albumin-to-creatinine ratio and left ventricular mass index were directly related to TERalb (r = 0.48, p = 0.003 and r = 0.39, p < 0.020, respectively) and 24-h systolic blood pressure values (r = 0.54, p < 0.001; r = 0.60, p < 0.001). The simultaneous occurrence of increased blood pressure load and TERalb was associated with higher left ventricular mass index values (p = 0.012) and entailed an increased risk of having at least one sign of damage (chi2 = 17.4; p < 0.001). Logistic regression analysis showed that the risk of presenting at least one sign of organ damage increased more than ten-fold when TERalb was above the median and more than five-fold with each 10 mmHg increase in 24-h systolic blood pressure. Blood pressure load and vascular permeability are potentially modifiable factors that are independently associated with the occurrence of sub-clinical signs of renal and cardiac damage in hypertensive patients.

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.

Inappropriate left ventricular mass is associated with microalbuminuria independently of left ventricular hypertrophy in primary hypertension.

OBJECTIVE: Inappropriate left ventricular mass (LVM) and microalbuminuria predict cardiovascular events in hypertension. We attempted to evaluate the relationship between inappropriate LVM and albuminuria in hypertensive patients. PATIENTS AND METHODS: Four hundred and two nondiabetic, untreated patients with primary hypertension were studied. The appropriateness of LVM to cardiac workload was calculated by the ratio of observed LVM to the predicted value using the reference equation. Albuminuria was evaluated by the urinary albumin to creatinine ratio. RESULTS: The deviation of LVM from the predicted value was positively related to albuminuria (P < 0.0001). Multiple regression analysis showed that albuminuria (0.0182), pulse pressure (P < 0.0001) and left ventricular hypertrophy (LVH) (P < 0.0001) were the only independent predictors of observed/predicted LVM. When subjects were divided into subgroups on the basis of the presence/absence of inappropriate LVM, patients with inappropriate LVM showed higher urinary albumin excretion (P < 0.0001), regardless of potential confounding factors, including LVH (analysis of covariance, P = 0.0453), and higher prevalence of microalbuminuria (P = 0.0024) compared to those without it. Analogous results were obtained by looking at the study patients on the basis of the presence of micro- or normoalbuminuria. Indeed, patients with microalbuminuria showed higher prevalence of inappropriate LVH compared to other left ventricular geometries (appropriate LVH and absence of LVH) (P < 0.0001). After adjusting for confounders, microalbuminuria entailed a three- and five-fold greater risk of having appropriate and inappropriate LVH, respectively. CONCLUSIONS: Inappropriate LVM is associated with albuminuria in hypertension. These data strengthen the role of microalbuminuria as an indicator of high cardiovascular risk.

Mild hyperuricemia and subclinical renal damage in untreated primary hypertension.

BACKGROUND: Subclinical renal damage and hyperuricemia are not uncommon in patients with primary hypertension. Whether mild hyperuricemia reflects a subclinical impairment of renal function or contributes to its development is currently debated. We investigated the relationship between serum uric-acid levels and the occurrence of early signs of kidney damage. METHODS: Four hundred eighteen patients with primary hypertension were studied. Albuminuria was measured as the albumin-to-creatinine ratio, and creatinine clearance was estimated by the formula of Cockcroft and Gault. Interlobar resistive index and renal abnormalities, ie, the renal volume-to-resistive index ratio, were evaluated by renal Doppler and ultrasound. RESULTS: Uric acid was directly related to resistive index (P = .007) in women and to albuminuria (P = .04) in men, and was inversely related to the renal volume-to-resistive index ratio in both men (P = .005) and women (P = .02). Patients with uric-acid levels above the median showed a higher prevalence of microalbuminuria (14% v 7%, P = .012) and of renal abnormalities (41% v 33%, P = .007). Moreover, when creatinine clearance was taken as a covariate, patients with increased uric-acid levels showed higher albuminuria and resistive indices, and a lower renal volume-to-resistive index ratio. Even after adjustment for several risk factors, each standard deviation increase in serum uric acid entailed a 69% higher risk of microalbuminuria, and a 39% greater risk of ultrasound detectable renal abnormalities. CONCLUSIONS: Mild hyperuricemia is associated with early signs of renal damage, ie, microalbuminuria and ultrasound-detectable abnormalities, regardless of the glomerular filtration rate in primary hypertension.

Improving cardiovascular risk stratification: the case for redefining microalbuminuria.

Large epidemiological studies have pointed out that regardless of the degree of hypertension, the cost-effectiveness of antihypertensive treatment increases in parallel with the global burden of risk. Therefore, there has been growing interest in developing sensitive and easy-to-perform ways to accurately and inexpensively identify patients at high cardiovascular risk. Numerous studies over the past years have provided evidence that microalbuminuria is a concomitant of extrarenal signs of hypertensive organ damage, as well as a strong, independent predictor of cardiovascular and cerebrovascular events. Recent clinical data indicate that the risk of cardiovascular morbidity and mortality is linearly related to the degree of urinary albumin excretion, with no identifiable threshold or plateau. Furthermore, it has been demonstrated that a reduction in albuminuria under antihypertensive treatment is paralleled by changes in cardiovascular risk. Therefore, the routine search for microalbuminuria could lead to a significant improvement in the evaluation and treatment of patients with primary hypertension.

Blood pressure load, vascular permeability and target organ damage in primary hypertension.

BACKGROUND: Target organ damage (TOD) is an often reversible subclinical condition that may precede major cardiovascular events in primary hypertensive patients. Furthermore, TOD has been shown to be a complex, multifactorial process which does not depend on blood pressure (BP) reduction alone. We therefore investigated the relationship between BP load, vascular permeability and the occurrence of TOD. PATIENTS AND METHODS: Thirty-seven never-treated, nondiabetic hypertensive patients were enrolled. Albuminuria was measured as the albumin to creatinine ratio (ACR), left ventricular mass index (LVMI) was assessed by echocardiography, systemic vascular permeability was evaluated by transcapillary escape rate of albumin (TERalb), and BP was measured by means of 24-hour ambulatory BP monitoring. RESULTS: Patients with microalbuminuria showed higher levels of body mass index (BMI) (p<0.034), 24-hour systolic BP levels (p<0.001), left ventricular mass index (LVMI) (p=0.003) and capillary permeability to albumin (p<0.005), as compared with normoalbuminurics. Increased BP load and vascular permeability were associated with higher LVMI (p=0.012) and with an increased risk of having microalbuminuria and/or left ventricular hypertrophy (Chi square=17.4; p<0.001). Logistic regression analysis showed that the risk of having at least 1 sign of TOD was 10-fold higher in patients with TERalb above the median, and almost 5-fold higher for each 10 mm Hg increase in systolic blood pressure. CONCLUSIONS: Abnormal vascular permeability and increased BP load are potentially modifiable risk factors that are independently associated with the development of subclinical cardiac and renal damage.

C-reactive protein and target organ damage in untreated patients with primary hypertension.

High sensitivity C-reactive protein (hs-CRP) has been recognized as a risk factor for cardiovascular disease. Asymptomatic organ damage is known to precede cardiovascular events in hypertension. The aim of the present study was to investigate the relationship between hs-CRP and signs of organ damage, namely left ventricular mass index (LVMI), albuminuria, and carotid atherosclerosis in a group of hypertensive patients. One hundred and eighty-two untreated patients with primary hypertension were studied. HS-CRP was measured by immunonephelometry. LVMI was assessed by echocardiography, albuminuria was measured as albumin to creatinine ratio, and carotid atherosclerosis by ultrasonography. Patient stratification according to quartiles of hs-CRP showed a significant trend toward higher age, prevalence of left ventricular hypertrophy, and carotid plaques. Moreover, there was a significant correlation among hs-CRP quartiles and left ventricular mass index, carotid cross-sectional area, carotid plaques, and albuminuria. Multiple regression analysis showed that, after adjusting for established cardiovascular risk factors (ie, age, duration of hypertension, smoking habit, body mass index (BMI), 24-hour systolic and diastolic blood pressures, glucose, creatinine, uric acid, triglycerides, total and low-density lipoprotein cholesterol), hs-CRP remained a strong correlate of target organ damage. These results support the importance of chronic microinflammation in the development of atherosclerotic disease in hypertension.

Microalbuminuria, blood pressure load, and systemic vascular permeability in primary hypertension.

BACKGROUND: Microalbuminuria, a powerful predictor of cardiovascular events, is thought to reflect widespread subclinical vascular abnormalities. To explore the pathogenesis of increased urinary albumin excretion in primary hypertension we evaluated systemic capillary permeability and ambulatory blood pressure (BP) measurement in two groups of matched untreated patients with (n = 11) and without (n = 29) microalbuminuria. METHODS: Albuminuria was measured as the mean of albumin-to-creatinine ratio (ACR) in three nonconsecutive first morning urine samples. Systemic capillary permeability was evaluated by transcapillary escape rate of albumin (TERalb) (ie, the 1-h decline rate of intravenous (125)I-albumin). Twenty-four-hour ambulatory BP, renal hemodynamics, and hormones of the renin-angiotensin-aldosterone system (RAAS) were also assessed. RESULTS: Patients with microalbuminuria showed greater body mass index (BMI) (P < .04), higher 24-h systolic and diastolic BP levels (P = .02), and higher capillary permeability to albumin (P < .02) as compared to normoalbuminurics. Renal hemodynamics and RAAS hormones were similar in the two groups. Univariate analysis showed that urinary ACR was related to ambulatory pressure components (P < .02), TERalb (r = 0.31, P < .05), smoking habits (r = 0.36, P = .02), and left ventricular mass index (LVMI) (r = 0.57, P < .001) among the whole study group. Logistic regression analysis showed that each 1% increment in TERalb or 10 mm Hg increase in systolic BP entailed an almost three times higher risk of having microalbuminuria. CONCLUSIONS: Microalbuminuria is associated with greater systemic BP load and increased vascular permeability in patients with primary hypertension.

Ambulatory arterial stiffness index and renal abnormalities in primary hypertension.

OBJECTIVE: Arterial stiffness is a predictor of cardiovascular mortality in the general population as well as in hypertension and end-stage renal disease. We investigated the relationship between a recently proposed ambulatory blood pressure monitoring-derived index of arterial stiffness and early signs of renal damage in patients with primary hypertension. DESIGN AND SETTING: A total of 168 untreated patients with sustained primary hypertension were studied. Ambulatory arterial stiffness index (AASI) was calculated based on 24-h ambulatory blood pressure readings. Albuminuria was measured as the albumin to creatinine ratio. Creatinine clearance was estimated using the Cockcroft-Gault formula, and the interlobar resistive index was evaluated by renal ultrasound and Doppler examination. RESULTS: AASI was positively related to urinary albumin excretion and resistive index, and was negatively related to estimated creatinine clearance and renal volume to the resistive index ratio. Patients with AASI above the median (i.e. > 0.51) showed a higher prevalence of microalbuminuria and a mild reduction in creatinine clearance. Moreover, patients with microalbuminuria or a mild reduction in creatinine clearance had significantly higher AASI values compared with those without, and the greater the renal involvement, the greater the AASI. After adjusting for several potentially confounding variables, we found that each standard deviation increase in AASI (i.e. 0.16) entails an almost twofold greater risk of renal involvement. CONCLUSION: Increased AASI is independently associated with early signs of renal damage in patients with sustained primary hypertension. These results strengthen the usefulness of AASI and ambulatory blood pressure monitoring in cardiovascular risk assessment.

Increased ambulatory arterial stiffness index is associated with target organ damage in primary hypertension.

Increased arterial stiffness has been shown to predict cardiovascular mortality in patients with primary hypertension. Asymptomatic organ damage is known to precede cardiovascular events. We investigated the relationship between a recently proposed index of stiffness derived from ambulatory blood pressure (BP) and target organ damage in 188 untreated patients with primary hypertension. Ambulatory arterial stiffness index was defined as 1 minus the regression slope of diastolic over systolic BP readings obtained from 24-hour recordings. Albuminuria was measured as the albumin:creatinine ratio, left ventricular mass index was assessed by echocardiography, and carotid abnormalities were evaluated by ultrasonography. The prevalence of microalbuminuria, left ventricular hypertrophy (LVH), and carotid abnormalities was 12%, 38%, and 19%, respectively. Ambulatory arterial stiffness index was positively related to age, triglycerides, office and 24-hour systolic BP, 24-hour pulse pressure, urinary albumin excretion, and carotid intima-media thickness. Patients with microalbuminuria, carotid abnormalities, or LVH showed higher ambulatory arterial stiffness index as compared with those without it. After adjusting for confounding factors, each SD increase in ambulatory arterial stiffness index entails an &2 times higher risk of microalbuminuria, carotid abnormalities, and LVH and doubles the risk of the occurrence of >or=1 sign of organ damage. Ambulatory arterial stiffness index is associated with organ damage in patients with primary hypertension. These data strengthen the role of this index as a marker of risk and help to explain the high cardiovascular mortality reported in patients with high ambulatory arterial stiffness index.

Microalbuminuria and cardiovascular risk assessment in primary hypertension: should threshold levels be revised?

BACKGROUND: Urinary albumin excretion and left ventricular mass are related to each other and to the risk of cardiovascular events in patients with primary hypertension. We aimed to identify a lower threshold for albuminuria that might improve detection of patients with left ventricular hypertrophy (LVH) and cost-effectiveness in cardiovascular risk assessment. METHODS: Albuminuria and left ventricular mass index were assessed in 448 untreated, nondiabetic patients with primary hypertension. The impact that lower albuminuria cut-off levels might have on detecting LVH was evaluated with regard to test cost and sensitivity. This was done by a diagnostic algorithm consisting of albuminuria evaluation followed by echocardiography in the presence of normoalbuminuria. RESULTS: The area under the ROC curve of albuminuria in predicting LVH was 0.73. Using a lower albumin to creatinine ratio threshold than what is recommended by the guidelines (ie, 11.5 mg/g), the sensitivity and specificity of albuminuria in identifying patients with LVH was 39% and 92%, respectively, which translated to positive and negative predictive values of 76% and 69%, respectively. When considering only patients without electrocardiographically detected LVH, routine screening for albuminuria, followed by echocardiography in the presence of albuminuria

Predicting cardiovascular risk using creatinine clearance and an artificial neural network in primary hypertension.

OBJECTIVE: A slight reduction in estimated creatinine clearance is a predictor of unfavorable outcome in patients with primary hypertension. We evaluated how well an artificial neural network (ANN) can assess cardiovascular risk profile on the basis of estimated creatinine clearance and routine, low-cost clinical data, as compared with thorough clinical work-up, which includes an accurate assessment of target organ damage. METHODS: A group of 404 untreated patients with essential hypertension (250 men, 154 women; mean age, 47 +/- 9 years) were studied. We compared two different approaches that can be used to allocate patients into different risk classes according to the European Society of Hypertension-European Society of Cardiology guidelines: thorough clinical work-up, including cardiac and vascular ultrasound scan and microalbuminuria; and prediction by an ANN on the basis of estimated creatinine clearance and routine clinical data. RESULTS: Thorough evaluation, as recommended by the guidelines, showed that 6% (n = 24) of our patients were at low risk, 20% (n = 81) were at medium risk, 45% (n = 182) were at high risk, and 29% (n = 117) were at very high risk. The ANN approach yielded almost superimposable results (sensitivity, 94%; positive predictive value, 96%; r = 0.95). CONCLUSIONS: An ANN can accurately identify the patient's risk status using low-cost, clinical data and estimated creatinine clearance. These results emphasize the value of even a mild reduction in creatinine clearance for the stratification of cardiovascular risk in primary hypertension.

Evaluation of subclinical organ damage for risk assessment and treatment in the hypertensive patient: role of microalbuminuria.

Microalbuminuria, i.e., abnormal urinary excretion of albumin, which is detectable by low cost and widely available tests, is a first-line tool for identifying hypertensive patients who are at higher cardiovascular (CV) risk. Numerous studies have provided evidence that microalbuminuria is a concomitant of cardiac and vascular damage as well as a strong, independent predictor of CV events. An important, emerging issue is that the risk for CV morbidity and mortality is linearly related to urinary albumin excretion and persists well below the currently used cutoff for defining microalbuminuria. Furthermore, late-breaking evidence suggests that a reduction of albuminuria under antihypertensive treatment is paralleled by changes in CV risk. The routine search for target organ damage by means of microalbuminuria could lead to a significant improvement in the evaluation and treatment of patients with primary hypertension.

Metabolic syndrome and cardiovascular risk in primary hypertension.

The metabolic syndrome can be found in approximately one third of patients who do not have diabetes but have primary hypertension. Its presence has been associated with a wide range of traditional and nontraditional cardiovascular risk factors and early signs of cardiovascular and renal damage. Moreover, it was emphasized recently that the metabolic syndrome predicts an increased probability of sustaining a cardiovascular event or dying. In the clinical setting of insulin resistance, attention should be paid to the metabolic side effects of antihypertensive drugs; therefore, preference should be given to renin-angiotensin system inhibitors and calcium channel blockers rather than to beta blockers and diuretics.

Mild renal dysfunction and renal vascular resistance in primary hypertension.

BACKGROUND: Mild renal dysfunction (MRD) is an often overlooked but relatively common condition in patients with primary hypertension (PH), and is associated with high cardiovascular morbidity and mortality. Whether MRD is also associated with abnormalities in renal vascular resistance is currently unknown. METHODS: Two hundred ninety-one untreated patients with PH were studied. The MRD was defined as a creatinine clearance >or=60 mL/min but <90 mL/min (Cockcroft-Gault formula) or the presence of microalbuminuria. Albuminuria was measured as the albumin-to-creatinine ratio in first morning urine samples. Renal resistive index (RI) was evaluated by ultrasound Doppler of the interlobar arteries. RESULTS: The prevalence of MRD in our cohort was 63%. Patients with MRD were older, had higher mean blood pressure (BP), pulse pressure, and total cholesterol, longer history of hypertension, and were more likely to be men. Renal RI was positively related to female gender, age, systolic BP, pulse pressure, total cholesterol, albuminuria, and to carotid wall thickness and cross-sectional area, whereas it was inversely related to diastolic BP and creatinine clearance. Patients with the highest renal resistance (upper quartile, >or=0.63) showed a greater prevalence of renal dysfunction (P=.0005). After adjusting for age, pulse pressure, and LDL-cholesterol, we found that the risk of MRD increased twofold (P=.04) when renal RI was >or=0.63. CONCLUSIONS: A reduction in creatinine clearance and the presence of microalbuminuria are associated with increased renal vascular impedence, as well as with signs of extrarenal arterial stiffness.

Impact of target organ damage assessment in the evaluation of global risk in patients with essential hypertension.

Accurate assessment of cardiovascular risk is a key step toward optimizing the treatment of hypertensive patients. We analyzed the impact and cost-effectiveness of routine, thorough assessment of target organ damage (TOD) in evaluating risk profile in hypertension. A total of 380 never-treated patients with essential hypertension underwent routine work-up plus evaluation of albuminuria and ultrasonography of cardiac and vascular structures. The impact of these tests on risk stratification, as indicated by European Society of Hypertension-European Society of Cardiology guidelines, was assessed in light of their cost and sensitivity. The combined use of all of these tests greatly improved the detection of TOD, therefore leading to the identification of a higher percentage of patients who were at high/very high risk, as compared with those who were detected by routine clinical work-up (73% instead of 42%; P < 0.0001). Different signs of TOD only partly cluster within the same subgroup of patients; thus, all three tests should be performed to maximize the sensitivity of the evaluation process. The diagnostic algorithm yielding the lowest cost per detected case of TOD is the search for microalbuminuria, followed by echocardiography and then carotid ultrasonography. Adopting lower cut-off values to define microalbuminuria allows us to optimize further the cost-effectiveness of diagnostic algorithms. In conclusion, because of its low cost and widespread availability, measuring albuminuria is an attractive and cost-effective screening test that is especially suitable as the first step in the large-scale diagnostic work-up of hypertensive patients.

Optimizing global risk evaluation in primary hypertension: the role of microalbuminuria and cardiovascular ultrasonography.

OBJECTIVE: To assess the impact and cost-effectiveness of microalbuminuria and cardiovascular ultrasonography in evaluating the risk profile in primary hypertension. METHODS: Four hundred and five untreated patients with primary hypertension underwent a routine, traditional work-up plus evaluation of albuminuria and ultrasound (US) assessment of cardiac and vascular structures. Albuminuria was measured as the albumin to creatinine ratio in three non-consecutive first-morning urine samples. Left ventricular mass index was assessed by MB-mode echocardiography and carotid intima-media thickness by high-resolution US scan. The impact of these tests on patient risk classes, as indicated by European Society of Hypertension-European Society of Cardiology (ESH-ESC) guidelines, was assessed with respect to their cost and sensitivity. RESULTS: The prevalence of microalbuminuria, left ventricular hypertrophy and carotid intima-media thickening or carotid plaque was 13, 49 and 32%, respectively. The combined use of albuminuria, cardiac and vascular ultrasonography led to the detection of a significantly higher percentage of patients at high/very high risk. The three tests differ in sensitivity (albuminuria, 20%; echocardiography, 65%; and carotid ultrasound, 41%). The signs of target organ damage (TOD) only partly cluster within the same subgroup of patients and, thus, all three tests should be performed in order to maximize the sensitivity of the evaluation process. The diagnostic algorithm yielding the lowest cost per detected case of TOD is the search for microalbuminuria followed by cardiac and carotid ultrasound assessment. CONCLUSIONS: Ultrasonographic detection of TOD is a sensitive tool in the identification of high-risk patients, but should be preceded by a routine search for microalbuminuria in order to optimize the cost-effectiveness of the diagnostic work-up.