Cinzia Tomolillo

Prevalence and Clinical Correlates of Microalbuminuria in Essential Hypertension: The MAGIC Study

Abstract The prevalence of microalbuminuria and its relationship with several cardiovascular risk factors and target organ damage were evaluated in a cohort of 787 untreated patients with essential hypertension. Albuminuria was measured as the albumin-to-creatinine ratio in three nonconsecutive, first morning urine samples. The prevalence of microalbuminuria was 6.7%. Albuminuric patients were more likely to be men and to be characterized by higher blood pressure, body mass index, and uric acid levels and lower HDL cholesterol and HDL cholesterol−to−LDL cholesterol ratio. Piecewise linear regression analysis demonstrated that uric acid and diastolic blood pressure significantly influence albuminuria and together account for a large part of its variations. K-means cluster analysis performed on the entire cohort of patients confirmed that microalbuminuria is associated with a worse cardiovascular risk profile. Furthermore, microalbuminuria was associated with the presence of target organ damage (eg, electrocardiographic [ECG] abnormalities and retinal vascular changes). Age and the presence of microalbuminuria act as independent risk factors for the development of ECG abnormalities and retinal vascular changes. Cluster analysis allowed us to identify three subgroups of patients who differed in the presence or absence of microalbuminuria, retinopathy, and ECG abnormalities. We conclude that the prevalence of microalbuminuria in essential hypertension is lower than previously reported. Increased urinary albumin excretion is associated with a worse cardiovascular risk profile and is a concomitant indicator of early target organ damage.

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 ≥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.

Metabolic syndrome is associated with early signs of organ damage in nondiabetic, hypertensive patients

Objectives.  Hypertensive patients with metabolic syndrome (MS) are at greater risk for cardiovascular disease. To get a better understanding of the pathophysiology underlying this association, we evaluated the relationship between MS and subclinical organ damage in essential hypertensive patients.

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.

Microalbuminuria, Cardiovascular, and Renal Risk in Primary Hypertension

Microalbuminuria is defined as abnormal urinary excretion of albumin between 30 and 300 mg/d. It can be measured accurately by several widely available and sensitive methods. This abnormality can be found in 8 to 15% of nondiabetic patients with primary hypertension, although its prevalence varies greatly in the literature, likely due to differences in the methods used to detect it and to the criteria applied in the selection of patients. The pathogenetic mechanisms leading to the development of microalbuminuria are still not completely known. BP load and increased systemic vascular permeability, possibly due to early endothelial damage, seem to play a major role. Increased urinary albumin excretion has been associated with several unfavorable metabolic and nonmetabolic risk factors and subclinical hypertensive organ damage. In fact, a higher prevalence of concentric left ventricular hypertrophy and subclinical impairment of left ventricular performance, as well as the presence of carotid atherosclerosis, have been reported in patients with microalbuminuria. These associations might per se justify a greater incidence of cardiovascular events. Long-term longitudinal studies have recently confirmed the unfavorable prognostic significance of microalbuminuria in hypertensive patients. It has also been hypothesized that microalbuminuria might be a forerunner of overt renal damage in primary hypertension. Clinical studies, however, have shown conflicting results, and this hypothesis has to be considered tempting but speculative at present. In conclusion, microalbuminuria is a specific, integrated marker of cardiovascular risk and target organ damage in primary hypertension and one that is suitable for identifying patients at higher global risk. A wider use of this test in the diagnostic work-up of hypertensive patients is recommended.

Mild Renal Dysfunction and Subclinical Cardiovascular Damage in Primary Hypertension

Abstract—The presence of mild renal dysfunction is associated with high cardiovascular morbidity and mortality rates in patients with primary hypertension. The pathophysiological mechanisms underlying this association are currently unknown. We investigated the relation between mild renal dysfunction and subclinical cardiovascular organ damage in 358 never previously treated patients with primary hypertension. Mild renal dysfunction was defined as a creatinine clearance <60 mL/min and/or the presence of microalbuminuria. Left ventricular mass index and carotid intima-media thickness were assessed by ultrasound scan. The prevalence of mild renal dysfunction, left ventricular hypertrophy, and carotid plaque was 18%, 48%, and 28%, respectively. Mild renal dysfunction was related to the presence of several risk factors, such as older age, higher blood pressure levels and lipid status, and smoking habits. Patients with the highest left ventricular mass and carotid intima-media thickness (upper quartiles) showed a higher prevalence of mild renal dysfunction (P <0.0001). After adjusting for duration of hypertension, mean blood pressure, smoking habits, and age, we found that the risk of left ventricular hypertrophy and/or carotid atherosclerosis increased by 43% with each SD reduction in creatinine clearance, and by 89% with each SD increase in albuminuria. Mild renal dysfunction is associated with preclinical end-organ damage in patients with primary hypertension. These data may help explain the high cardiovascular mortality rates reported in patients with low glomerular filtration rate or with increased albuminuria. The evaluation of creatinine clearance and urinary albumin excretion could be useful for identifying subjects at higher cardiovascular risk.

Microalbuminuria identifies overall cardiovascular risk in essential hypertension: an artificial neural network-based approach.

Background Ultrasound (US) examination of heart and carotid arteries provides an accurate assessment of target organ damage (TOD) and may influence the stratification of the absolute cardiovascular risk profile. Microalbuminuria has recently proved to be a useful cost-effective marker of increased cardiovascular risk but is still too often neglected in clinical practice. Objective To evaluate how well artificial neural networks (ANNs) predict cardiovascular risk stratification by means of routine data and urinary albumin excretion, as compared to prediction by the clinical work-up suggested by the International Society of Hypertension (ISH), with and without ultrasound-determined TOD. Methods A group of 346 never previously treated essential hypertensives (212 men, 134 women, mean age 47 ± 9 years) was studied. Risk was stratified according to the criteria suggested by the 1999 WHO/ISH guidelines; first, by routine procedures alone, and subsequently by reassessment, using data on cardiac and vascular structures obtained by US evaluation. The ANN was trained and tested to predict the overall cardiovascular risk on the basis of routine clinical data and urinary albumin excretion (UAE). The impact of these three approaches on the determination of cardiovascular risk profile was evaluated. Results According to the first classification, 5.5% (n = 19) of patients were considered at low risk, 47.3% (n = 164) at medium, 26.7% (n = 92) at high and 20.6% (n = 71) at very high risk. A marked change in risk stratification, namely an increase in the prevalence of high- and very-high-risk patients (2.3% low, 29.8% medium, 42.8% high and 25.2% very high risk; χ2 15.201, P < 0.0001), was obtained when US examination of TOD was taken into consideration. On the basis of routine clinical data and UAE, the artificial neural network successfully predicted overall cardiovascular risk and allocated patients in different classes as accurately as the US-based evaluation. Conclusions The use of US techniques allows a more precise stratification of absolute cardiovascular risk in hypertensive patients as compared to routine clinical data. An ANN can accurately identify the patients’ risk status by using low-cost routine data and UAE. These results further emphasize the value of UAE in the stratification of cardiovascular risk.

Changes in Renal Resistive Index and Urinary Albumin Excretion in Hypertensive Patients under Long-Term Treatment with Lisinopril or Nifedipine GITS

Introduction: Increased renal vascular resistance and microalbuminuria are associated with hypertensive target organ damage and may be predictors of hypertensive nephrosclerosis. Aim: We investigated changes in renal resistive index (RI) and urinary albumin excretion (UAE) in a group of patients with primary hypertension before and during long-term antihypertensive treatment. Methods: Thirty-two patients were randomized to receive antihypertensive treatment with either a calcium channel blocker (nifedipine GITS, up to 90 mg/day, n = 16) or an ACE inhibitor (lisinopril, up to 20 mg/day, n = 16), alone or in association with a diuretic (chlortalidone, 25 mg/day). Blood pressure, renal resistive index (by US Doppler) and UAE (mean of three nonconsecutive timed urinary collections, µg/min) were evaluated at baseline and over the course of 24 months of treatment. Results: Both regimens effectively lowered blood pressure (mean blood pressure from 123 ± 1.8 at baseline to 103 ± 1.5 mm Hg at 24 months in the lisinopril group and from 122 ± 1.9 at baseline to 104 ± 0.8 at 24 months in the nifedipine group, p < 0.001 for both groups). Overall, blood pressure decrease was associated with a reduction in UAE and no change in RI throughout the study. However, despite similar blood pressure reduction, the two regimens showed different specific effects. Lisinopril was associated with a significant decrease in both UAE (33.8 ± 16.2 at baseline and 9.1 ± 2.1 at 24 months, p < 0.01) and renal RI (0.61 ± 0.02 at baseline and 0.56 ± 0.04 at 24 months, p < 0.05) while nifedipine GITS did not significantly influence UAE (35.7 ± 12.2 at baseline and 31.2 ± 12.1 at 24 months, n.s.) or RI (0.61 ± 0.01 at baseline and 0.59 ± 0.02 at 24 months, n.s.). Conclusion: Effective blood pressure control over a long period of time reduces the severity of organ damage, namely UAE while maintaining renovascular resistance in patients with essential hypertension. Different classes of antihypertensive agents might convey additional specific renal protection beyond blood pressure control. These data could be useful in devising individualized therapeutic strategies in hypertensive patients at increased renal risk.

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.

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.