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.

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.

Role of microalbuminuria in the assessment of cardiovascular risk in essential hypertension.

Accurate cardiovascular risk evaluation is a prerequisite for devising cost-effective therapeutic strategies in patients with essential hypertension. In fact, the knowledge of concomitant risk factors, diabetes, target organ damage, or associated clinical conditions may be useful when deciding both treatment and BP goals. Thorough evaluation of target organ damage is the key to sensitive assessment of global risk, but cost-effective allocation of economic resources should also be taken into consideration. Thanks to its low cost and widespread availability, the search for microalbuminuria is a first-line tool for identifying hypertensive patients who are at higher cardiovascular risk.

Prevention and treatment of diabetic nephropathy: the program for irbesartan mortality and morbidity evaluation.

Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, with target BP < 130/80 mmHg being recommended. Angiotensin-converting enzyme inhibitors were found to be more effective than the other traditional agents in reducing the onset of clinical proteinuria in individuals with both type 1 and type 2 diabetes and incipient nephropathy. However, small trials on patients with type 2 diabetes and overt nephropathy failed to demonstrate a specific renoprotective role for this class of drugs. The aim of the Program for Irbesartan Mortality and Morbidity Evaluation was to ascertain whether angiotensin II receptor blockers are effective in both preventing the development of clinical proteinuria and delaying the progression of nephropathy in type 2 diabetes. The Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA) Study showed that, as compared with conventional therapy, irbesartan is better at preventing the development of clinical proteinuria and at restoring normoalbuminuria for comparable BP control in patients with incipient nephropathy. The Irbesartan Diabetic Nephropathy Trial showed that irbesartan is more effective than traditional antihypertensive therapies in reducing the progression toward ESRD in patients with type 2 diabetes and overt nephropathy regardless of changes in BP. Moreover, secondary analysis of the Irbesartan Diabetic Nephropathy Trial showed that the achieved systolic pressure as well as baseline and current proteinuria significantly predict renal outcomes. In conclusion, the results of the Program for Irbesartan Mortality and Morbidity Evaluation demonstrate that irbesartan significantly prevents the development of clinical proteinuria in individuals with microalbuminuria and delays the progression of nephropathy in individuals with proteinuria. Moreover, the renoprotective effects of irbesartan go beyond its effect on BP.

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.

Serum uric acid and target organ damage in primary hypertension.

The role of serum uric acid as an independent risk factor for cardiovascular and renal morbidity is controversial. A better understanding of its relationship with preclinical organ damage may help clarify the mechanism(s) implicated in the development of early cardiovascular disease. We evaluated the association between uric acid and the presence and degree of target organ damage in 425 (265 males, 160 females) middle-aged, untreated patients with essential hypertension. Left ventricular mass index and carotid intima-media thickness were assessed by ultrasound scan. Albuminuria was measured as the albumin to creatinine ratio in 3 nonconsecutive first morning urine samples. Overall, patients with target organ damage had significantly higher levels of serum uric acid as compared with those without it (presence versus absence of left ventricular hypertrophy, P=0.04; carotid abnormalities, P<0.05; microalbuminuria, P<0.004; and at least 1 versus no organ damage, P<0.03). In women, the occurrence and severity of each target organ damage we examined increased progressively from the lower to the upper serum uric acid tertiles (P<0.01). After adjustment for body mass index, age, creatinine clearance, and high-density lipoprotein cholesterol, each standard deviation increase in serum uric acid entailed a 75% higher risk of having cardiac hypertrophy and a 2-times greater risk of having carotid abnormalities. These results support the role of serum uric acid as an independent, modifiable marker of cardiovascular damage.

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.

Cardiovascular and renal risk assessment as a guide for treatment in primary hypertension.

BP levels per se may be an unreliable indicator of risk in the individual patient. In fact, the global cardiovascular profile, including the presence and degree of target organ damage, is a better predictor of future events and, therefore, should be used to choose both treatment and BP goals. However, the prevalence of target organ damage and therefore the percentage of patients who are at risk very much depends on the diagnostic techniques used. However, as a result of the high prevalence of hypertension and its financial impact on public health systems, limiting unnecessary and extensive diagnostic tests also should be a priority. The routine search for microalbuminuria may lead to the detection of a significantly greater percentage of patients who are at high risk while contributing the optimization of the cost-effectiveness of diagnostic workup in hypertensive patients.

Mild renal dysfunction and cardiovascular risk in hypertensive patients.

Mild renal dysfunction, defined as GFR <60 to 70 ml/min and/or the presence of increased urinary albumin excretion, is associated with higher cardiovascular morbidity and mortality in primary hypertension. The aim of the present study was to investigate the relationship between renal dysfunction and target organ damage (TOD), namely left ventricular hypertrophy (LVH), retinal vascular changes, and carotid atherosclerosis, in a large cohort of unselected middle-aged hypertensive patients with normal serum creatinine. A group of 934 untreated patients with primary hypertension (543 men, 391 women; mean age 50 +/- 11 yr) was studied. Renal function was estimated by the creatinine clearance using the Cockcroft-Gault formula and by the presence of albuminuria, measured as the albumin to creatinine ratio (A/C) in first morning urine samples. LVH was determined according to electrocardiographic criteria, and retinal vascular changes were evaluated by direct ophthalmoscopy in all patients. In a subgroup of patients (n = 340; 208 men, 132 women; mean age 47 +/- 9), the presence and extent of cardiac and vascular organ damage was also assessed by ultrasound techniques. Creatinine clearance was on the average 82 +/- 20 ml/min. The overall prevalence of ECG-detected LVH and retinopathy was 12 and 49%, respectively. Creatinine clearance was inversely related to duration of disease, systolic BP, serum glucose, total cholesterol, LDL cholesterol, and early signs of TOD, namely retinal vascular changes and LVH. Patients in the bottom quintile of creatinine clearance showed higher prevalence of both ECG-determined LVH (P = 0.04) and retinal vascular changes (P = 0.02). In the subgroup of patients who underwent ultrasound evaluation of cardiovascular structures, the prevalence of mild renal dysfunction was 18%, whereas the prevalence of LVH and carotid plaque was 49 and 26%, respectively. Patients with mild renal dysfunction showed higher left ventricular mass and increased intima-media thickness (P < 0.0001), as well as higher prevalence of LVH and carotid plaque as compared with those with normal renal function. Controlling for duration of hypertension and mean BP, the risk of TOD in our cohort increased by 20% for each 10 ml/min decrease in creatinine clearance and by 30% for each 0.2 mg/mmol increase in Log A/C. In conclusion, mild renal dysfunction is associated with preclinical end-organ damage in patients with primary hypertension. These data may help to explain the observed increase in cardiovascular mortality reported in these patients. The evaluation of creatinine clearance and urinary albumin excretion could be useful for identifying patients who are at higher cardiovascular risk.

[The role of angiotensin II AT1-receptor antagonists in renal and cardiac protection in type-2 diabetes mellitus]. / Il ruolo degli antagonisti del recettore AT1 dell'angiotensina II nella nefro- e cardioprotezione nel diabete mellito tipo 2.

Blood pressure reduction and intensive antihypertensive treatment are effective in reducing both microvascular and macrovascular complications in type 2 diabetes. Blood pressure target levels < 130/85 or 130/80 mmHg are now recommended. Antagonism of the renin-angiotensin-aldosterone system seems to be an important goal in the treatment of hypertension and diabetes-related complications. The renoprotective role of angiotensin-converting enzyme (ACE)-inhibitors has been well documented in type 1 diabetes; in type 2 diabetes ACE-inhibitors have been deemed more effective than other traditional drugs in reducing the onset of overt nephropathy in microalbuminuric patients (secondary prevention) but not in reducing renal dysfunction in patients with clinical proteinuria (tertiary prevention). Recently, four large trials performed on type 2 diabetes showed that angiotensin II receptor blockers (ARBs) prevent the development of clinical proteinuria in microalbuminuric patients (IRMA and MARVAL studies) and delay the progression of nephropathy towards end-stage renal failure in patients with overt nephropathy (IDNT and RENAAL studies). Moreover, ARBs have been deemed more effective in reducing hospitalizations for heart failure compared to placebo (IDNT and RENAAL studies) and in reducing cardiovascular morbidity and mortality compared to conventional therapy (LIFE study) in type 2 diabetes. In conclusion, ARBs are effective in preventing and delaying renal damage in type 2 diabetes. Thus, the recent guidelines for the prevention and treatment of diabetic nephropathy state that ACE-inhibitors are the first-choice drugs in type 1 diabetes while ARBs are considered as the first-choice drugs in secondary prevention, the same as ACE-inhibitors, and are the unique first-choice drug in tertiary prevention of end-stage renal failure in type 2 diabetes. Finally, ACE-inhibitors and ARBs are both first-choice drugs in cardiovascular prevention in type 2 diabetes.

Mild renal dysfunction and subclinical cardiovascular damage in primary hypertension.

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, 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.

Renal and cardiovascular protection in type 2 diabetes mellitus: angiotensin II receptor blockers.

Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, and target BP less than 130/85 or 130/80 mmHg are now recommended. Inhibition of renin angiotensin aldosterone system (RAAS) plays an essential role in the treatment of hypertension and diabetes-related complications. Studies focusing on renal end-points suggest that angiotensin-converting enzyme inhibitors (ACE-I) are more effective than other traditional agents in reducing the onset of clinical proteinuria in both type 1 and type 2 diabetic patients with incipient nephropathy, mainly in normotensive ones (secondary prevention). However, several small trials in type 2 diabetic patients with overt nephropathy (tertiary prevention) failed to demonstrate a specific renoprotective role for ACE-I, at variance with type 1 diabetes. Three recent large trials address the question of whether angiotensin II receptor blockers (ARB) prevent the development of clinical proteinuria or delay the progression of nephropathy in type 2 diabetes. The IRMA study showed that irbesartan is more effective than conventional therapy in preventing the development of clinical proteinuria and in favoring the regression to normoalbuminuria for comparable BP control in patients with incipient nephropathy. The IDNT and RENAAL trials showed that ARB are more effective than traditional antihypertensive therapies in reducing progression toward end-stage renal failure (ESRF) in type 2 diabetic patients with overt nephropathy independently of changes in BP. Moreover, a reduction in hospitalizations for heart failure was demonstrated for ARB-treated patients compared with placebo. Furthermore, the LIFE study showed that losartan is more effective than conventional therapy in reducing cardiovascular morbidity and mortality in a cohort of diabetic patients with hypertension and left ventricular hypertrophy. In conclusion, ARB seem to be effective in both preventing renal damage and reducing progression toward ESRF in type 2 diabetic patients. Thus, the guidelines for the prevention and treatment of diabetic nephropathy are now changed. In type 1 diabetes ACE-I are the first-choice drug; in type 2 diabetes, ARB are considered first-choice drugs in secondary prevention as well as ACE-I and have been now elected the unique first-choice drug in tertiary prevention of ESRF. Finally, ARB should be considered as the first-choice drug in cardiovascular prevention too, as well as ACE-I.

Microalbuminuria and subclinical cerebrovascular damage in essential hypertension.

BACKGROUND: Microalbuminuria is a marker of hypertensive and atherosclerotic organ damage in essential hypertension and has powerful prognostic value for cerebral and cardiovascular morbidity and mortality. An association between carotid artery intima-media thickness (IMT) and increased urinary albumin excretion (UAE) has been reported in patients with essential hypertension, suggesting a link between microalbuminuria and atherosclerotic stroke mechanism(s). METHODS: We investigated the relationships between UAE, carotid artery changes, and asymptomatic cerebrovascular damage in two groups of untreated essential hypertensive patients, with (n=11) and without (n=11) microalbuminuria. The study groups, selected among participants in a large epidemiological trial, were carefully matched for several potential confounding variables such as sex, age, duration of hypertension, and body mass index. None had neurological abnormalities. Albuminuria was measured as albumin excretion rate (UAE) on three overnight collections; microalbuminuria was defined as between 20-200 microg/min. Carotid IMT was assessed by high resolution US scan, cerebral lacunar lesions by magnetic resonance imaging (MRI), and left ventricular mass index (LVMI) by M-B mode echocardiography. Office and 24-h ambulatory blood pressures (ABP, Takeda 2420) were also recorded. RESULTS: There were no differences between the two groups in office and ABP, lipid profile and smoking habits. Microalbuminuric patients had a higher prevalence of cerebral ischemic lacunae (82 vs 27%; P=0.03, OR=12, confidence interval - CI 1.6-91.1), and higher carotid IMT (0.94+/-0.05 vs 0.75+/-0.06 mm; P=0.03) than normoalbuminuric patients. No differences were found in LVMI and in the prevalence of Left Ventricular hypertrophy. Patients with ischemic lacunae showed a higher prevalence of microalbuminuria (75 vs 22%; P=0.03, OR=12, CI 1.0-13.5) and higher UAE (58.7+/-21.8 vs 9.4+/-3.7 mg/mmol, P=0.01) than to patients with normal MRI. CONCLUSIONS: Microalbuminuria is an early marker of preclinical brain damage in essential hypertension and may therefore be useful for identifying patients at higher risk of cerebral and cardiovascular events, for whom preventive therapeutic measures are advisable.

Pulse pressure and subclinical cardiovascular damage in primary hypertension.

BACKGROUND: High pulse pressure (PP) values have recently been implicated in the development and progression of large vessel atherosclerosis, small vessel disease, and in the occurrence of cardiovascular events. The aim of the present study is to investigate the relationship between PP and subclinical cardiovascular damage in a cohort of unselected middle-aged patients (204 male, 129 female) with untreated primary hypertension. METHODS: PP was calculated as the difference between systolic (SBP) and diastolic blood pressure (DBP). Left ventricular mass index (LVMI) was assessed by M-B mode echocardiography (LVH=LVMI>51 g/m(2.7)), and carotid intima-media thickness (IMT) by high-resolution US scan. Albuminuria was measured as the albumin to creatinine ratio (ACR) in three non-consecutive first morning urine samples. RESULTS: PP was positively correlated to gender (P<0.05), duration of disease (P<0.001), age (P<0.0001), LDL cholesterol (P=0.007), and to early signs of target organ damage (TOD), namely LVMI (P<0.0001), IMT (P<0.0001), and ACR (P=0.036). Patients in the upper quartile of PP showed higher LVMI (P<0.001), thicker carotid walls (P<0.001), as well as higher ACR (P<0.04). Multiple linear regression analysis showed that PP and ACR independently influence LVMI (F=26.476, r(2)=0.29, P<0.0001) and IMT (F=17.813, r(2)=0.26, P<0.0001). Patients with LVH, increased carotid IMT and microalbuminuria showed higher PP values as compared with those with lesser degrees of target organ involvement (F=4.97, P<0.003 inter-group comparison). Moreover, the risk of having the simultaneous occurrence of various signs of TOD increases significantly with each SD increase in PP or SBP, but is not influenced by DBP. CONCLUSIONS: PP is an independent marker of preclinical cardiovascular damage in relatively young patients with primary hypertension and, therefore, can be useful for identifying those at higher risk of cardiovascular events.

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; chi(2) 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, microg/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.