Volatile Anesthetics versus Propofol for Cardiac Surgery with Cardiopulmonary Bypass: Meta-analysis of Randomized Trials.

BACKGROUND: The aim of this systematic review and meta-analysis was to assess the effect of anesthesia maintenance with volatile agents compared with propofol on both short- and long-term mortality (primary outcomes) and major clinical events in adults undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Randomized clinical trials on the effects of current volatile anesthetics versus propofol in adults undergoing cardiac surgery with cardiopulmonary bypass were searched (1965 to September 30, 2019) in PubMed, the Cochrane Library, and article reference lists. A random effect model on standardized mean difference for continuous outcomes and odds ratio for dichotomous outcomes were used to meta-analyze data. RESULTS: In total, 37 full-text articles (42 studies, 8,197 participants) were included. The class of volatile anesthetics compared with propofol was associated with lower 1-yr mortality (5.5 vs. 6.8%; odds ratio, 0.76 [95% CI, 0.60 to 0.96]; P = 0.023), myocardial infarction (odds ratio, 0.60 [95% CI, 0.39 to 0.92]; P = 0.023), cardiac troponin release (standardized mean difference, -0.39 [95% CI, -0.59 to -0.18], P = 0.0002), need for inotropic medications (odds ratio, 0.40 [95% CI, 0.24 to 0.67]; P = 0.0004), extubation time (standardized mean difference, -0.35 [95% CI, -0.68 to -0.02]; P = 0.038), and with higher cardiac index/output (standardized mean difference, 0.70 [95% CI, 0.37 to 1.04]; P < 0.0001). The class of volatile anesthetics was not associated with changes in short-term mortality (1.63 vs. 1.65%; odds ratio, 1.04 [95% CI, 0.73 to 1.49]; P = 0.820) and acute kidney injury (odds ratio, 1.25 [95% CI, 0.77 to 2.03]; P = 0.358). CONCLUSIONS: In adults undergoing cardiac surgery with cardiopulmonary bypass, the class of volatile anesthetics was superior to propofol with regard to long-term mortality, as well as to many secondary outcomes indicating myocardial protection.

Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials.

Background: The main aim of this systematic review was to assess whether remote ischaemic preconditioning (RIPC) protects kidneys and the heart in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate a possible role of anaesthetic agents. Methods: Randomized clinical trials (RCTs) on the effects of RIPC through limb ischaemia in adult patients undergoing cardiac surgery with CPB were searched (1965-October 2016) in PubMed, Cochrane Library and article reference lists. A random effects model on standardized mean difference (SMD) for continuous outcomes and the Peto odds ratio (OR) for dichotomous outcomes were used to meta-analyse data. Subgroup analyses to evaluate the effects of different anaesthetic regimens were pre-planned. Results: Thirty-three RCTs (5999 participants) were included. In the whole group, RIPC did not significantly reduce the incidence of acute kidney injury (AKI), acute myocardial infarction, atrial fibrillation, mortality or length of intensive care unit (ICU) and hospital stays. On the contrary, RIPC significantly reduced the area under the curve for myocardial injury biomarkers (MIBs) {SMD -0.37 [95% confidence interval (CI) -0.53 to - 0.21]} and the composite endpoint incidence [OR 0.85 (95% CI 0.74-0.97)]. In the volatile anaesthetic group, RIPC significantly reduced AKI incidence [OR 0.57 (95% CI 0.41-0.79)] and marginally reduced ICU stay. Conversely, except for MIBs, RIPC had fewer non-significant effects under propofol with or without volatile anaesthetics. Conclusions: RIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB. In the subgroup on volatile anaesthetics only, RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury.

The role of kidney dysfunction in COVID-19 and the influence of age.

COVID-19 is strongly influenced by age and comorbidities. Acute kidney injury (AKI) is a frequent finding in COVID-19 patients and seems to be associated to mortality and severity. On the other hand, the role of kidney dysfunction in COVID-19 is still debated. We performed a retrospective study in a cohort of 174 hospitalized COVID-19 patients in Italy from March 3rd to May 21st 2020, to investigate the role of kidney dysfunction on COVID-19 severity and mortality. Moreover, we examined in depth the relationship between kidney function, age, and progression of COVID-19, also using different equations to estimate the glomerular filtration rate (GFR). We performed logistic regressions, while a predictive analysis was made through a machine learning approach. AKI and death occurred respectively in 10.2% and 19.5%, in our population. The major risk factors for mortality in our cohort were age [adjusted HR, 6.2; 95% confidence interval (CI) 1.8-21.4] and AKI [3.36 (1.44-7.87)], while, in these relationships, GFR at baseline mitigated the role of age. The occurrence of AKI was influenced by baseline kidney function, D-dimer, procalcitonin and hypertension. Our predictive analysis for AKI and mortality reached an accuracy of ≥ 94% and ≥ 91%, respectively. Our study scales down the role of kidney function impairment on hospital admission , especially in elderly patients. BIS-1 formula demonstrated a worse performance to predict the outcomes in COVID-19 patients when compared with MDRD and CKD-EPI.

CKD awareness and blood pressure control in the primary care hypertensive population.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor renal and cardiovascular outcomes, and early identification largely depends on general practitioners' (GPs') awareness of it. To date, no study has evaluated CKD prevalence in patients with hypertension in primary care. STUDY DESIGN: Cross-sectional evaluation of the Italian GPs' database. SETTING & PARTICIPANTS: 39,525 patients with hypertension representative of the Italian hypertensive population followed up by GPs in 2005. FACTOR: Estimated glomerular filtration rate (eGFR); eGFR <60 mL/min/1.73 m² was defined as CKD. OUTCOMES: GPs' awareness of CKD assessed using International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for CKD, and blood pressure (BP) control. MEASUREMENTS: Data concerning serum creatinine levels, BPs, and antihypertensive medications were obtained for each patient from the GPs' database; eGFR was calculated according to the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. RESULTS: CKD prevalence was 23%, but kidney disease was diagnosed by GPs in only 3.9% of patients. BP control was inadequate in patients with CKD and those with eGFR >60 mL/min/1.73 m², with only 44% of patients reaching a BP target <140/90 mm Hg and 11% achieving <130/80 mm Hg. Patients with eGFR <60 mL/min/1.73 m² whose GPs were aware of CKD were more likely to reach recommended BP target values (OR, 1.35; 95% CI, 1.15-1.59; P < 0.001). LIMITATIONS: The prevalence of decreased eGFR may be overestimated because of the lack of creatinine calibration. Proteinuria data were not available. CONCLUSIONS: Awareness of CKD by GPs is critical for achieving the recommended guideline BP targets. However, awareness of CKD by GPs is still far too low, highlighting the need to systematically adopt eGFR for more accurate identification of CKD in high-risk populations.

Renal dysfunction in cardiovascular diseases and its consequences.

It is well known that the heart and kidney and their synergy is essential for hemodynamic homeostasis. Since the early XIX century it has been recognized that cardiovascular and renal diseases frequently coexist. In the nephrological field, while it is well accepted that renal diseases favor the occurrence of cardiovascular diseases, it is not always realized that cardiovascular diseases induce or aggravate renal dysfunctions, in this way further deteriorating cardiac function and creating a vicious circle. In the same clinical field, the role of venous congestion in the pathogenesis of renal dysfunction is at times overlooked. This review carefully quantifies the prevalence of chronic and acute kidney abnormalities in cardiovascular diseases, mainly heart failure, regardless of ejection fraction, and the consequences of renal abnormalities on both organs, making cardiovascular diseases a major risk factor for kidney diseases. In addition, with regard to pathophysiological aspects, we attempt to substantiate the major role of fluid overload and venous congestion, including renal venous hypertension, in the pathogenesis of acute and chronic renal dysfunction occurring in heart failure. Furthermore, we describe therapeutic principles to counteract the major pathophysiological abnormalities in heart failure complicated by renal dysfunction. Finally, we underline that the mild transient worsening of renal function after decongestive therapy is not usually associated with adverse prognosis. Accordingly, the coexistence of cardiovascular and renal diseases inevitably means mediating between preserving renal function and improving cardiac activity to reach a better outcome.

Androgen-mediated apoptosis of kidney tubule cells: role of c-Jun amino terminal kinase.

The incidence and the rate of progression of chronic kidney diseases (CKD) are for most diseases greater in men than in age-matched women. We have previously shown that testosterone (T) promotes the apoptosis of proximal tubule kidney cells. To better understand the downstream signaling process associated with T-induced apoptosis, we examined the involvement of c-Jun amino terminal kinase (JNK) in a human proximal tubule cell line (HK-2) exposed to T: JNK and its downstream effector c-Jun were rapidly phosphorylated. By blocking androgen receptor, JNK phosphorylation was reduced and 17beta-Estradiol treatment had no effect on it. Similarly, pre-treatment with the JNK inhibitor SP600125 prevented the T-induced apoptosis, the phosphorylation of c-Jun and the upregulation of the Fas/FADD pathway. These data show that the JNK/c-Jun pathway is directly regulated by androgens in vitro and highlight a potential mechanism explaining the reported gender differences in the progression of renal diseases.

Independent association of ECG abnormalities with microalbuminuria and renal damage in hypertensive patients without overt cardiovascular disease: data from Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease study.

OBJECTIVES: Renal abnormalities are strongly associated with cardiac damage in essential hypertension. Detection of preclinical cardiac and renal abnormalities is a key clinical step in hypertension management. This study investigated the relationship between ECG abnormalities and microalbuminuria (MAU) in hypertensive patients without overt cardiovascular disease. This relationship, in fact, has never been extensively studied. METHODS: The study population was that of Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease, a large observational study including 4121 hypertensive patients in Italy. Patients with overt cardiovascular diseases were excluded from the present analysis. ECGs were centrally read and urinary albumin/creatinine ratio was carefully assessed. Chronic kidney disease was defined by the presence of albuminuria or by a reduction of glomerular filtration rate. RESULTS: The presence of ECG abnormalities was significantly and directly associated with chronic kidney disease [odds ratio (OR) 1.66, 95% confidence interval (CI) 1.32-2.07, P<0.001], particularly with MAU (OR 1.81, 95% CI 1.39-2.36, P<0.001). Main selected ECG abnormalities were also significantly associated with MAU [rhythm abnormalities (OR 2.94, 95% CI 1.77-4.88, P<0.001), intraventricular conduction defects (OR 1.95, 95% CI 1.32- 2.87, P<0.01), ventricular repolarization alterations (OR 1.84, 95% CI 1.26-2.70, P<0.01) and left-axis deviation (OR 1.87, 95% CI 1.26-2.79, P<0.01)]. After adjustment for confounders, an abnormal ECG and all the main ECG abnormalities remained significantly associated with MAU. CONCLUSION: This is the first large and systematic analysis of the relationship between detailed ECG abnormalities and MAU/chronic kidney disease in hypertensive patients without overt cardiovascular diseases. We report a significant and independent relationship between the presence of ECG abnormalities and renal damage in a preclinical stage of hypertension. Identification of ECG abnormalities in hypertension should prompt physicians to careful detection for renal damage, also in order to achieve an accurate risk stratification.

Chronic kidney disease and cardiovascular risk in hypertensive type 2 diabetics: a primary care perspective.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor renal and cardiovascular (CV) outcome, and early identification largely depends on the general practitioners' (GPs) awareness of it. Only a few studies have evaluated the prevalence of CKD in type 2 diabetes in primary care, and no studies are available on hypertensive diabetics. Thus, the aim of this study was to assess the prevalence of CKD and its association with CV morbidity in such a population. METHODS: On the basis of an Italian national project involving GPs and nephrologists, we retrieved demographic, laboratory and clinical data regarding 7582 hypertensive type 2 diabetics (3564 men; age 25-89 years) who were selected using the diagnostic code Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) for diabetes and hypertension. Blood pressure (BP) values, serum creatinine, ECG-diagnosed left ventricular hypertrophy (LVH) and the occurrence of previous major CV events were obtained for each patient from the GPs' Health Search Database. Estimated glomerular filtration rate (GFR) was calculated according to the four-variable MDRD equation. CKD was defined as an estimated GFR < 60 mL/min/ 1.73 m2. RESULTS: CKD prevalence was 26%, although renal disease was diagnosed by GPs in only 5.4% of cases. The prevalence of both LVH and major CV events was 8%. Adequate BP control was only achieved in 10.4% of patients. Patients whose GFR was <60 mL/min/1.73 m2 were older, prevalently female, had increased pulse pressure and higher prevalence of dyslipidaemia. Moreover, the prevalence of both LVH and major CV events was higher in patients with CKD as compared to patients with normal GFR. Multivariate logistic regression analysis showed that patients with CKD had a higher risk of LVH and/or CV events adjusted for eight covariates, and this risk increased by 23% with each 21 mL/min/1.73 m2 decrease in GFR. CONCLUSIONS: This study shows that CKD is highly prevalent in hypertensive type 2 diabetic patients, where it is a strong predictor of CV adverse outcome. However, awareness of CKD by GPs is low. Equations for calculating estimated GFR should be included in the GPs' database in order to detect the presence of CKD and to improve CV outcome of such a high-risk population.

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.

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.

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.

Emerging therapeutic strategies in diabetic nephropathy.

Diabetic nephropathy is one of the main causes of end-stage renal disease (ESRD) and is associated with elevated cardiovascular morbidity and mortality. Current renoprotective treatment for diabetic nephropathy includes strict glycemic and optimal blood pressure control, proteinuria/albuminuria reduction and the use of renin-angiotensin-aldosterone system (RAAS) blocking agents. However, the renoprotection provided by these treatments is only partial, and many patients still have progressive disease, thus suggesting that a more effective approach is urgently needed. This review examines emerging strategies for the treatment of diabetic nephropathy, including aggressive RAAS blockade, statins, pentoxifylline, glitazones, ruboxistaurin, as well as sulodexide. Pilot studies that used surrogate end points, mainly albuminuria, will be discussed. New insights suggest that treating microalbuminuric diabetic patients with statins, pentoxifylline, glitazones and sulodexide could be a new approach for reducing the incidence of clinical proteinuria. In diabetic patients with overt nephropathy, the administration of statins, pentoxifylline, sulodexide or aggressive RAAS inhibition, including RAAS dual blockade (i.e., angiotensin-converting enzyme [ACE] inhibitors plus angiotensin receptor blockers or aldosterone antagonists plus ACE inhibitors or angiotensin receptor blockers), seems to be a promising way to preserve renal function and to prevent progression to ESRD. Results of ongoing, long-term trials on major renal and cardiovascular clinical outcomes, as well as on mortality are needed to establish whether the current standard of care of diabetic nephropathy might be improved with these new strategies.

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.

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.

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, 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.

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