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Aims: Microalbuminuria (MAU) is a marker for endothelial dysfunction and a predictor of increased cardiovascular risk. Physical activity improves endothelial function. This analysis aims to explore the impact of regular physical exercise on the prevalence and the degree of MAU in hypertensive individuals at high cardiovascular risk., Methods and Results: The International Survey Evaluating microAlbuminuria Routinely by Cardiologists in patients with Hypertension (I-SEARCH) studied the prevalence of MAU in 20,786 hypertensive patients at high cardiovascular risk. Herein, we investigated the relationship between self-reported physical activity and MAU in relation to the number of cardiovascular risk factors, medication and co-morbidities. A total of 7123 patients (34.3%) performed regular physical exercise (moderate or strenuous, at least 4 hours per week). The prevalence of MAU was significantly lower in active than in inactive patients (54% vs 61%; P < 0.0001). This association was observed in all classes of blood pressure and heart rate and was similar in patients with and without diabetes mellitus. Urinary albumin excretion (UAE) was lower in active than in inactive patients (UAE 80 mg/l: 11.6% vs 13.5%, P < 0.0001; UAE 150 mg/l: 7.5% vs 10%; P < 0.0001). In a multivariate analysis adjusted for age, gender, blood pressure, heart rate, renal function, medication and comorbidities, regular physical activity was associated with a 25% lower risk for MAU (odds ratio (OR) 0.75; 95% confidence interval (CI), 0.67-0.84; P < 0.0001). Risk reduction for MAU was more pronounced in strenuously active (OR 0.66; 95%CI, 0.47-0.95; P < 0.05) than in moderately active patients (OR 0.76; 95%CI, 0.68-0.85; P < 0.0001)., Conclusion: In hypertensive patients at high cardiovascular risk, physical activity is an independent predictor for a decreased risk of microalbuminuria.

Background: Microalbuminuria (MAU) is a marker for endothelial dysfunction and a predictor of cardiovascular events. Cardiovascular risk and mortality are mainly influenced by associated morbidities and risk factors., Methods and Results: The present analysis aimed to investigate the relationship between the number of cardiovascular comorbidities and both the prevalence of MAU and the extent of albuminuria (measured as urinary albumin excretion, UAE) in 21,867 high-risk hypertensive patients included in the I-SEARCH study. A total of 6,945 patients (32 %) suffered from at least one comorbidity, out of which 5,437 patients (25 %) had one cardiovascular comorbidity, 1,163 (5 %) patients had two, and 345 (2 %) had ≥3. The prevalence of MAU increased from 54 % in patients without cardiovascular comorbidity to 74 % in the presence of ≥3 comorbidities (p < 0.01). In a multivariate analysis, the presence of ≥3 cardiovascular comorbidities nearly doubled the risk for MAU (HR 1.79, CI 1.07-2.68, p = 0.025). Compared to other comorbidities, patients with left ventricular hypertrophy had the highest prevalence of MAU (68 %, p < 0.01). The extent of UAE was related to the number of concomitant disease and increased significantly in patients with ≥3 comorbidities compared to patients with no comorbidity (UAE of 80 mg/L: 12-22 %, p < 0.01; UAE of 150 mg/L: 8-19 %, p < 0.01)., Conclusions: In hypertensive patients at high cardiovascular risk, both the prevalence of MAU and the extent of albuminuria increase with the number of comorbidities.

Background: Microalbuminuria (MAU) is a marker of endothelial dysfunction and a predictor of cardiovascular events. The effects of cigarette smoking on the prevalence of MAU in a high-risk population with arterial hypertension are unclear., Methods: The International Survey Evaluating Microalbuminuria Routinely by Cardiologists in patients with Hypertension (I-SEARCH) documented the clinical profile of 20,364 patients with arterial hypertension and cardiovascular risk factors. In this population, 13,690 patients had no history of smoking, 4,057 patients were former smokers and 2,617 patients were current smokers., Results: The prevalence of MAU was associated with the smoking status. Consumption of 1-20 cigarettes per day leads to an increase of 6.8% in the prevalence of MAU compared to non-smokers (P < 0.001). Smoking of >20 cigarettes per day was associated with a 12.5% higher prevalence of MAU compared to non-smokers, while former smokers had a 4.7% higher prevalence of MAU. Multivariable analysis revealed that smoking was independently associated with MAU [odds ratio (OR) smoking vs. non-smoking 1.16; 95% confidence interval (CI) 1.01-1.33; P < 0.05]. Particularly, a consumption of >20 cigarettes per day was associated with high odds for MAU (OR 1.33; CI 1.01-1.75; P < 0.05). Interestingly, independently of blood pressure, the use of an angiotensin receptor blocker and an ACE was associated with significantly reduced odds ratio for MAU in the smoking group, while there was no significant association in the non-smoking group., Conclusion: The prevalence of MAU in hypertensive patients is higher in smokers than in non-smokers with a strong dose dependency.

Question Under Study: The aim of this study was to determine the prevalence of microalbuminuria (MAU) in hypertensive patients attending an office or hospital based cardiologist or internist. An additional aim was to describe associations between MAU and cardiovascular risk factors as well as to investigate the role of pharmacotherapy., Methods: International, observational, cross-sectional study of 22282 patients with 5605 attendees in Germany and Switzerland at 444 cardiology centers. Inclusion criteria were male and female outpatients, aged > or =18 years with currently treated or newly diagnosed hypertension (> or =140/90 mm Hg at rest on the day of the study visit) and no reasons for false positive dip stick tests. The main outcome measures were the prevalence of MAU, co-morbid cardiovascular risk factors or disease and their association with the presence of MAU, and the role of pharmacotherapy in modulating prevalence of MAU., Results: Prevalence of MAU in Germany and Switzerland (53.1%) was high, but lower when compared to the prevalence in "other countries" (OC, 60.2%). Routine MAU measurement was performed in 52.9% of the practices only (32.9% OC), although physicians regarded MAU to be important for risk assessment and therapeutic decisions. MAU is highly correlated with a wide variety of cardiovascular risk factors and co-morbid cardiovascular conditions including high waist circumference (55.1% [95%CI 56.0; 59.7]), diabetes (59.1% [56.8; 61.3]), atrial fibrillation (62.3% [57.4; 66.9]) and peripheral arterial disease (67.1% [61.6; 72.2]). Angiotensin receptor blockers (ARBs) appeared to be associated with the lowest risk of MAU (52.1%). Calcium channel blockers (CCBs) were used more frequent in patients with MAU (28.7%) than without (23.4%)., Conclusions: Patients with MAU are common in clinical cardiology and its presence is associated with a wide variety of cardiovascular risk factors and co-morbid cardiovascular conditions. A more aggressive multi-factorial treatment might help to reduce this risk constellation.

Aims: To investigate the relationship between microalbuminuria (MAU) and atrial fibrillation (AF) and to further evaluate whether the heart rate dependency of MAU in patients without AF is maintained in patients with a history of AF., Methods and Results: The International Survey Evaluating Microalbuminuria Routinely by Cardiologists in patients with Hypertension (I-SEARCH) included 18,900 patients without and 1705 patients with a history of AF suffering from hypertension and other risk factors for cardiovascular disease in 26 countries worldwide from September 2005 to March 2006. Heart rate, blood pressure, urinary albumin excretion, and an estimated glomerular filtration rate were determined among other parameters. The prevalence of MAU was higher at higher heart rate in both patients with and without a history of AF. Prevalence of MAU was about 10% higher in patients with a history of AF (P < 0.001). Male gender, the presence of diabetes mellitus, a higher heart rate, and a higher diastolic blood pressure were independently associated with increased odds for MAU in patients without and with a history of AF., Conclusion: The prevalence of MAU in hypertensive patients with cardiovascular risk factors is related to heart rate and significantly higher in patients with a history of AF.

Background: Overweight and obesity are frequently associated with preventable death and have emerged as a major challenge to public health. There is an ongoing debate on the role of abdominal obesity and its value in predicting cardiovascular and renal outcomes. The present analysis evaluates the prevalence of microalbuminuria (MAU) and conventional cardiovascular risk factors in relation to measures of general and abdominal obesity., Methods: In this multinational, observational study, 20828 hypertensive out-patients from 26 countries including Europe, North and Latin America, Middle East, and Asia were analyzed. Urinary dipstick screening for MAU was performed as well as data on patient demographics, anthropometric measures, cardiovascular risk factors, comorbid conditions, and cardiovascular drug therapy collected. MAU prevalence was determined by a stepwise logistic regression analysis with cardiovascular risk factors as univariate., Results: In the univariate analysis, MAU prevalence systematically increased with body mass index (BMI) from 54.4% (1st tertial) to 62.1% (3rd tertial) (p < 0.0001), an increase which was also observed for waist circumference (WC). At any level of BMI, MAU increased with WC from 53.5%, 54.8%, and 55.0% (1st tertial of WC in all three BMI tertials) to 61.4%, 62.1%, and 64.0% (3rd tertial of WC in all BMI tertials) (p < 0.0001). In the multivariate analysis, WC, but not BMI was independently associated with MAU. Furthermore, overweight/obesity were associated with the presence of modifiable and nonmodifiable risk factors., Conclusion: An abnormal WC, but not BMI appears to be independently associated with MAU, an early marker of cardiovascular and renal risk. Increasing WC confers an incremental risk for MAU at any level of BMI, underlining the prognostic importance of abdominal fat accumulation beyond general obesity.

Background: Microalbuminuria (MA) is a risk marker for diabetic nephropathy and cardiovascular (CV) disease (CVD) in patients with diabetes. This study aimed to describe the prevalence of albuminuria, CV risk factors, and treatments for renal and CV protection in an Asian population with type 2 diabetes., Methods: This cross-sectional study conducted in eight Asian countries enrolled normotensive/hypertensive adults with type 2 diabetes without known proteinuria and/or non-diabetic kidney disease. Exclusion criteria were type 1 diabetes, menstruation, pregnancy, and acute fever. A single random urinary albumin/creatinine test was carried out in all patients., Results: Of 8,561 patients, 14% had diabetic retinopathy, and 17% and 21% had history of CV disease and smoking, respectively. Normoalbuminuria was seen in 44%, MA in 44%, and macroalbuminuria in 12%. Target glycosylated hemoglobin (HbA1c) (<7%) was reached in only 37% of 3,834 patients with available values. Diabetes was managed by diet alone in 6%, while others received oral hypoglycemic drugs and/or insulin. In total, 75% did not reach target blood pressure (BP) of

Background: Microalbuminuria (MAU) is an indicator of impaired renal function and a relevant risk predictor for cardiovascular events. An increased heart rate is closely correlated with increased cardiovascular mortality. The International Survey Evaluating Microalbuminuria Routinely by Cardiologists in Patients with Hypertension (I-SEARCH) investigated 21 050 patients with hypertension and risk factors for cardiovascular disease. In patients in sinus rhythm (n = 18 900) the relationship between increased heart rate and the prevalence of MAU was analysed., Methods and Results: The study was performed in 26 countries worldwide from September 2005 to March 2006. Heart rate, blood pressure, urine albumin and serum creatinine were measured as key parameters. With increasing heart rate (> 80 bpm to < 120 bpm) the proportion of patients with MAU increased from 63 to 69% (P < 0.0001). The odds ratio (OR) for MAU increased with increasing heart rate [heart rate 80-100 bpm compared with 60 bpm: OR, 1.47; 95% confidence interval (CI), 1.29-1.68; P < 0.0001; and heart rate 100-120 bpm compared with 60 bpm: OR, 1.56; 95% CI, 1.22-1.99; P = 0.0004]. The prevalence of MAU was similar whether or not patients were receiving beta-blockers; but MAU was significantly reduced in physically active patients compared with sedentary patients (OR, 0.78; 95% CI, 0.73-0.84; P < 0.0001)., Summary: These results show that heart rate is an independent predictor for the prevalence of MAU in hypertensive patients with cardiovascular risk factors. In contrast to beta-blocker therapy, physical activity markedly decreased MAU with increasing heart rates. Further controlled and prospective studies are needed to show that lowered heart rates in combination with MAU can significantly reduce kidney damage, as well as cardiovascular events.

Objectives: To define the prevalence of microalbuminuria (MAU) in hypertensive outpatients attending a cardiologist or internist (i-SEARCH A) and to compare hypertensive outpatients with or without coronary artery disease (CAD; i-SEARCH B). A secondary objective was to establish a correlation between MAU and known cardiovascular risk factors., Methods: i-SEARCH was an international, observational study. which enrolled consecutive outpatients with hypertension. Patients with reasons for a false-positive MAU test were excluded. Main outcome measures were the prevalence of MAU as assessed using a dipstick test, hypertension co-morbidities, co-medication and presence of known cardiovascular risk factors., Results: A total of 21,050 patients, from 26 countries, were included in the primary analysis. Overall prevalence of MAU was 58.4% (men > women), although there was considerable variation in prevalence across countries and continents (maximum 71% in Vietnam/Indonesia; minimum 53% in Germany/Switzerland). In multivariate analyses, predictors of MAU were identified to be male gender, high waist circumference, systolic blood pressure >or= 120 mmHg, diastolic blood pressure >or= 100 mmHg, creatinine clearance >or= 50 ml/min, and the presence of diabetes, congestive heart failure, CAD, history of cerebral pathology, peripheral arterial disease, dyspnoea or palpitations. MAU was present more often in patients with CAD than in patients without., Conclusions: MAU is extremely common in hypertensive outpatients worldwide, especially in patients with known cardiovascular risk factors. Given its importance as a strong, early and independent marker of increased cardiovascular risk in hypertension, the results of i-SEARCH mandate more rigorous MAU screening of hypertensive patients in clinical practice.

Background: The transition of albumin from the vascular lumen into the surrounding tissue always indicates a serious disturbance of the vascular wall. Clinically, this process can be recognized as "cotton-wool" spots of the retina or by testing the urine for the presence of albumin. The appearance of albumin in the urine is pathologic and should be evaluated within the context of the accompanying cardiovascular risk., Pathophysiology and Definitions: Albumin transition is indicative of a disturbance of the barrier function of endothelial cells. In the kidney, damage to podocytes, mesangial and endothelial cells, a loss of charge selectivity, and an altered expression of matrix proteins can be observed. However, vascular alterations are not confined to the kidney but can also be observed in the myocardium. Even though thresholds for microalbuminuria (> 30 mg/24 h) and proteinuria (> 300 mg/24 h) have been arbitrarily defined, an increase in risk starts at much lower levels of albumin excretion., Prevalence and Prognostic Importance: The prevalence of microalbuminuria in the general population is about 8%. However, prevalence rates of > 50% have been observed in high-risk groups, which are accompanied by an increased risk for cardiovascular morbidity and mortality., Therapeutic Options: A number of therapeutic options (tight blood sugar control, blood pressure reduction, lipid lowering) lead to a reduction of albuminuria and an improvement in cardiovascular prognosis. This has particularly been described for renin-angiotensin-aldosterone system-(RAAS-)blocking agents. Their use is not only associated with a reduced risk of end-organ damage (heart failure, diabetic nephropathy, cerebrovascular events) but has been described to decrease mortality as well., Recommendation: A timely diagnosis, a consecutive cardiovascular diagnostic work-up and the subsequent use of RAAS-blocking agents is indicated in patients in whom albuminuria has been diagnosed.