Showing papers by "Roland E. Schmieder published in 2010"

Inhibition of Prolyl Hydroxylases Increases Erythropoietin Production in ESRD

Abstract: The reasons for inadequate production of erythropoietin (EPO) in patients with ESRD are poorly understood. A better understanding of EPO regulation, namely oxygen-dependent hydroxylation of the hypoxia-inducible transcription factor (HIF), may enable targeted pharmacological intervention. Here, we tested the ability of fibrotic kidneys and extrarenal tissues to produce EPO. In this phase 1 study, we used an orally active prolyl-hydroxylase inhibitor, FG-2216, to stabilize HIF independent of oxygen availability in 12 hemodialysis (HD) patients, six of whom were anephric, and in six healthy volunteers. FG-2216 increased plasma EPO levels 30.8-fold in HD patients with kidneys, 14.5-fold in anephric HD patients, and 12.7-fold in healthy volunteers. These data demonstrate that pharmacologic manipulation of the HIF system can stimulate endogenous EPO production. Furthermore, the data indicate that deranged oxygen sensing—not a loss of EPO production capacity—causes renal anemia.

End organ damage in hypertension.

Abstract: SUMMARY Background: End organ damage in hypertension can be detected early, reflects accurately the hypertensive patient’s overall cardiovascular risk, and should be prevented and treated with antihypertensive treatment. Method: We selectively review the relevant literature since 1995, including the German and European guidelines for the diagnosis and treatment of arterial hypertension. Results: Measurement of the intima-media thickness in the common carotid artery and of the pulse-wave velocity is now recommended for the early diagnosis of hypertensive vasculopathy. Left ventricular hypertrophy, an impor tant component of hypertensive heart disease, can be diagnosed by echocardiography and with the aid of new electrocardiographic indices. Early signs of hypertensive nephropathy, namely albuminuria and a decreased glomerular filtration rate, are prognostically valuable and easy to detect. Cerebrovascular damage, including early microangiopathic changes, is best diagnosed by magnetic resonance imaging. The treatment of end organ damage due to hypertension centers on blood pressure reduction. Blockade of the renin angiotensin-aldosterone system is an essential part of the treatment of early end organ damage. Conclusion: Hypertensive end organ damage can now be diagnosed early and reversed with specific and aggressive treatment. ►Cite this as:

Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals.

Abstract: ObjectivesWe studied the urinary proteome in a total of 623 individuals with and without coronary artery disease (CAD) in order to characterize multiple biomarkers that enable prediction of the presence of CAD.MethodsUrine samples were analyzed by capillary electrophoresis coupled online to micro ti

Candesartan improves blood pressure control and reduces proteinuria in renal transplant recipients: results from SECRET

Abstract: Background. Hypertension is a risk factor for the two leading causes of death in renal transplant recipients: cardiovascular disease (CVD) and graft failure. Despite this, the optimum medication for post-transplant hypertension is unclear. Methods. The Study on Evaluation of Candesartan Cilexetil after Renal Transplantation (SECRET) was an international multicentre, double-blind, randomized investigation of the angiotensin II type 1 receptor blocker (ARB) candesartan cilexetil versus placebo in renal allograft recipients originally designed to study 700 patients for 3years. The candesartan dose was escalated from 4 to 16mg daily, followed by addition of co-medication, if needed, with the aim of achieving a diastolic blood pressure (BP) <85 mmHg. The primary efficacy variable was a composite of all-cause mortality, cardiovascular morbidity and graft failure. Results. SECRET was stopped prematurely as the primary event rate was much lower than expected. At that point, 502 patients were enrolled; 255 received candesartan and 247 placebo. Thirteen primary events had occurred in each group. Control of both systolic and diastolic BP was better in the candesartan group. Urinary protein excretion and protein/creatinine ratio decreased on candesartan but increased on placebo. Serum creatinine and potassium were increased in candesartan patients, but these changes were generally small. Conclusions. SECRET provides insights into the design and conduct of studies in this area and evidence for the utility of candesartan, which showed good safety and tolerability, improved BP control and decreased proteinuria in renal transplant recipients.

Measurement of kidney perfusion by magnetic resonance imaging: comparison of MRI with arterial spin labeling to para-aminohippuric acid plasma clearance in male subjects with metabolic syndrome.

Abstract: BACKGROUND Magnetic resonance imaging with arterial spin labeling (MRI-ASL) is a non-invasive approach to measure organ perfusion. We aimed to examine whether MRI-ASL kidney perfusion measurements are related to measurements of renal plasma flow (RPF) by para-aminohippuric acid (PAH) plasma clearance and whether changes of kidney perfusion in response to treatment with telmisartan can be detected by MRI-ASL. METHODS Twenty-four patients with metabolic syndrome and an estimated creatinine clearance according to Cockroft and Gault of > or =60 ml/min were included in the study. Kidney perfusion was assessed by MRI-ASL measurements of a single coronal kidney slice (with flow-sensitive alternating inversion recovery and true fast imaging with steady-state processing sequence) and by measurements of RPF using PAH plasma clearance before and after 2 weeks of treatment with the angiotensin receptor blocker telmisartan. All MRI-ASL examinations were performed on a 1.5 T scanner. RESULTS Two weeks of therapy with telmisartan led to a significant increase of RPF (from 313 +/- 47 to 348 +/- 69 ml/min/m, P = 0.007) and MRI-ASL kidney perfusion measurements (from 253 +/- 20 to 268 +/- 25 ml/min/100 g, P = 0.020). RPF measurements were related with MRI-ASL kidney perfusion measurements (r = 0.575, P < 0.001). Changes of RPF measurements and changes of MRI-ASL kidney perfusion measurements in response to treatment with telmisartan revealed a close relationship when expressed in absolute terms (r = 0.548, P = 0.015) and in percentage changes (r = 0.514, P = 0.025). CONCLUSIONS Perfusion measurement of a single coronal kidney slice by MRI-ASL is able to approximate kidney perfusion and to approximate changes in kidney perfusion due to pharmacological intervention.

Urinary Collagen Fragments Are Significantly Altered in Diabetes: A Link to Pathophysiology

Abstract: Background: The pathogenesis of diabetes mellitus (DM) is variable, comprising different inflammatory and immune responses. Proteome analysis holds the promise of delivering insight into the pathophysiological changes associated with diabetes. Recently, we identified and validated urinary proteomics biomarkers for diabetes. Based on these initial findings, we aimed to further validate urinary proteomics biomarkers specific for diabetes in general, and particularity associated with either type 1 (T1D) or type 2 diabetes (T2D). Methodology/Principal Findings: Therefore, the low-molecular-weight urinary proteome of 902 subjects from 10 different centers, 315 controls and 587 patients with T1D (n=299) or T2D (n=288), was analyzed using capillary-electrophoresis mass-spectrometry. The 261 urinary biomarkers (100 were sequenced) previously discovered in 205 subjects were validated in an additional 697 subjects to distinguish DM subjects (n=382) from control subjects (n=315) with 94% (95% CI: 92–95) accuracy in this study. To identify biomarkers that differentiate T1D from T2D, a subset of normoalbuminuric patients with T1D (n=68) and T2D (n=42) was employed, enabling identification of 131 biomarker candidates (40 were sequenced) differentially regulated between T1D and T2D. These biomarkers distinguished T1D from T2D in an independent validation set of normoalbuminuric patients (n=108) with 88% (95% CI: 81–94%) accuracy, and in patients with impaired renal function (n=369) with 85% (95% CI: 81–88%) accuracy. Specific collagen fragments were associated with diabetes and type of diabetes indicating changes in collagen turnover and extracellular matrix as one hallmark of the molecular pathophysiology of diabetes. Additional biomarkers including inflammatory processes and pro-thrombotic alterations were observed. Conclusions/Significance: These findings, based on the largest proteomic study performed to date on subjects with DM, validate the previously described biomarkers for DM, and pinpoint differences in the urinary proteome of T1D and T2D, indicating significant differences in extracellular matrix remodeling.

Improvement of hypertension management by structured physician education and feedback system: cluster randomized trial:

Abstract: IntroductionWe aimed to assess whether hypertension management with a structured physician information program and a feedback system leads to improved blood pressure (BP) control and cardiovascular outcomes.MethodsCluster randomized (3: 1), open, monitored, multicenter trial in Germany. Primary care-based physicians in the information group (IG) received detailed training on hypertension guidelines, feedback on target-level attainment, and a reminder to intensify treatment after each patient visit, whereas the observation/control group (CG) did not receive any such measures. A three-level mixed model was developed. Time-independent level differences between groups, group-independent changes, and nonparallel group-specific changes over time were tested.ResultsA total of 15 041 (78.1%) hypertensive patients were in the IG and 4213 (21.9%) in the CG. By 1-year follow-up, 82.9% of patients in the IG and 81.5% in the CG remained in the study. The guideline-oriented BP target was attained by 56.8% in the IG and...

Renal resistive index in addition to low-grade albuminuria complements screening for target organ damage in therapy-resistant hypertension.

Abstract: ObjectiveWe examined the value of renal resistive index (RRI) for prevalence of cardiovascular target organ damage in therapy-resistant hypertension in comparison to low-grade albuminuria.MethodsEighty-four patients with therapy-resistant hypertension (age 59.7 ± 8.1 years) were screened for cardiov

Renal protection in diabetes: lessons from ONTARGET ®

Abstract: Hypertension is an important independent risk factor for renal disease. If hypertension and chronic renal disease co-exist, as is common in patients with diabetes mellitus, the risk of cardiovascular disease is heightened. The importance of rigorous blood pressure control is recognized in current guidelines, with a recommended target of office blood pressure of < 130/80 mmHg; although ambulatory blood pressure may be more appropriate in order to identify the 24-hour hypertensive burden. Even lower blood pressure may further reduce the progression of chronic kidney disease, but the incidence of cardiovascular events may increase. Albuminuria not only indicates renal damage, but is also a powerful predictor of cardiovascular morbidity and mortality at least in patients with high cardiovascular risk and potentially pre-existing vascular damage. Management of the multiple factors for renal and cardiovascular disease is mandatory in the diabetic patient. The renin-angiotensin system (RAS) plays a pivotal role in the progression of renal disease, as well as in hypertension and target-organ damage. The use of agents that target the RAS confer renoprotection in addition to antihypertensive activity. There is extensive evidence of the renoprotective effect of angiotensin II receptor blockers (ARBs), and specifically telmisartan. In addition to providing 24-hour blood pressure control, clinical studies in patients with diabetes show that telmisartan improves renal endothelial function, prevents progression from microalbuminuria to macroalbuminuria, slows the decline in glomerular filtration rate and reduces proteinuria in overt nephropathy. These effects cannot be solely attributed to blood pressure control. In contrast to other members of the ARB class, the renoprotective effect of telmisartan is not confined to the management of diabetic nephropathy; slowing the progression of albuminuria has been demonstrated in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET®), which included diabetic and non-diabetic patients at high risk of cardiovascular events.

Arterial stiffness and pulse wave analysis

Abstract: Institut 1 Herausgegeben von der Gesellschaft für Arterielle Gefäßsteifigkeit, Deutschland-Österreich-Schweiz (DeGAG) in Kooperation mit der Österreichischen Gesellschaft für Hypertensiologie (ÖGH), der Schweizerischen Hypertonie Gesellschaft (SHG), der International Prevention Organization (IPO), der Deutschen Gesellschaft für Nephrologie (DGfN) und der Deutschen Gesellschaft für Angiologie Gesellschaft für Gefäßmedizin (DGA)

Aliskiren Monotherapy Does Not Cause Paradoxical Blood Pressure Rises Meta-Analysis of Data From 8 Clinical Trials

Abstract: Angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and diuretics all cause reactive rises in plasma renin concentration, but particularly high levels have been reported with aliskiren. This prompted speculation that blockade of plasma renin activity with aliskiren could be overwhelmed, leading to paradoxical increases in blood pressure. This meta-analysis of data from 4877 patients from 8 randomized, double-blind, placebo- and/or active-controlled trials examined this hypothesis. The analysis focused on the incidence of paradoxical blood pressure increases above predefined thresholds, after ≥4 weeks of treatment with 300 mg of aliskiren, angiotensin receptor blockers (300 mg of irbesartan, 100 mg of losartan, or 320 mg of valsartan), 10 mg of ramipril, 25 mg of hydrochlorothiazide, or placebo. There were no significant differences in the frequency of increases in systolic (>10 mm Hg; P =0.30) or diastolic (>5 mm Hg; P =0.65) pressure among those treated with aliskiren (3.9% and 3.1%, respectively), angiotensin receptor blockers (4.0% and 3.7%), ramipril (5.7% and 2.6%), or hydrochlorothiazide (4.4% and 2.7%). Increases in blood pressure were considerably more frequent in the placebo group (12.6% and 11.4%; P 10 mm Hg that was associated with an increase in plasma renin activity >0.1 ng/mL per hour. In conclusion, the incidence of blood pressure increases with aliskiren was similar to that during treatment with other antihypertensive drugs. Blood pressure rises on aliskiren treatment were not associated with increases in plasma renin activity. This meta-analysis found no evidence that aliskiren uniquely causes paradoxical rises in blood pressure.

Renal resistive index—a valid tool to assess renal endothelial function in humans?

Abstract: Background In humans, renal endothelial function is assessed by the vasoconstrictive response to L-NG-monomethyl arginine (L-NMMA). We hypothesized that Doppler sonographic measurements of the renal resistive index in response to inhibition of nitric oxide synthase offer a new methodological approach for testing renal endothelial function. Methods Forty-one patients without nephropathy were included. Para-aminohippurate and inulin clearance were performed under basal conditions and during L-NMMA infusion. In parallel, renal resistive index was assessed by Doppler sonography, and central blood pressure was determined. Results Following nitric oxide synthase inhibition, renal resistive index increased significantly, and 29% of our patients developed Doppler sonographic diastolic zero flow. Renal plasma flow decreased in response to L-NMMA, and conversely, renal vascular resistance increased. There was no correlation of renal vascular resistance and renal resistive index at baseline and during nitric oxide synthase inhibition. Changes in renal resistive index were not related to changes in renal perfusion or renal vascular resistance. Renal resistive index correlated with central pulse pressure at baseline and during L-NMMA infusion, whereas renal vascular resistance did not correlate with central pulse pressure. Conclusion Our data do not support the hypothesis that renal resistive index is a tool to test renal endothelial function in humans and should not be used interchangeably with renal vascular resistance.

The role of fixed-dose combination therapy with drugs that target the renin-angiotensin system in the hypertension paradigm.

Abstract: Most patients with hypertension require two or more agents from different classes to achieve BP control. Several fixed-dose combinations are available, often combining agents that target the renin angiotensin system (angiotensin-converting enzyme [ACE] inhibitors or an angiotensin receptor blockers [ARBs]) plus either thiazide diuretics or calcium channel blockers (CCBs). At low doses, these combinations may have greater efficacy and better tolerability than the respective high dose monotherapies. Combining an ARB (instead of an ACE inhibitor) with the CCB amlodipine offers efficacy with improved tolerability. This review aims to highlight the simplicity, tolerability, and convenience of fixed-dose combinations targeting the renin-angiotensin system, which can lead to improved compliance and more patients achieving BP goals.

Effectiveness and tolerability of a fixed-dose combination of olmesartan and amlodipine in clinical practice

Abstract: Objectives: To assess the efficacy and tolerability of a fixed-dose combination of olmesartan and amlodipine in an unselected population of patients in primary care and to compare the results with recent randomized controlled trial evidence.

Dihydropyridine calcium antagonists are associated with increased albuminuria in treatment-resistant hypertensives

Abstract: ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) are superior to dihydropyridine calcium-antagonists (DHP) with regard to reduction of albuminuria in patients with diabetic nephropathy. It has been argued that with blood pressure outside the targets DHP may exaggerate albuminuria in hypertensive patients. We addressed the question in an observational study in patients with difficult-to-treat essential hypertension. We analyzed baseline data from patients (n=80) screened for a clinical trial in treatment-resistant hypertension. All patients were treated with an ACEI/ARB, a diuretic and at least a third drug in the highest tolerated dose. We compared 50 patients who were treated with DHPs with 30 who were not. Albuminuria was assessed as albumin excretion in 24-hour urine. Values are given as mean ± SD. All comparisons were made using unpaired t-test. There were no differences with regard to demographic parameters, blood pressure or duration of hypertension between both groups. Albumin excretion was 14.3 ± 16.9 mg/d in patients treated with DHPs and 8.5 ± 6.6 mg/d in patients treated without DHPs (p=0.036). Our data indicate that even in patients treated with ACEI/ARBs DHPs are associated with increased albuminuria. Since increases of albuminuria even in the low range are associated with increased cardiovascular risk, detection of albuminuria should influence the choice of antihypertensive drugs in hypertensive patients with albuminuria.

Improving quality of life in hypertension management using a fixed-dose combination of olmesartan and amlodipine in primary care.

Abstract: Objectives. To assess quality of life (QoL) in unselected patients in primary care treated with a fixed-dose combination of olmesartan and amlodipine. Research design and methods. Multicenter, noninterventional, noncontrolled observational study in 8241 patients seen by 2187 physicians over 12 – 18 weeks. Main outcome measures. Changes in QoL were assessed by using the Short Form 12 (SF-12) questionnaire completed by 5434 patients (65.9%) at baseline and 4924 patients (59.8%) at the follow-up visit. Results. Patients had a mean age of 62.8 ± 11.8 years (48.1% female), mean blood pressure [BP] at baseline was 161.8 ± 16.6/93.6 ± 10.2 mmHg and 74.8% had at least one co-morbid risk factor or condition. All 12 items of the SF-12 improved over the observational period (p < 0.0001) as did the physical (46.8 vs 40.4; p < 0.0001) and mental summary scores (52.4 vs 47.5; p < 0.0001). Correlations of changes in systolic and diastolic BP, pulse pressure and heart rate with scores were significant, although weak (max...

Europejskie zalecenia dotycza̧ce leczenia nadciśnienia tȩtniczego: Stanowisko Europejskiego Towarzystwa Nadciśnienia Tȩtniczego 2009

Abstract: Adresy do korespondencji: Professor Giuseppe Mancia, Clinica Medica, University of Milan-Bicocca, San Gerardo Hospital, Via Pergolesi 33, 20052 Monza, Milan, Włochy tel.: +39 039 2333357; faks: +39 039 322274; e-mail: giuseppe.mancia@unimib.it Professor Stéphane Laurent, Department of Pharmacology and INSERM U970, European Hospital Georges Pompidou, Paris Descartes University, 20 rue Leblanc, 75015 Paris, Francja tel.: +33 1 56 09 39 91; faks: +33 1 56 09 39 92; e-mail: stephane.laurent@egp.ap-hop.-paris.fr

Change in augmentation index during NOS inhibition, an index of basal NO production, is an independent determinant of large-artery function.

Abstract: Background/Aims: Arterial wave reflection, measured as augmentation index (AIx), and central pulse pressure (PP) closely predict cardiovascular events. We hypothesized that basal nitric oxide (NO) production would be a determinant of AIx and central PP. Methods: AIx and central PP were assessed at baseline by pulse wave analysis in 86 male subjects across a wide range of age, blood pressure and lipid values. The basal NO production in the cardiovascular system was then determined as change in AIx during NO synthase blockade with NG-monomethyl-L-arginine (L-NMMA, 3.25 mg/kg). Results: AIx increased from 17.5 ± 14.6 to 23.1 ± 14.2 during L-NMMA infusion (p L-NMMA is a strong and independent determinant of baseline central AIx, central PP and PP amplification. Conclusion: Greater change of AIx to L-NMMA, an index of basal NO production, is associated with better large-artery function. Therefore, therapeutic interventions which increase the basal NO production might be particularly effective in reducing cardiovascular risk.

Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 subjects: 6b.07

Abstract: Objective: We studied the urinary proteome in a total of 623 subjects with and without coronary artery disease (CAD) in order to characterize multiple biomarkers that enable prediction of the presence of CAD. Design and Method: We recruited a total of 138 subjects specifically for this study. The cohort included 71 patients with severe CAD and 67 control subjects. CE-MS analysis was performed with a P/ACE MDQ capillary electrophoresis system coupled online to micro-TOF-MS. Results: The panels we established before (Zimmerli et al. [2008] and v.z. Muhlen et al. [2009]) revealed significant ability to predict CAD in a blinded analysis of 138 urine samples from 71 patients with CAD and 67 healthy individuals with areas under the curve (AUC) of 68% (95% CI 59–76%; P < 0.0001) and 77% (95% CI 69–84%; P < 0.0001), respectively. A larger cohort comparison in 586 samples from 408 subjects allowed the definition of an extended pattern of 238 CAD-specific polypeptides. This pattern provided an improved identification of patients with CAD in the blinded cohort (AUC=87% [95% CI 81–92%; P < 0.0001]) compared to the panels established by Zimmerli et al. (P < 0.0001) and v.z. Muhlen et al. (P = 0.009). The sequences of the 238 discriminatory polypeptides include fragments of alpha-1-antitrypsin, collagen type 1 and 3, granin-like neuroendocrine peptide precursor, membrane associated progesterone receptor component 1, sodium/potassium-transporting ATPase gamma chain, and fibrinogen-alpha-chain. Several biomarkers changed significantly towards the healthy signature in patients receiving Irbesartan 300 mg once daily for 2 years compared to placebo (n = 11 each) whereas short term (10 weeks) treatment with irbesartan (n = 55) did not significantly affect the polypeptide pattern. Conclusions: Our results confirm that urinary proteomics can identify CAD patients with high confidence and might be useful for monitoring the effects of therapeutic interventions.

Role of the angiotensin II type 2 receptor gene (+1675G/A) polymorphism on left ventricular hypertrophy and geometry in treated hypertensive patients

Abstract: ObjectiveA genetic polymorphism in the angiotensin II type 2 receptor (AGTR2 +1675G/A) has been associated with left ventricular hypertrophy (LVH). We tested whether this polymorphism affects LVH and left ventricular geometry parameters in patients with essential hypertension and cardiovascular dise

Telmisartan and hydrochlorothiazide combination therapy for the treatment of hypertension

Abstract: Background:Control of elevated blood pressure has been shown to reduce the risk of cardiovascular events. The angiotensin II receptor blocker (ARB), telmisartan, has been shown to provide effective 24-hour blood pressure control. Additional antihypertensive efficacy can be achieved by combining telmisartan with the thiazide diuretic hydrochlorothiazide (HCTZ).Objective:To review the clinical data in combination therapy with telmisartan and HCTZ.Methods:Search of Medline and Embase for published clinical studies using the keywords telmisartan and HCTZ.Findings:The telmisartan/HCTZ combination provides significant reductions in blood pressure, effective 24-hour blood pressure control and is well-tolerated. Blood pressure reductions with this combination are greater than those achieved with either drug alone, and in comparative studies telmisartan/HCTZ is more effective than other ARB/HCTZ combinations. However, it should be noted that some of the combinations assessed used doses of the drugs that we...

Agreement within Europe about antihypertensive treatment and education - results from the European Society of Hypertension questionnaire.

Abstract: Agreement within Europe abo ut antihypertensive treatment and education – results from the European Society of Hypertension questionnaire Michael H. Olsen, Jean-Michel Mallion, Karl-Heinz Rahn, Serap Erdine, Margus Viigimaa, Stéphane Laurent, Enrico Agabiti-Rosei, Giuseppe Mancia, Roland E. Schmieder, Renata Cifkova, Anna Dominiczak, Sverre E. Kjeldsen, Josep Redon, Alberto Zanchetti, Peter Nilsson, Krzysztof Narkiewicz, on behalf of the ESH Council

Follow-up of cardiovascular risk markers in hypertensive patients treated with irbesartan: results of the i-SEARCH Plus Registry.

Abstract: J Clin Hypertens (Greenwich). Microalbuminuria (MAU), high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) are risk markers used to predict the prognosis of hypertensive patients; however, they have not been prospectively evaluated in primary care. An investigation was conducted using i-SEARCH Plus, a registry documenting 1649 patients with hypertension who received irbesartan at office-based cardiologists over 12 months. Mean age at baseline was 61.4±11.3 years, 43.2% were women, and blood pressure was 159.8±20.1/93.4±11.9 mm Hg. Median albumin/creatinine ratio (ACR) at baseline was 9.90 (interquartile range [IQR], 5.76--25.52) mg/g, hsCRP 2.46 (IQR, 1.16--5.14) mg/L, and NT-proBNP 89.28 (IQR, 38.63--203.40) pg/mL. In patients with MAU (ACR ≥20 mg/g), the age-adjusted risk of a combined end point of newly diagnosed coronary artery disease (CAD), myocardial infarction, stroke/transitory ischemic attack, and death at 12-month follow-up was increased (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.49–4.76), as was the incidence of CAD (OR, 3.27; 95%CI, 1.39–7.68) and death (OR, 4.63; 95%CI, 1.44–14.94). No correlations with end points were found for hsCRP or NT-proBNP after adjusting for age and the presence of MAU. MAU is an independent predictor of cardiovascular events in hypertensive patients. These findings confirm previous reports on the prognostic value of MAU and establish its incremental value over hsCRP and NT-proBNP. J Clin Hypertens (Greenwich). 2010;12:909–916. © 2010 Wiley Periodicals, Inc.