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      Parallel Deterioration of Albuminuria, Arterial Stiffness and Left Ventricular Mass in Essential Hypertension: Integrating Target Organ Damage

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          Abstract

          Background: Albuminuria, arterial stiffening and left ventricular hypertrophy (LVH) constitute target organ damage. We estimated whether increased urinary albumin excretion, assessed by albumin-to-creatine ratio (ACR), and carotid to femoral pulse wave velocity (c-f PWV) were accompanied by augmented left ventricular (LV) mass index (LVMI) in hypertension. Methods: In 428 non-diabetic untreated hypertensives (257 men, mean age = 52 years, office blood pressure (BP) = 146/93 mm Hg) the distributions of ACR and c-f PWV were split by the median (8 mg/g and 7.8 m/s, respectively). Results: Age, male sex, 24 h systolic BP, ACR and c-f PWV were the independent predictors of LVMI ( R<sup>2</sup> = 0.478, p < 0.0001). Among patients with low ACR (n = 198), those with high c-f PWV (n = 84) compared to those with low c-f PWV (n = 114) were characterized by increased LVMI (by 8.9 g/m<sup>2</sup>, p = 0.012) and prevalence of LVH (30 vs. 14%, p = 0.015). Similarly among patients with high ACR (n = 230), those with high c-f PWV (n = 123) compared to those with low c-f PWV (n = 107) exhibited heightened LVMI (by 13.6 g/m<sup>2</sup>, p = 0.001). Conclusions: Increased ACR in conjunction with pronounced arterial stiffness is accompanied by augmented LV mass and higher LVH rates. Furthermore, the interrelationships between albuminuria, c-f PWV and LVMI suggest parallel target organ damage progression.

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          Left ventricular hypertrophy and clinical outcomes in hypertensive patients.

          The prevalence of left ventricular hypertrophy (LVH) rises with severity of hypertension (HT), age, and obesity. Its prevalence ranges from 20% in mildly hypertensive patients to almost 100% in those with severe or complicated HT. However, the diagnosis of LVH is not straightforward, and the definitions and criteria used in clinical studies lack consistency. While many factors play a role in the onset and progression of LVH, blood pressure (BP) is recognized as a central factor. Twenty-four-hour BP measurements are more closely related to LVH than conventional BP readings taken in the clinician's office. Increased renin-angiotensin system (RAS) activity also plays an important role in the development of LVH, and various studies show a correlation between plasma renin activity and left ventricular mass (LVM). LVH is a recognized marker of HT-related target organ damage, and a strong and independent risk factor for adverse cardiovascular (CV) outcomes. CV risk increases with increasing LVM, and decreases with regression of LVH in response to antihypertensive treatment. Therefore the detection, prevention, and reversal of LVH are important goals in HT management. Most antihypertensive drugs can attenuate BP and LVH. However, each drug class may induce LVH regression to a different extent and these extents seldom correlate with the degree of BP reduction achieved. Data from the few large comparative studies in this area suggest that certain classes of antihypertensive drugs and/or their combinations are more effective than others. In particular, calcium channel blockers and drugs that target the RAS, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), appear to have a specific effect on LVH, independent of BP reduction. Guidelines, therefore, have recommended these drug classes for the treatment of hypertensive patients with LVH.
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            Relation of microalbuminuria to adiponectin and augmented C-reactive protein levels in men with essential hypertension.

            Microalbuminuria, and recently, hypoadiponectinemia, have been associated with progression of atherosclerotic disease and increased cardiovascular risk. We examined the possible associations of urinary albumin excretion, expressed as the ratio of albumin to creatinine (ACR), with plasma adiponectin and high-sensitivity C-reactive protein (hs-CRP) levels in men who had essential hypertension. The study population consisted of 108 men who did not have diabetes and were newly diagnosed with stage I to II essential hypertension (age 44.6 years, office blood pressure 148/95 mm Hg) and 110 men matched according to age and body mass index as controls. According to ACR values, which were determined as the average of 2 nonconsecutive overnight spot urine samples, subjects who had hypertension were categorized into 2 groups: those who had microalbuminuria (n = 28; mean ACR 30 to 300 mg/g) and those who had normal albuminuria (n = 80; mean ACR <30 mg/g). Subjects who had hypertension compared with controls exhibited higher ACR and log hs-CRP levels and a trend toward lower log adiponectin values (p = 0.062), whereas those who had normal albuminuria compared with controls had similar log adiponectin levels but significantly higher levels of ACR and log hs-CRP. Moreover, subjects who had hypertension and microalbuminuria compared with those who had hypertension and normal albuminuria had higher log hs-CRP and lower log adiponectin concentrations independently of confounding factors. Among those who had hypertension, ACR exhibited an independent positive correlation with log hs-CRP and a negative correlation with log adiponectin. Multiple linear regression analysis showed that age, body mass index, systolic blood pressure, log hs-CRP, and log adiponectin were significant independent predictors of the ACR. In conclusion, microalbuminuria is accompanied by decreased adiponectin and increased hs-CRP levels in the setting of essential hypertension, reflecting a rather diffuse atherosclerotic process.
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              Microalbuminuria in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study.

              Left ventricular hypertrophy and albuminuria have both been shown to predict increased cardiovascular morbidity and mortality. However, the relationship between these markers of cardiac and renal glomerular damage has not been evaluated in a large hypertensive population with target organ damage. The present study was undertaken to determine whether albuminuria is associated with persistent electrocardiographic (ECG) left ventricular hypertrophy, independent of established risk factors for cardiac hypertrophy, in a large hypertensive population with left ventricular hypertrophy who were free of overt renal failure. Patients with stage II-III hypertension were enrolled in the study if they had left ventricular hypertrophy on a screening ECG by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria, and clinic blood pressures between 160 and 200/95-115 mmHg and plasma creatinine 3.5 mg/mmol and macroalbuminuria if UACR > 35 mg/mmol. The mean age of the 8029 patients was 66 years, 54% were women. Microalbuminuria was found in 23% and macroalbuminuria in 4% of patients. Microalbuminuria was more prevalent in patients of African American (35%), Hispanic (37%) and Asian (36%) ethnicity, heavy smokers (32%), diabetics (36%) and in patients with ECG left ventricular hypertrophy by both ECG-criteria (29%). Urine albumin/creatinine was positively related to Sokolow-Lyon voltage criteria and Cornell voltage-duration product criteria. In multiple regression analysis, higher UACR was independently associated with older age, diabetes, higher blood pressure, serum creatinine, smoking and left ventricular hypertrophy. Patients smoking > 20 cigarettes/day had a 1.6-fold higher prevalence of microalbuminuria and a 3.7-fold higher prevalence of macroalbuminuria than never-smokers. ECG left ventricular hypertrophy by Cornell voltage-duration product or Sokolow-Lyon criteria was associated with a 1.6-fold increased prevalence of microalbuminuria and a 2.6-fold increase risk of macroalbuminuria compared to no left ventricular hypertrophy on the second ECG. In patients with moderately severe hypertension, left ventricular hypertrophy on two consecutive ECGs is associated with increased prevalences of micro- and macroalbuminuria compared to patients without persistent ECG left ventricular hypertrophy. High albumin excretion was related to left ventricular hypertrophy independent of age, blood pressure, diabetes, race, serum creatinine or smoking, suggesting parallel cardiac damage and albuminuria.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2011
                August 2011
                08 June 2011
                : 119
                : 1
                : c27-c34
                Affiliations
                aFirst Cardiology Clinic, University of Athens, Hippokration Hospital, bDepartment of Cardiology, Western Attica General Hospital, cDepartment of Cardiology, Sismanogleio General Hospital, and dDepartment of Cardiology, Laiko Hospital, Athens, Greece
                Author notes
                *Costas Tsioufis, MD, PhD, FESC, FACC, 3, Kolokotroni Street, GR–15236 P. Penteli, Athens (Greece), Tel. +30 210 613 1393, E-Mail ktsioufis@hippocratio.gr
                Article
                324215 Nephron Clin Pract 2011;119:c27–c34
                10.1159/000324215
                21654180
                cb1e192f-3478-4de0-9b56-536044fd6286
                © 2011 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 09 September 2010
                : 07 January 2011
                Page count
                Figures: 2, Tables: 4, Pages: 8
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Albuminuria,Hypertension,Arterial stiffness,Left ventricular mass

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