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      Age, Gender and Load-Related Influences on Left Ventricular Geometric Remodeling, Systolic Mid-Wall Function, and NT-ProBNP in Asymptomatic Asian Population

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          Abstract

          Background

          Advanced age is associated with left ventricle (LV) remodeling and impaired cardiac function that may increase the risk of heart failure. Even so, studies regarding age-related cardiac remodeling in a large, asymptomatic Asian population remain limited.

          Materials and Methods

          We studied 8,410 asymptomatic participants (49.7 ±11.7 y, 38.9% women) in a health evaluation cohort (2004–2012) at a tertiary center in Northern Taiwan. We analyzed age-related alterations for all echocardiography-derived cardiac structures/functions and the associations with circulating N-terminal prohormone of brain natriuretic peptide (NT-proBNP). We also explored sex-related differences in these measures.

          Results

          In our cohort of 8,410 participants, advanced age was associated with greater LV wall thickness, larger LV total mass (+5.08 g/decade), and greater LV mass index (4.41 g/m 2/decade), as well as increased serum NT-proBNP level (+18.89 pg/mL/decade). An accompanying reduction of stress-corrected midwall fractional shortening (–0.1%/decade) with aging was apparent in women after multi-variate adjustment (–0.09%/decade, p = 0.001). Furthermore, women demonstrated greater overall increase in LV wall thickness, LV mass index, and NT-proBNP compared to men ( p for interaction: <0.001). All blood pressure components, including systolic, diastolic, and pulse pressures were independently associated with greater wall thickness and LV mass index after adjustment for confounders (all p <0.001). The associations between age and cardiac remodeling or mid-wall functions were further confirmed in a subset of study subjects with repeated follow up by GEE model.

          Conclusions

          Significant associations of unfavorable LV remodeling and advanced age in our asymptomatic Asian population were observed, along with sex differences. These data may help explain the incidence of some diverse gender-related cardiovascular diseases, especially heart failure.

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          Most cited references30

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          The pathophysiology of heart failure with preserved ejection fraction.

          Approximately half of all patients with heart failure have preserved ejection fraction (HFpEF) and, as life expectancies continue to increase in western societies, the prevalence of HFpEF will continue to grow. In contrast to heart failure with reduced ejection fraction (HFrEF), no treatment has been proven in pivotal clinical trials to be effective for HFpEF, largely because of the pathophysiological heterogeneity that exists within the broad spectrum of HFpEF. This syndrome was historically considered to be caused exclusively by left ventricular diastolic dysfunction, but research has identified several other contributory factors, including limitations in left ventricular systolic reserve, systemic and pulmonary vascular function, nitric oxide bioavailability, chronotropic reserve, right heart function, autonomic tone, left atrial function, and peripheral impairments. Multiple individual mechanisms frequently coexist within the same patient to cause symptomatic heart failure, but between patients with HFpEF the extent to which each component is operative can differ widely, confounding treatment approaches. This Review focuses on our current understanding of the pathophysiological mechanisms underlying HFpEF, and how they might be mechanistically related to typical risk factors for HFpEF, including ageing, obesity, and hypertension.
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            Prevalence and significance of alterations in cardiac structure and function in patients with heart failure and a preserved ejection fraction.

            The purpose of this study was to examine the prevalence of abnormalities in cardiac structure and function present in patients with heart failure and a preserved ejection fraction (HFPEF) and to determine whether these alterations in structure and function were associated with cardiovascular morbidity and mortality. The Irbesartan in HFPEF trial (I-PRESERVE) enrolled 4128 patients; echocardiographic determination of left ventricular (LV) volume, mass, left atrial (LA) size, systolic function, and diastolic function were made at baseline in 745 patients. The primary end point was death or protocol-specific cardiovascular hospitalization. A secondary end point was the composite of heart failure death or heart failure hospitalization. Associations between baseline structure and function and patient outcomes were examined using univariate and multivariable Cox proportional hazard analyses. In this substudy, LV hypertrophy or concentric remodeling was present in 59%, LA enlargement was present in 66%, and diastolic dysfunction was present in 69% of the patients. Multivariable analyses controlling for 7 clinical variables (including log N-terminal pro-B-type natriuretic peptide) indicated that increased LV mass, mass/volume ratio, and LA size were independently associated with an increased risk of both primary and heart failure events (all P<0.05). Left ventricular hypertrophy or concentric remodeling, LA enlargement, and diastolic dysfunction were present in the majority of patients with HFPEF. Left ventricular mass and LA size were independently associated with an increased risk of morbidity and mortality. The presence of structural remodeling and diastolic dysfunction may be useful additions to diagnostic criteria and provide important prognostic insights in patients with HFPEF.
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              Age-related left ventricular remodeling and associated risk for cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis.

              Age-related alterations of left ventricular (LV) structure and function that may predispose to cardiovascular events are not well understood. We used cardiac MRI to examine age-related differences in LV structure and function in 5004 participants without overt cardiovascular disease when enrolled in the Multi-Ethnic Study of Atherosclerosis; 1099 participants received additional strain analyses by MRI tagging. We also assessed the relation of age-associated remodeling with cardiovascular outcomes using Cox proportional hazard models adjusting for cardiovascular risk factors. Although LV mass decreased with age (-0.3 g per year), the mass-to-volume ratio markedly increased (+5 mg/mL per year, P or =65 years; hazard ratio, 1.68 [CI 0.77 to 3.68]) individuals with the highest compared to lowest mass-to-volume ratio quintile (P(interaction)=0.013). Age is associated with a phenotype of LV remodeling marked by increased mass-to-volume ratio and accompanied by systolic as well as diastolic myocardial dysfunction that is not reflected by preserved ejection fraction. This pattern of ventricular remodeling confers significant cardiovascular risk, particularly when present earlier in life.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                9 June 2016
                2016
                : 11
                : 6
                : e0156467
                Affiliations
                [1 ]Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
                [2 ]Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei branch, Taipei City, Taiwan
                [3 ]Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei branch, Taipei City, Taiwan
                [4 ]The Institute of Health Policy and Management, College of Public Health, National Taiwan University, Taipei, Taiwan
                University of Minnesota, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CLH JYK HIY. Performed the experiments: CC CLH. Analyzed the data: CC CCL KTS. Contributed reagents/materials/analysis tools: HIY CLH SCS. Wrote the paper: CC CJYH CLH. Conceptual frame work: HIY.

                Article
                PONE-D-15-49290
                10.1371/journal.pone.0156467
                4900638
                27280886
                90a361ee-2edb-4696-b883-bb95943f1fbe
                © 2016 Chen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 November 2015
                : 13 May 2016
                Page count
                Figures: 3, Tables: 4, Pages: 15
                Funding
                This work was partly supported by grants of the National Science Council (NSC 103-2314-B-010-005-MY3, 103-2314-B-195-001-MY3, 101-2314-B-195 -020 -MY1, MOST 103-2314-B-195-006-MY3), and Mackay Memorial Hospital (10271, 10248, 10220, 10253, 10375, 10358, E-102003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                People and Places
                Population Groupings
                Age Groups
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Ultrasound Imaging
                Echocardiography
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Ultrasound Imaging
                Echocardiography
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Ultrasound Imaging
                Echocardiography
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Cardiac Ventricles
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Cardiac Ventricles
                Medicine and Health Sciences
                Cardiology
                Heart Failure
                Medicine and Health Sciences
                Cardiovascular Medicine
                Cardiovascular Diseases
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Medicine and Health Sciences
                Geriatrics
                Custom metadata
                Owing to local institutional regulation together with the newly applied "Personal Information Protection Act" in Taiwan, the data will not be appropriate to be released in a public place. Data are available from the "Mackay Memorial Hospital" Institutional Data Access / Ethics Committee for researchers who meet the criteria for access to confidential data. The contact information as follows: Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Rd., Taipei City 10449, Taiwan. TEL: 02-25433535#3486~3488, EMAIL: mmhirb82@ 123456gmail.com (Institutional Review Board).

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