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      The Groningen electrocardiographic criteria for left ventricular hypertrophy: a sex-specific analysis

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          Abstract

          The sensitivity of electrocardiogram (ECG) criteria to detect left ventricular hypertrophy (LVH) is low, especially in women. We determined sex-specific sensitivities of ECG-LVH criteria, and developed new criteria, using cardiovascular magnetic resonance imaging (CMR). Sensitivities of ECG-LVH criteria were determined in participants of the UK Biobank (N = 3632). LVH was defined when left ventricular mass was > 95% confidence interval (CI) according to age and sex. In a training cohort (75%, N = 2724), sex-specific ECG-LVH criteria were developed by investigating all possible sums of QRS-amplitudes in all 12 leads, and selecting the sum with the highest pseudo-R 2 and area under the curve to detect LVH. Performance was assessed in a validation cohort (25%, N = 908), and association with blood pressure change was investigated in an independent cohort. Sensitivities of ECG-LVH criteria were low, especially in women. Newly developed Groningen-LVH criterion for women (Q V2 + R I + R V5 + R V6 + S V2 + S V4 + S V5 + S V6) outperformed all ECG-LVH criteria with a sensitivity of 42% (95% CI 35–49%). In men, newly developed criterion ((R I + R V5 + S II + S V2 + S V6) × QRS duration) was equally sensitive as 12-lead sum with a sensitivity of 44% (95% CI 37–51%) and outperformed the other criteria. In an independent cohort, the Groningen-LVH criteria were strongest associated with change in systolic blood pressure. Our proposed CMR sex-specific Groningen-LVH criteria improve the sensitivity to detect LVH, especially in women. Further validation and its association with clinical outcomes is warranted.

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          UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age

          Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
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            Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (CMR) in Caucasians from the UK Biobank population cohort

            Background Cardiovascular magnetic resonance (CMR) is the gold standard method for the assessment of cardiac structure and function. Reference ranges permit differentiation between normal and pathological states. To date, this study is the largest to provide CMR specific reference ranges for left ventricular, right ventricular, left atrial and right atrial structure and function derived from truly healthy Caucasian adults aged 45–74. Methods Five thousand sixty-five UK Biobank participants underwent CMR using steady-state free precession imaging at 1.5 Tesla. Manual analysis was performed for all four cardiac chambers. Participants with non-Caucasian ethnicity, known cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Remaining participants formed the healthy reference cohort; reference ranges were calculated and were stratified by gender and age (45–54, 55–64, 65–74). Results After applying exclusion criteria, 804 (16.2%) participants were available for analysis. Left ventricular (LV) volumes were larger in males compared to females for absolute and indexed values. With advancing age, LV volumes were mostly smaller in both sexes. LV ejection fraction was significantly greater in females compared to males (mean ± standard deviation [SD] of 61 ± 5% vs 58 ± 5%) and remained static with age for both genders. In older age groups, LV mass was lower in men, but remained virtually unchanged in women. LV mass was significantly higher in males compared to females (mean ± SD of 53 ± 9 g/m2 vs 42 ± 7 g/m2). Right ventricular (RV) volumes were significantly larger in males compared to females for absolute and indexed values and were smaller with advancing age. RV ejection fraction was higher with increasing age in females only. Left atrial (LA) maximal volume and stroke volume were significantly larger in males compared to females for absolute values but not for indexed values. LA ejection fraction was similar for both sexes. Right atrial (RA) maximal volume was significantly larger in males for both absolute and indexed values, while RA ejection fraction was significantly higher in females. Conclusions We describe age- and sex-specific reference ranges for the left ventricle, right ventricle and atria in the largest validated normal Caucasian population. Electronic supplementary material The online version of this article (doi:10.1186/s12968-017-0327-9) contains supplementary material, which is available to authorized users.
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              Mechanistic Pathways of Sex Differences in Cardiovascular Disease.

              Major differences between men and women exist in epidemiology, manifestation, pathophysiology, treatment, and outcome of cardiovascular diseases (CVD), such as coronary artery disease, pressure overload, hypertension, cardiomyopathy, and heart failure. Corresponding sex differences have been studied in a number of animal models, and mechanistic investigations have been undertaken to analyze the observed sex differences. We summarize the biological mechanisms of sex differences in CVD focusing on three main areas, i.e., genetic mechanisms, epigenetic mechanisms, as well as sex hormones and their receptors. We discuss relevant subtypes of sex hormone receptors, as well as genomic and nongenomic, activational and organizational effects of sex hormones. We describe the interaction of sex hormones with intracellular signaling relevant for cardiovascular cells and the cardiovascular system. Sex, sex hormones, and their receptors may affect a number of cellular processes by their synergistic action on multiple targets. We discuss in detail sex differences in organelle function and in biological processes. We conclude that there is a need for a more detailed understanding of sex differences and their underlying mechanisms, which holds the potential to design new drugs that target sex-specific cardiovascular mechanisms and affect phenotypes. The comparison of both sexes may lead to the identification of protective or maladaptive mechanisms in one sex that could serve as a novel therapeutic target in one sex or in both.
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                Author and article information

                Contributors
                p.van.der.harst@umcg.nl
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                23 March 2021
                23 March 2021
                2021
                : 11
                : 6662
                Affiliations
                [1 ]GRID grid.4830.f, ISNI 0000 0004 0407 1981, The Department of Cardiology, University Medical Center Groningen, , University of Groningen, ; Hanzeplein 1, 9700 RB Groningen, The Netherlands
                [2 ]GRID grid.4830.f, ISNI 0000 0004 0407 1981, The Department of Epidemiology, University Medical Center Groningen, , University of Groningen, ; Groningen, The Netherlands
                Article
                83137
                10.1038/s41598-021-83137-9
                7988153
                9197c3fc-36dd-48b9-aca3-554adbd74a92
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 May 2020
                : 9 December 2020
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                © The Author(s) 2021

                Uncategorized
                cardiac hypertrophy,risk factors,epidemiology
                Uncategorized
                cardiac hypertrophy, risk factors, epidemiology

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