Prediction of biological age and all-cause mortality by 12-lead electrocardiogram in patients without structural heart disease

Prediction of biological age and all-cause mortality by 12-lead electrocardiogram in patients without structural heart disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Prediction of biological age and all-cause mortality by 12-lead electrocardiogram in patients without structural heart disease Naomi Hirota, Shinya Suzuki, Takuto Arita, Naoharu Yagi, Takayuki Otsuka, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-27441/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Aug, 2021 Read the published version in BMC Geriatrics → Version 1 posted 3 You are reading this latest preprint version Abstract Background: The 12-lead electrocardiogram (ECG) is affected by not only the cardiovascular but also the non-cardiovascular status. Whether ECG can be the determinant of biological age (BA) and the gap between chronological age (CA) and ECG-predicted BA reflect differences in prognosis are unclear. Methods: In the Shinken Database 2010 – 2017 ( n = 19170), 12-lead ECG was analyzed in 13005 patients excluding those with structural heart disease or having pacing beats, atrial or ventricular tachyarrhythmia, and indeterminate axis (R axis > 180˚) on index ECG. The prediction model of BA was developed by principal component analysis with 438 ECG parameters. The gap between ECG-predicted BA and CA was calculated (AgeDiff = ECG-predicted BA − CA). Results: The ECG-predicted BA was significantly correlated with CA (r = 0.967). Patients with a positively wide AgeDiff had a higher incidence of all-cause mortality compared to those with a narrow AgeDiff or those with negative AgeDiff. The risk of AgeDiff > 0 for all-cause mortality compared with AgeDiff ≤ 0 was 1.78 (95%CI: 1.00 − 3.16), which increased according to the aging and became the highest in patients with CA of 71 − 80 years. Conclusion: Our data suggested that 12-lead ECG can be a tool to estimate BA. The gap between ECG-predicted BA and CA allowed estimation of increased risk of all-cause mortality in patients without structural heart disease. Geriatrics & Gerontology electrocardiogram biological age mortality Figures Figure 1 Figure 2 Background Aging is one of the strongest predictors of mortality. However, chronological age (CA) itself might not be a reliable indicator of the functional deterioration because aging is thought to have heterogeneity which are reliant upon a balance between exposure to damaging properties and resiliency. 1, 2 To simply represent the actual status of individual aging, the concept of biological age (BA) have been developed. BA is estimated as a single variable which merged the complex equations for estimating age using multiple biomarkers. For the estimation, various biomarkers are used including physical, physiological, or biochemical parameters which would represent individual health status. 2-4 ECG has been widely recorded to detect or evaluate the risk of cardiac diseases. ECG parameters can be affected by age, gender, and individual physical conditions 5, 6 which are mainly related to the circulatory and the respiratory system. The possible mechanisms underlying these effects have been considered to include changing topography of the heart in relation to the thorax and diaphragm, modification of the constituents of the volume conductor (skin, subcutaneous fat, lung parenchyma), or alterations of cardiac configuration and intracardiac conduction. 5, 7 Aging is one of the most important factors underlying these electrophysiological and electroanatomical changes. 5, 6, 8 There have been several studies that challenged to predict BA or "heart age" using ECG. 9-11 Moreover, it has been reported that there is a discrepancy between BA estimated by ECG and the actual CA, 9 which could be related to individual physical conditions and also various cardiovascular diseases. This concept could be utilized to the simple method of screening for the patient health status, but for actual clinical use, we may have to consider the racial difference in the performance for the prediction models of BA. 11 Moreover, so far, most of the models have developed with only several representative ECG parameters by linear regression model, 10, 12 and in only one report, artificial intelligence modeling was applied. 9 In the present study, we developed a prediction model for BA with hundreds of automatically measured ECG parameters by principal component analysis (PCA) algorithm 4 using a single-center cohort in a Japanese cardiovascular hospital. Methods Study population The Shinken Database includes all patients newly visiting the Cardiovascular Institute, Tokyo, Japan, excluding foreign travelers and patients with active cancer. This single hospital-based database was established in June 2004. Details of this database have been described elsewhere. 13 In the present study, computerized database of ECG was used, which was available since February 2010. Therefore, out of total 32570 patients in the Shinken Database, 19170 patients registered between February 2010 and March 2018 were extracted. After excluding patients with structural heart diseases (n = 4915), patients with age under 20 years or over 90 years (90 years; n = 168), and patients with index ECG showing indeterminate axis (R axis >180˚) (n = 76), pacing beats (n = 102), or atrial or ventricular tachyarrhythmia (n = 1763), the remaining 12837 patients were the target population in the present study. Definition of structural heart disease The definitions of structural heart diseases were as follows: valvular heart disease, moderate or severe stenosis or regurgitation on echocardiography; coronary artery disease, diagnosed on angiography or scintigraphy; and hypertrophic and dilated cardiomyopathy, diagnosed on echocardiography or magnetic resonance imaging [MRI]. Heart failure was diagnosed when the patients had symptoms of New York Heart Association (NYHA) class ≥ 2. Patient follow-up The health status and the incidences of cardiovascular events and mortality were maintained in the database by being linked to the medical records of the hospital, and by study documents of prognosis sent once per year to those who stopped hospital visits or who were referred to other hospitals. In the present study, we included the follow-up data until March 2019, and excluded follow-up data of > 3 years after the initial visit to avoid imbalance of follow-up period among patients due to the different registration years (between 2010 and 2018). Parameters obtained from ECG The 12-lead ECG was recorded for 10 s in the supine position, using a GE ECG machine (GE CardioSoft V6.71 and MAC 5500 HD; GE Healthcare, Chicago, IL) at a sampling rate of 500 Hz, and stored using the MUSE data management system. In the database of the computerized raw data of electrocardiogram with GE system, measurement of 639 parameters was automatically performed. Of these, 201 parameters (9 not lead-specific and 192 [16 × 12 leads] lead-specific) were temporally stored data, including the relative coordinate points (i.e., the start point of P-wave) and calculated values much the same to the original parameters (i.e., among QTc parameters, QTc Calculation [QTc Bazett] was used and QTc Framingham and QTc Fridercia were excluded). After excluding them, remaining 438 parameters (6 not lead-specific and 432 [36 × 12 leads] lead-specific) were used in the analysis (Table 1). Evaluation and Statistical analysis Statistical analyses were carried out using SPSS version 26.0 (IBM, Chicago, IL). In all analyses, P < 0.05 was taken to indicate statistical significance. Categorical and consecutive data are presented as number (%) and mean ± SD. (1) Modeling of biological age (BA) using ECG parameters: BA was modeled using ECG parameters following two steps according to the PCA algorithm. 4 [Step 1] Pre-BA was calculated. In the equation, m indicates the number of principal components, and i indicates their individual orders; n indicates the number of ECG parameters, and j indicates their individual orders; β indicates the coefficient in the PCA; x indicates each ECG parameter; and and sd(x) indicate the average value and the standard deviation of each ECG parameter. The p i was calculated as following formula; p i = (R 2 in an univariable linear regression model with each principal component for CA) / (sum of R 2 in the univariable linear regression models with each principal component for CA). [Step 2] BA was calculated by the following formula: BA = pre-BA × (CA) + + (CA - ) × (1 - B ). In the equation, (CA) and indicate the standard deviation and the average value of CA, and B indicates the standardized coefficient in the univariable linear regression analysis where pre-BA and CA were the dependent and the independent variable, respectively. (2) AgeDiff (gap between BA and CA) and its effect on mortality: AgeDiff was individually calculated as the gap between BA and CA (AgeDiff = BA − CA). Patients were categorized by 3-year ranges of AgeDiff (≤0, 0< to ≤3, 3< to ≤6, 69 years), and the cumulative incidence of total mortality by the AgeDiff categories were plot by the Kaplan-Meyer method. Additionally, patients were categorized by AgeDiff >0 and AgeDiff ≤0, and the hazard ratio of AgeDiff >0 for mortality in reference to AgeDiff ≤0 was evaluated by Cox regression analysis with univariable and multivariable models. Results Patient characteristics The characteristics of 12837 patients are shown in Table 2. The study patients included 6897 males (53.7%) and the mean age was 55.5 ± 15.0 years. Prediction models for BA by ECG parameters Using the 438 ECG parameters, the PCA model for CA was constructed, which consisted of 81 unrotated principal components with corresponding eigen values of ≥ 1.0. About 85.9% of total variance was explained by the 81 principal components. The individual BA was significantly correlated with CA (r = 0.967, p <0.001, Figure 1A). When separated by age categories, the coefficient correlation was 0.805 (p <0.001) in patients under 40 years and 0.508 (p <0.001) in patients over 81 years. The dispersion of AgeDiff was smaller in younger patients and larger in elderly patients (Figure 1B). The number of the deceased patients and their AgeDiff with respect to individual CA were displayed in Table 3. The AgeDiff in total population was higher in the deceased patients; 1.97 ± 7.09 in deceased patients and -0.01 ± 5.81 in alive patients (p = 0.012, Table 3). Prediction of all-cause mortality using BA Distribution of deceased or alive patients according to gender and subgroups of AgeDiff were shown in Table 4. During the median follow-up period of 284.2 days, all-cause death occurred in 17, 12, 10, 7, and 9 patients in the AgeDiff categories of ≤0, 0< to ≤3, 3< to ≤6, 69 years. All-cause mortality in the AgeDiff categories of ≤0, 0< to ≤3, 3< to ≤6, 69 years were 0.4%, 0.5%, 0.5%, 0.5%, 0.6%, 0.1% at 1 year, and 0.8%, 1.4%, 1.5%, 2.0%, and 2.5% at 3 year, respectively (Figure 2). The hazard ratio of AgeDiff >0 for the mortality in reference to AgeDiff ≤0 according to individual CA are shown in Table 5. The incident risk of all-cause mortality in patients with AgeDiff >0 increased according to the aging, and the risk of any death was the highest in CA of 71−80 years. Discussion Major findings In this study, we developed a prediction model for BA using 438 ECG parameters. The BA using ECG was significantly correlated with CA (r = 0.967). The AgeDiff (= BA- CA) in total population was higher in the deceased patients (1.97 ± 7.09) compared with alive patients (-0.01 ± 5.81). Patients with a positively wide AgeDiff had a higher incidence of all-cause mortality compared with those with a positively narrow AgeDiff or negative AgeDiff (2.5% at 3 year in AgeDiff >9 years compared with 0.8% at 3 year in AgeDiff ≤0 years, respectively). The incident risk of all-cause mortality in patients with AgeDiff >0 increased according to the aging, and the risk of all-cause death was the highest in CA of 71−80 years. Clinical implication of gap between ECG-predicted BA and CA There have been a number of recent investigations regarding the prediction of BA using medical records, vital signs and laboratory data, 14 or epigenetic changes. 15 These investigations indicated a gap between predicted BA and actual CA, and the gap was deemed to represent epigenetic age acceleration, because it was shown to be associated with higher risks of all-cause mortality, 16, 17 cardiovascular disease, 15, 18 and cross-sectionally with obesity, 19 earlier menopause, 20 and frailty. 21 ECG, which can be performed readily and repeatedly, and can be analyzed instantly, could be a candidate of a tool for predicting BA, because ECG parameters would vary according to individual age and gender. 5, 6 Although ECG is mainly responsible for the circulatory and the respiratory system, several analyses have revealed that ECG can be affected by various extracardiac diseases: ventricular repolarization was altered by hemodialysis 22 ; prolonged QTc was observed in end-stage liver disease 23, 24 and non-alcoholic fatty liver disease 25 ; ST segment and T wave can be altered in acute cholecystitis 26 ; ST depression, left ventricular hypertrophy, prolonged QTc, and T wave inversion were observed in patients with intracranial hemorrhage 27, 28 and other ECG abnormalities were represented in patients with brain injury and stroke 27 ; higher heart rate, prolonged QTc, and low voltage appeared in patients with thyroid dysfunction. 29 The possible common mechanisms which connects the various systemic health status and ECG would be vascular status and autonomic nerve system, which would possibly be the key pathogenesis that accords aging. In the present study, we developed a model for predicting BA using hundreds of ECG parameters and found that the predicted BA in our model could primarily predict CA well (r = 0.967). This result is in line with previous reports that predicted the heart age with several ECG parameters. 10, 12 Moreover, a relatively large AgeDiff suggested an increased mortality rate, and the risk of all-cause mortality in patients with AgeDiff >0 increased according to the aging. This result is in accordance with previous reports that demonstrated the association between AgeDiff (gap between BA and CA) and mortality. 11 Our data confirmed these results with hundreds of automatically measured ECG parameters in Japanese patients without structural heart diseases. Also, our data suggested that AgeDiff with the method we employed could be one of the promising markers for predicting mortality. Limitations There were several limitations in this study. First, all of the participants were patients who visited a cardiovascular hospital in an urban area. Although the study subjects were patients without constructive heart diseases, it will be necessary to validate the results of this study in larger populations of healthy subjects. Second, we used the parameters measured with a GE-ECG machine. The approach or algorithms to measure the waves may be slightly different between ECG machines from various manufacturers, and revalidation with other ECG machines may be necessary. Third, patient characteristics, such as cardiac anatomical information, comorbidities, concomitant medications, and frailty, were not included in our models. Conclusion We developed a prediction model for BA using 12-lead electrocardiogram parameters in patients without structural heart diseases. This ECG-predicted BA and AgeDiff could be used for prediction of all-cause mortality. Declarations Ethics and informed consent This study was performed in accordance with the ethical norms based on the Declaration of Helsinki (revised in 2013) and Ethical Guidelines for Medical and Health Research Involving Human Subjects (Public Notice of the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labour and Welfare, Japan, issued in 2017). Written informed consent was obtained from all participants. The study protocol was reviewed by the Institutional Review Board of the Cardiovascular Institute. Consent for publication Not applicable. Availability of data and materials Data cannot be shared publicly because of a lack of such description in the study protocol and informed consent. Data are available from the Ethics Review Committee at the Cardiovascular Institute for researchers who meet the criteria for access to confidential data. (contact via the corresponding author). Competing interests Dr. Suzuki received research funding from Mitsubishi Tanabe Pharm, and Daiichi Sankyo. Dr. Yamashita has received research funds and/or lecture fees from Daiichi Sankyo, Bayer Yakuhin, Bristol-Myers Squibb, Pfizer, Nippon Boehringer Ingelheim, Eisai, Mitsubishi Tanabe Pharm, Ono Pharmaceutical, and Toa Eiyo. Funding This study was partially supported by the Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development, AMED (JP17ek0210082). Author's contributions NH, SS, and TY conceives the study concept and study design. NH and SS analyzed the data. All authors collected the data and draft the manuscript. TY checked the analyzed data and the manuscript. All authors approved the final version. Acknowledgments We thank Shiro Ueda and Nobuko Ueda at Medical Edge Company, Ltd., for assembling the database by the Clinical Study Supporting System and Yurika Hashiguchi, Hiroaki Arai, Takashi Osada, and Hiroshi Nakai for data management and system administration. References Arbeev KG, Ukraintseva SV and Yashin AI. Dynamics of biomarkers in relation to aging and mortality. Mech Ageing Dev . 2016;156:42-54. Levine ME. Modeling the rate of senescence: can estimated biological age predict mortality more accurately than chronological age? J Gerontol A Biol Sci Med Sci . 2013;68:667-74. Park J, Cho B, Kwon H and Lee C. Developing a biological age assessment equation using principal component analysis and clinical biomarkers of aging in Korean men. Arch Gerontol Geriatr . 2009;49:7-12. Yoo J, Kim Y, Cho ER and Jee SH. Biological age as a useful index to predict seventeen-year survival and mortality in Koreans. BMC Geriatr . 2017;17:7. 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Tayal B, Graff C, Selmer C, Kragholm KH, Kihlstrom M, Nielsen JB, Olsen AS, Pietersen AH, Holst AG, Sogaard P, Christiansen CB, Faber J, Gislason GH, Torp-Pedersen C and Hansen SM. Thyroid dysfunction and electrocardiographic changes in subjects without arrhythmias: a cross-sectional study of primary healthcare subjects from Copenhagen. BMJ Open . 2019;9:e023854. Tables Table 1. List of ECG parameters used in this study. Parameters available in MUSE database system: 639 parameters Parameters used for analysis: 438 parameters (1) Not lead-specific parameters: 6 parameters P-R Interval, P axis, QRS Duration, QTc Calculation (QTc Bazett), R axis, T axis (2) Lead-specific parameters: 432 [36 × 12 leads] parameters ST at J Point, P Area, P' Area, P Area (Full), P Peak Time, P' Peak Time, P Peak Amplitude, P' Peak Amplitude, P Duration, P' Duration, QRS Area, Q Area, Q Peak Amplitude, Q Duration, R Area, R' Area, R Peak Time, R Duration, R' Duration, S Area, S' Area, S Peak Time, S Duration, S' Duration, T Area, T' Area, T Area (Full), T Peak Time, T Peak Amplitude, T' Peak Amplitude, T Duration, T' Duration, Minimum ST level, Max R Amplitude, Maximum ST level, Max S Amplitude Parameters excluded: 201 parameters (1) Not lead-specific parameters: 9 parameters P Onset, P Offset, QRS Count, QTc Framingham, QTc Fridercia, Q-T Interval, Q Onset, Q Offset, T Offset (2) Lead-specific parameters: 192 [16 × 12 leads] parameters P Onset Amplitude, QRS Balance, QRS Deflection, QRS Intrinsicoid, Q Peak Time, R' Peak Time, R Peak Amplitude, R' Peak Amplitude, S' Peak Time, S Peak Amplitude, S' Peak Amplitude, T' Peak Time, T End, ST at End ST, ST at Mid ST, Special T P', R', S', and T' indicated the second components of P, R, S and T wave, respectively, which could be positive or negative polarity. Table 2. Patient characteristics Total Male Female n = 12837 Total n = 6897 Alive n = 6863 Deceased n = 34 Total n =5940 Alive n = 5919 Deceased n = 21 Age 55.5 ± 15.0 54.2 ± 14.4 54.1 ± 14.4 70.9 ± 12.1 57.0 ± 15.6 56.9 ± 15.6 70.1 ± 14.1 Male 6897 (53.7) 6897 (53.7) 6863 (53.5) 34 (0.3) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) BMI 23.4 ± 27.0 24.2 ± 4.5 24.2 ± 4.5 23.3 ± 4.1 22.5 ± 39.3 22.5 ± 39.4 22.5 ± 3.5 SBP 125.8 ± 18.5 127.5 ± 16.7 127.5 ± 16.7 125.0 ± 16.9 124.0 ± 20.2 124.0 ± 20.2 131.3 ± 22.0 DBP 75.3 ± 13.8 77.1 ± 11.5 77.1 ± 11.5 71.0 ± 14.0 73.2 ± 15.8 73.2 ± 15.8 74.3 ± 10.3 Heart rate 71.1 ± 12.9 71.2 ± 13.5 71.2 ± 13.4 73.8 ± 17.8 71.0 ± 12.3 71.0 ± 12.3 74.3 ± 17.0 eGFR 74.9 ± 17.7 74.3 ± 17.0 74.5 ± 16.9 57.6 ± 23.0 75.5 ± 18.5 75.6 ± 18.4 62.7 ± 29.2 LVEF 67.8 ± 6.8 66.3 ± 6.6 66.3 ± 6.6 62.8 ± 13.6 69.5 ± 6.5 69.5 ± 6.5 66.1 ± 8.4 Hypertension 4484 (34.9) 2628 (20.5) 2607 (20.3) 21 (0.2) 1856 (14.5) 1845 (14.4) 11 (0.1) Dyslipidemia 2855 (22.2) 1497 (11.7) 1488 (11.6) 9 (0.1) 1358 (10.6) 1353 (10.5) 5 (0.0) Diabetes 923 (7.2) 640 (5.0) 631 (4.9) 9 (0.1) 283 (2.2) 278 (2.2) 5 (0.0) Hyperuricemia 1362 (10.6) 1160 (9.0) 1149 (9.0) 11 (0.1) 202 (1.6) 199 (1.6) 3 (0.0) CKD 1100 (8.6) 617 (4.8) 603 (4.7) 14 (0.1) 483 (3.8) 475 (3.7) 8 (0.1) Anemia (Hb <11 g/dL) 186 (1.4) 55 (0.4) 46 (0.4) 9 (0.1) 131 (1.0) 127 (1.0) 4 (0.0) Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, systolic blood pressure; LVEF, left ventricular ejection fraction; CKD, chronic kidney disease ; Hb, hemoglobin;. Table 3. The number of deceased subjects and their AgeDiff with respect to individual CA CA Total Male Female N AgeDiff N AgeDiff N AgeDiff Alive Total 12782 -0.01 ± 5.81 6863 0.40 ± 5.61 5919 -0.48 ± 6.00 ≤ 40 years 2352 -4.66 ± 4.88 1319 -3.01 ± 4.81 1033 -6.78 ± 4.10 41-50 years 2468 -2.27 ± 4.76 1444 -1.49 ± 4.96 1024 -3.38 ± 4.23 51-60 years 2828 -0.08 ± 4.75 1656 0.21 ± 4.85 1172 -0.48 ± 4.57 61-70 years 2928 2.26 ± 4.99 1519 2.69 ± 5.16 1409 1.80 ± 4.76 71-80 years 1721 4.18 ± 5.01 740 4.45 ± 5.19 981 3.98 ± 4.87 ≥ 81 years 485 5.99 ± 5.35 185 6.05 ± 4.96 300 5.95 ± 5.58 All-cause death Total 55 1.97 ± 7.09 34 3.39 ± 5.16 21 -0.33 ± 9.10 ≤ 40 years 41-50 years 4 -4.58 ± 3.90 2 -1.28 ± 1.28 2 -7.88 ± 0.62 51-60 years 9 -2.62 ± 5.99 6 -0.81 ± 6.06 3 -6.25 ± 4.68 61-70 years 14 1.38 ± 6.73 8 2.21 ± 4.05 6 0.26 ± 9.60 71-80 years 12 4.78 ± 4.56 10 4.13 ± 3.88 2 8.07 ± 8.22 ≥ 81 years 16 4.60 ± 8.14 8 7.96 ± 3.99 8 1.24 ± 10.02 CV death Total 23 0.80 ± 8.64 15 1.77 ± 5.79 8 -1.03 ± 12.71 ≤ 40 years 41-50 years 2 -3.91 ± 5.00 1 -0.37 1 -7.45 51-60 years 6 -4.08 ± 6.25 4 -2.11 ± 6.43 2 -8.03 ± 4.96 61-70 years 3 4.94 ± 8.76 2 -0.12 ± 0.34 1 15.05 71-80 years 7 3.51 ± 5.10 6 1.78 ± 2.47 1 13.88 ≥ 81 years 5 2.26 ± 14.23 2 12.49 ± 3.55 3 -4.56 ± 14.98 Non-CV death Total 32 2.81 ± 5.74 19 4.67 ± 4.35 13 0.10 ± 6.58 ≤ 40 years 41-50 years 2 -5.25 ± 4.34 1 -2.19 1 -8.32 51-60 years 3 0.31 ± 5.13 2 1.80 ± 6.27 1 -2.67 61-70 years 11 0.40 ± 6.22 6 2.99 ± 4.48 5 -2.70 ± 7.04 71-80 years 5 6.57 ± 3.38 4 7.65 ± 2.73 1 2.26 ≥ 81 years 11 5.66 ± 3.80 6 6.45 ± 2.97 5 4.72 ± 4.80 Table 4. Distribution of deceased or alive subjects according to gender and subgroups of AgeDiff AgeDiff (years) Alive Deceased p-value Total ≤ 0 6435(99.7) 17(0.3) 0.004 0<, ≤ 3 2570(99.5) 12(0.5) 3<, ≤ 6 1951(99.5) 10(0.5) 6<, ≤ 9 1052(99.3) 7(0.7) 9< 774(98.9) 9(1.1) ≤ 0 6435(99.7) 17(0.3) 0.005 0< 6347(99.4) 38(0.6) Male ≤ 0 3268(99.8) 8(0.2) 0.006 0<, ≤ 3 1463(99.5) 7(0.5) 3<, ≤ 6 1118(99.4) 7(0.6) 6<, ≤ 9 571(99.0) 6(1.0) 9< 443(98.7) 6(1.3) ≤ 0 3268(99.8) 8(0.2) 0.005 0< 3595(99.3) 26(0.7) Female 0 ≤ 3167(99.7) 9(0.3) 0.428 0<, ≤ 3 1107(99.6) 5(0.4) 3<, ≤ 6 833(99.6) 3(0.4) 6<, ≤ 9 481(99.8) 1(0.2) 9< 331(99.1) 3(0.9) ≤ 0 3167(99.7) 9(0.3) 0.384 00 compared for those with AgeDiff ≤0 All cause death CV death Non-CV death Total 1.78 (1.00−3.16) 1.32 (0.57−3.05) 2.28 (1.03−5.09) ≤ 40 years 41−50 years 0.03 (0.00−227.84) 0.03 (0.00−9961.22) 0.03 (0.00−8998.6) 51−60 years 0.49 (0.12−1.95) 0.50 (0.09−2.70) 0.47 (0.04−5.23) 61−70 years 1.18 (0.37−3.75) 0.95 (0.09−10.45) 1.25 (0.33−4.72) 71−80 years 2.53 (0.33−19.6) 1.38 (0.17−11.46) 27.69 (0.00−448543.09) ≥ 81 years 1.08 (0.25−4.75) 0.60 (0.07−5.39) 1.56 (0.20−12.19) Abbreviations: CI, confidence interval; Cite Share Download PDF Status: Published Journal Publication published 11 Aug, 2021 Read the published version in BMC Geriatrics → Version 1 posted Editor assigned by journal 31 May, 2020 Submission checks completed at journal 30 May, 2020 Editor invited by journal 30 May, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-27441","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":636216,"identity":"6457940e-9d6e-45f9-b218-f0c363f18164","order_by":0,"name":"Naomi 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07:23:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-27441/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-27441/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12877-021-02391-8","type":"published","date":"2021-08-11T15:22:30+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":1267731,"identity":"f836552c-7284-45a8-83a9-9cd9ef47c1a4","added_by":"auto","created_at":"2020-06-05 20:19:16","extension":"tif","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2435248,"visible":true,"origin":"","legend":"Association between individual BA or AgeDiff and chronological age\n(A) The individual BA was significantly correlated with CA (r = 0.967, p \u003c0.001). (B) The dispersion of AgeDiff was smaller in younger patients and larger in elderly patients.\nBA indicates biological age; CA, chronological age; AgeDiff is defined as ECG-predicted BA − CA.\n\n","description":"","filename":"Figure120200506.tif","url":"https://assets-eu.researchsquare.com/files/rs-27441/v1/Figure120200506.tif"},{"id":1267732,"identity":"b3143972-23f7-4637-a806-54d0196822b0","added_by":"auto","created_at":"2020-06-05 20:19:17","extension":"tif","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1097275,"visible":true,"origin":"","legend":" All-cause mortality by the AgeDiff categories\n\n","description":"","filename":"Figure220200506v2.tif","url":"https://assets-eu.researchsquare.com/files/rs-27441/v1/Figure220200506v2.tif"},{"id":13537791,"identity":"53baa379-2915-4cfd-a53f-f32abf8cd74b","added_by":"auto","created_at":"2021-09-17 01:36:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4460258,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-27441/v1/b8087a09-186b-4fbf-a420-bb6544e8abd2.pdf"}],"financialInterests":"","formattedTitle":"Prediction of biological age and all-cause mortality by 12-lead electrocardiogram in patients without structural heart disease","fulltext":[{"header":"Background","content":"\u003cp\u003eAging is one of the strongest predictors of mortality. However, chronological age (CA) itself might not be a reliable indicator of the functional deterioration because aging is thought to have heterogeneity which are reliant upon a balance between exposure to damaging properties and resiliency.\u003csup\u003e1, 2\u003c/sup\u003e To simply represent the actual status of individual aging, the concept of biological age (BA) have been developed. BA is estimated as a single variable which merged the complex equations for estimating age using multiple biomarkers. For the estimation, various biomarkers are used including physical, physiological, or biochemical parameters which would represent individual health status. \u003csup\u003e2-4\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eECG has been widely recorded to detect or evaluate the risk of cardiac diseases. ECG parameters can be affected by age, gender, and individual physical conditions\u003csup\u003e5, 6\u003c/sup\u003e which are mainly related to the circulatory and the respiratory system. The possible mechanisms underlying these effects have been considered to include changing topography of the heart in relation to the thorax and diaphragm, modification of the constituents of the volume conductor (skin, subcutaneous fat, lung parenchyma), or alterations of cardiac configuration and intracardiac conduction.\u003csup\u003e5, 7\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eAging is one of the most important factors underlying these electrophysiological and electroanatomical changes.\u003csup\u003e5, 6, 8\u003c/sup\u003e There have been several studies that challenged to predict BA or \"heart age\" using ECG.\u003csup\u003e9-11\u003c/sup\u003e Moreover, it has been reported that there is a discrepancy between BA estimated by ECG and the actual CA,\u003csup\u003e9\u003c/sup\u003e which could be related to individual physical conditions and also various cardiovascular diseases. This concept could be utilized to the simple method of screening for the patient health status, but for actual clinical use, we may have to consider the racial difference in the performance for the prediction models of BA.\u003csup\u003e11\u003c/sup\u003e Moreover, so far, most of the models have developed with only several representative ECG parameters by linear regression model,\u003csup\u003e10, 12\u003c/sup\u003e and in only one report, artificial intelligence modeling was applied.\u003csup\u003e9\u003c/sup\u003e In the present study, we developed a prediction model for BA with hundreds of automatically measured ECG parameters by principal component analysis (PCA) algorithm\u003csup\u003e4\u003c/sup\u003e using a single-center cohort in a Japanese cardiovascular hospital.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Shinken Database includes all patients newly visiting the Cardiovascular Institute, Tokyo, Japan, excluding foreign travelers and patients with active cancer. This single hospital-based database was established in June 2004. Details of this database have been described elsewhere.\u003csup\u003e13\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn the present study, computerized database of ECG was used, which was available since February 2010. Therefore, out of total 32570 patients in the Shinken Database, 19170 patients registered between February 2010 and March 2018 were extracted. After excluding patients with structural heart diseases (n = 4915), patients with age under 20 years or over 90 years (\u0026lt;20 or \u0026gt;90 years; n = 168), and patients with index ECG showing indeterminate axis (R axis \u0026gt;180˚) (n = 76), pacing beats (n = 102), or atrial or ventricular tachyarrhythmia (n = 1763), the remaining 12837 patients were the target population in the present study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition of structural heart disease\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe definitions of structural heart diseases were as follows: valvular heart disease, moderate or severe stenosis or regurgitation on echocardiography; coronary artery disease, diagnosed on angiography or scintigraphy; and hypertrophic and dilated cardiomyopathy, diagnosed on echocardiography or magnetic resonance imaging [MRI]. Heart failure was diagnosed when the patients had symptoms of New York Heart Association (NYHA) class \u0026ge; 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient follow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe health status and the incidences of cardiovascular events and mortality were maintained in the database by being linked to the medical records of the hospital, and by study documents of prognosis sent once per year to those who stopped hospital visits or who were referred to other hospitals. In the present study, we included the follow-up data until March 2019, and excluded follow-up data of \u0026gt; 3 years after the initial visit to avoid imbalance of follow-up period among patients due to the different registration years (between 2010 and 2018).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParameters obtained from ECG\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe 12-lead ECG was recorded for 10 s in the supine position, using a GE ECG machine (GE CardioSoft V6.71 and MAC 5500 HD; GE Healthcare, Chicago, IL) at a sampling rate of 500 Hz, and stored using the MUSE data management system.\u003c/p\u003e\n\u003cp\u003eIn the database of the computerized raw data of electrocardiogram with GE system, measurement of 639 parameters was automatically performed. Of these, 201 parameters (9 not lead-specific and 192 [16 \u0026times; 12 leads] lead-specific) were temporally stored data, including the relative coordinate points (i.e., the start point of P-wave) and calculated values much the same to the original parameters (i.e., among QTc parameters, QTc Calculation [QTc Bazett] was used and QTc Framingham and QTc Fridercia were excluded). After excluding them, remaining 438 parameters (6 not lead-specific and 432 [36 \u0026times; 12 leads] lead-specific) were used in the analysis (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEvaluation and Statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were carried out using SPSS version 26.0 (IBM, Chicago, IL). In all analyses, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 was taken to indicate statistical significance. Categorical and consecutive data are presented as number (%) and mean \u0026plusmn; SD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e(1) Modeling of biological age (BA) using ECG parameters: \u003c/em\u003e\u003c/strong\u003eBA was modeled using ECG parameters following two steps according to the PCA algorithm.\u003csup\u003e4\u003c/sup\u003e [Step 1] Pre-BA\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cimg src=\"data:image/png;base64,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\" style=\"width: 178px;\"\u003e\u003c/p\u003e\n\n\u003cp\u003ewas calculated. In the equation, m indicates the number of principal components, and i indicates their individual orders; n indicates the number of ECG parameters, and j indicates their individual orders; \u0026beta; indicates the coefficient in the PCA; \u003cem\u003ex\u003c/em\u003e indicates each ECG parameter; and and \u003cem\u003esd(x)\u003c/em\u003e indicate the average value and the standard deviation of each ECG parameter. The \u003cem\u003ep\u003csub\u003ei\u003c/sub\u003e\u003c/em\u003e was calculated as following formula; \u003cem\u003ep\u003csub\u003ei\u003c/sub\u003e\u003c/em\u003e = (R\u003csup\u003e2\u003c/sup\u003e in an univariable linear regression model with each principal component for CA) / (sum of R\u003csup\u003e2\u003c/sup\u003e in the univariable linear regression models with each principal component for CA). [Step 2] BA was calculated by the following formula: BA = pre-BA \u0026times; (CA) + \u0026nbsp;+ (CA - ) \u0026times; (1 - \u003cem\u003eB\u003c/em\u003e). In the equation, (CA) and \u0026nbsp;indicate the standard deviation and the average value of CA, and \u003cem\u003eB\u003c/em\u003e indicates the standardized coefficient in the univariable linear regression analysis where pre-BA and CA were the dependent and the independent variable, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;(2) AgeDiff (gap between BA and \u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003eCA)\u003cem\u003e and its effect on mortality: \u003c/em\u003e\u003c/strong\u003eAgeDiff was individually calculated as the gap between BA and CA (AgeDiff = BA \u0026minus; CA). Patients were categorized by 3-year ranges of AgeDiff (\u0026le;0, 0\u0026lt; to \u0026le;3, 3\u0026lt; to \u0026le;6, 6\u0026lt; to \u0026le;9, and \u0026gt;9 years), and the cumulative incidence of total mortality by the AgeDiff categories were plot by the Kaplan-Meyer method. Additionally, patients were categorized by AgeDiff \u0026gt;0 and AgeDiff \u0026le;0, and the hazard ratio of AgeDiff \u0026gt;0 for mortality in reference to AgeDiff \u0026le;0 was evaluated by Cox regression analysis with univariable and multivariable models.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe characteristics of 12837 patients are shown in Table 2. The study patients included 6897 males (53.7%) and the mean age was 55.5 \u0026plusmn; 15.0 years.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrediction models for BA by ECG parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing the 438 ECG parameters, the PCA model for CA was constructed, which consisted of 81 unrotated principal components with corresponding eigen values of \u0026ge; 1.0. About 85.9% of total variance was explained by the 81 principal components.\u003c/p\u003e\n\u003cp\u003eThe individual BA was significantly correlated with CA (r = 0.967, p \u0026lt;0.001, Figure 1A). When separated by age categories, the coefficient correlation was 0.805 (p \u0026lt;0.001) in patients under 40 years and 0.508 (p \u0026lt;0.001) in patients over 81 years. The dispersion of AgeDiff was smaller in younger patients and larger in elderly patients (Figure 1B). The number of the deceased patients and their AgeDiff with respect to individual CA were displayed in Table 3. The AgeDiff in total population was higher in the deceased patients; 1.97 \u0026plusmn; 7.09 in deceased patients and -0.01 \u0026plusmn; 5.81 in alive patients (p = 0.012, Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrediction of all-cause mortality using BA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDistribution of deceased or alive patients according to gender and subgroups of AgeDiff were shown in Table 4. During the median follow-up period of 284.2 days, all-cause death occurred in 17, 12, 10, 7, and 9 patients in the AgeDiff categories of \u0026le;0, 0\u0026lt; to \u0026le;3, 3\u0026lt; to \u0026le;6, 6\u0026lt; to \u0026le;9, and \u0026gt;9 years. All-cause mortality in the AgeDiff categories of \u0026le;0, 0\u0026lt; to \u0026le;3, 3\u0026lt; to \u0026le;6, 6\u0026lt; to \u0026le;9, and \u0026gt;9 years were 0.4%, 0.5%, 0.5%, 0.5%, 0.6%, 0.1% at 1 year, and 0.8%, 1.4%, 1.5%, 2.0%, and 2.5% at 3 year, respectively (Figure 2).\u003c/p\u003e\n\u003cp\u003eThe hazard ratio of AgeDiff \u0026gt;0 for the mortality in reference to AgeDiff \u0026le;0 according to individual CA are shown in Table 5. The incident risk of all-cause mortality in patients with AgeDiff \u0026gt;0 increased according to the aging, and the risk of any death was the highest in CA of 71\u0026minus;80 years.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cstrong\u003eMajor findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, we developed a prediction model for BA using 438 ECG parameters. The BA using ECG was significantly correlated with CA (r = 0.967). The AgeDiff (= BA- CA) in total population was higher in the deceased patients (1.97 \u0026plusmn; 7.09) compared with alive patients (-0.01 \u0026plusmn; 5.81). Patients with a positively wide AgeDiff had a higher incidence of all-cause mortality compared with those with a positively narrow AgeDiff or negative AgeDiff (2.5% at 3 year in AgeDiff \u0026gt;9 years compared with 0.8% at 3 year in AgeDiff \u0026le;0 years, respectively). The incident risk of all-cause mortality in patients with AgeDiff \u0026gt;0 increased according to the aging, and the risk of all-cause death was the highest in CA of 71\u0026minus;80 years.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical implication of gap between ECG-predicted BA and CA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere have been a number of recent investigations regarding the prediction of BA using medical records, vital signs and laboratory data,\u003csup\u003e14\u003c/sup\u003e or epigenetic changes.\u003csup\u003e15\u003c/sup\u003e These investigations indicated a gap between predicted BA and actual CA, and the gap was deemed to represent epigenetic age acceleration, because it was shown to be associated with higher risks of all-cause mortality,\u003csup\u003e16, 17\u003c/sup\u003e cardiovascular disease,\u003csup\u003e15, 18\u003c/sup\u003e and cross-sectionally with obesity,\u003csup\u003e19\u003c/sup\u003e earlier menopause,\u003csup\u003e20\u003c/sup\u003e and frailty.\u003csup\u003e21\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eECG, which can be performed readily and repeatedly, and can be analyzed instantly, could be a candidate of a tool for predicting BA, because ECG parameters would vary according to individual age and gender.\u003csup\u003e5, 6\u003c/sup\u003e Although ECG is mainly responsible for the circulatory and the respiratory system, several analyses have revealed that ECG can be affected by various extracardiac diseases: ventricular repolarization was altered by hemodialysis\u003csup\u003e22\u003c/sup\u003e; prolonged QTc was observed in end-stage liver disease\u003csup\u003e23, 24\u003c/sup\u003e and non-alcoholic fatty liver disease\u003csup\u003e25\u003c/sup\u003e; ST segment and T wave can be altered in acute cholecystitis\u003csup\u003e26\u003c/sup\u003e; ST depression, left ventricular hypertrophy, prolonged QTc, and T wave inversion were observed in patients with intracranial hemorrhage\u003csup\u003e27, 28\u003c/sup\u003e and other ECG abnormalities were represented in patients with brain injury and stroke\u003csup\u003e27\u003c/sup\u003e; higher heart rate, prolonged QTc, and low voltage appeared in patients with thyroid dysfunction.\u003csup\u003e29\u003c/sup\u003e The possible common mechanisms which connects the various systemic health status and ECG would be vascular status and autonomic nerve system, which would possibly be the key pathogenesis that accords aging.\u003c/p\u003e\n\u003cp\u003eIn the present study, we developed a model for predicting BA using hundreds of ECG parameters and found that the predicted BA in our model could primarily predict CA well (r = 0.967). This result is in line with previous reports that predicted the heart age with several ECG parameters.\u003csup\u003e10, 12\u003c/sup\u003e Moreover, a relatively large AgeDiff suggested an increased mortality rate, and the risk of all-cause mortality in patients with AgeDiff \u0026gt;0 increased according to the aging. This result is in accordance with previous reports that demonstrated the association between AgeDiff (gap between BA and CA) and mortality.\u003csup\u003e11\u003c/sup\u003e Our data confirmed these results with hundreds of automatically measured ECG parameters in Japanese patients without structural heart diseases. Also, our data suggested that AgeDiff with the method we employed could be one of the promising markers for predicting mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were several limitations in this study. First, all of the participants were patients who visited a cardiovascular hospital in an urban area. Although the study subjects were patients without constructive heart diseases, it will be necessary to validate the results of this study in larger populations of healthy subjects. Second, we used the parameters measured with a GE-ECG machine. The approach or algorithms to measure the waves may be slightly different between ECG machines from various manufacturers, and revalidation with other ECG machines may be necessary. Third, patient characteristics, such as cardiac anatomical information, comorbidities, concomitant medications, and frailty, were not included in our models.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e We developed a prediction model for BA using 12-lead electrocardiogram parameters in patients without structural heart diseases. This ECG-predicted BA and AgeDiff could be used for prediction of all-cause mortality.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics and informed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in accordance with the ethical norms based on the Declaration of Helsinki (revised in 2013) and Ethical Guidelines for Medical and Health Research Involving Human Subjects (Public Notice of the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labour and Welfare, Japan, issued in 2017). Written informed consent was obtained from all participants. The study protocol was reviewed by the Institutional Review Board of the Cardiovascular Institute.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData cannot be shared publicly because of a lack of such description in the study protocol and informed consent. Data are available from the Ethics Review Committee at the Cardiovascular Institute for researchers who meet the criteria for access to confidential data. (contact via the corresponding author).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Suzuki received research funding from Mitsubishi Tanabe Pharm, and Daiichi Sankyo. Dr. Yamashita has received research funds and/or lecture fees from Daiichi Sankyo, Bayer Yakuhin, Bristol-Myers Squibb, Pfizer, Nippon Boehringer Ingelheim, Eisai, Mitsubishi Tanabe Pharm, Ono Pharmaceutical, and Toa Eiyo.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was partially supported by the Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development, AMED (JP17ek0210082).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor's contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNH, SS, and TY conceives the study concept and study design. NH and SS analyzed the data. All authors collected the data and draft the manuscript. TY checked the analyzed data and the manuscript. All authors approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Shiro Ueda and Nobuko Ueda at Medical Edge Company, Ltd., for assembling the database by the Clinical Study Supporting System and Yurika Hashiguchi, Hiroaki Arai, Takashi Osada, and Hiroshi Nakai for data management and system administration.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eArbeev KG, Ukraintseva SV and Yashin AI. Dynamics of biomarkers in relation to aging and mortality. \u003cem\u003eMech Ageing Dev\u003c/em\u003e. 2016;156:42-54.\u003c/li\u003e\n\u003cli\u003eLevine ME. 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Nine-Year Trend of Anticoagulation Use, Thromboembolic Events, and Major Bleeding in Patients With Non-Valvular Atrial Fibrillation- Shinken Database Analysis. \u003cem\u003eCirc J\u003c/em\u003e. 2016;80:639-49.\u003c/li\u003e\n\u003cli\u003eWang Z, Li L, Glicksberg BS, Israel A, Dudley JT and Ma'ayan A. Predicting age by mining electronic medical records with deep learning characterizes differences between chronological and physiological age. \u003cem\u003eJ Biomed Inform\u003c/em\u003e. 2017;76:59-68.\u003c/li\u003e\n\u003cli\u003eRoetker NS, Pankow JS, Bressler J, Morrison AC and Boerwinkle E. Prospective Study of Epigenetic Age Acceleration and Incidence of Cardiovascular Disease Outcomes in the ARIC Study (Atherosclerosis Risk in Communities). \u003cem\u003eCirc Genom Precis Med\u003c/em\u003e. 2018;11:e001937.\u003c/li\u003e\n\u003cli\u003eChen BH, Marioni RE, Colicino E, Peters MJ, Ward-Caviness CK, Tsai PC, Roetker NS, Just AC, Demerath EW, Guan W, Bressler J, Fornage M, Studenski S, Vandiver AR, Moore AZ, Tanaka T, Kiel DP, Liang L, Vokonas P, Schwartz J, Lunetta KL, Murabito JM, Bandinelli S, Hernandez DG, Melzer D, Nalls M, Pilling LC, Price TR, Singleton AB, Gieger C, Holle R, Kretschmer A, Kronenberg F, Kunze S, Linseisen J, Meisinger C, Rathmann W, Waldenberger M, Visscher PM, Shah S, Wray NR, McRae AF, Franco OH, Hofman A, Uitterlinden AG, Absher D, Assimes T, Levine ME, Lu AT, Tsao PS, Hou L, Manson JE, Carty CL, LaCroix AZ, Reiner AP, Spector TD, Feinberg AP, Levy D, Baccarelli A, van Meurs J, Bell JT, Peters A, Deary IJ, Pankow JS, Ferrucci L and Horvath S. DNA methylation-based measures of biological age: meta-analysis predicting time to death. \u003cem\u003eAging (Albany NY)\u003c/em\u003e. 2016;8:1844-1865.\u003c/li\u003e\n\u003cli\u003eMarioni RE, Shah S, McRae AF, Chen BH, Colicino E, Harris SE, Gibson J, Henders AK, Redmond P, Cox SR, Pattie A, Corley J, Murphy L, Martin NG, Montgomery GW, Feinberg AP, Fallin MD, Multhaup ML, Jaffe AE, Joehanes R, Schwartz J, Just AC, Lunetta KL, Murabito JM, Starr JM, Horvath S, Baccarelli AA, Levy D, Visscher PM, Wray NR and Deary IJ. DNA methylation age of blood predicts all-cause mortality in later life. \u003cem\u003eGenome Biol\u003c/em\u003e. 2015;16:25.\u003c/li\u003e\n\u003cli\u003ePerna L, Zhang Y, Mons U, Holleczek B, Saum KU and Brenner H. Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. \u003cem\u003eClin Epigenetics\u003c/em\u003e. 2016;8:64.\u003c/li\u003e\n\u003cli\u003eHorvath S, Erhart W, Brosch M, Ammerpohl O, von Schonfels W, Ahrens M, Heits N, Bell JT, Tsai PC, Spector TD, Deloukas P, Siebert R, Sipos B, Becker T, Rocken C, Schafmayer C and Hampe J. Obesity accelerates epigenetic aging of human liver. \u003cem\u003eProc Natl Acad Sci U S A\u003c/em\u003e. 2014;111:15538-43.\u003c/li\u003e\n\u003cli\u003eLevine ME, Lu AT, Chen BH, Hernandez DG, Singleton AB, Ferrucci L, Bandinelli S, Salfati E, Manson JE, Quach A, Kusters CD, Kuh D, Wong A, Teschendorff AE, Widschwendter M, Ritz BR, Absher D, Assimes TL and Horvath S. Menopause accelerates biological aging. \u003cem\u003eProc Natl Acad Sci U S A\u003c/em\u003e. 2016;113:9327-32.\u003c/li\u003e\n\u003cli\u003eBreitling LP, Saum KU, Perna L, Schottker B, Holleczek B and Brenner H. Frailty is associated with the epigenetic clock but not with telomere length in a German cohort. \u003cem\u003eClin Epigenetics\u003c/em\u003e. 2016;8:21.\u003c/li\u003e\n\u003cli\u003eSivri S and Celik M. Evaluation of index of cardiac-electrophysiological balance before and after hemodialysis in patients with end-stage renal disease. \u003cem\u003eJ Electrocardiol\u003c/em\u003e. 2019;54:72-75.\u003c/li\u003e\n\u003cli\u003eGlowczynska R, Galas M, Oldakowska-Jedynak U, Peller M, Tomaniak M, Raszeja-Wyszomirska J, Milkiewicz P, Krawczyk M, Zieniewicz K and Opolski G. Pretransplant QT Interval: The Relationship with Severity and Etiology of Liver Disease and Prognostic Value After Liver Transplantation. \u003cem\u003eAnn Transplant\u003c/em\u003e. 2018;23:622-630.\u003c/li\u003e\n\u003cli\u003eMoller S, Hove JD, Dixen U and Bendtsen F. New insights into cirrhotic cardiomyopathy. \u003cem\u003eInt J Cardiol\u003c/em\u003e. 2013;167:1101-8.\u003c/li\u003e\n\u003cli\u003eIsmaiel A, Colosi HA, Rusu F and Dumitrascu DL. Cardiac Arrhythmias and Electrocardiogram Modifications in Non-Alcoholic Fatty Liver Disease. A Systematic Review. \u003cem\u003eJ Gastrointestin Liver Dis\u003c/em\u003e. 2019;28:483-493.\u003c/li\u003e\n\u003cli\u003eOzeki M, Takeda Y, Morita H, Miyamura M, Sohmiya K, Hoshiga M and Ishizaka N. Acute cholecystitis mimicking or accompanying cardiovascular disease among Japanese patients hospitalized in a Cardiology Department. \u003cem\u003eBMC Res Notes\u003c/em\u003e. 2015;8:805.\u003c/li\u003e\n\u003cli\u003eKatsanos AH, Korantzopoulos P, Tsivgoulis G, Kyritsis AP, Kosmidou M and Giannopoulos S. Electrocardiographic abnormalities and cardiac arrhythmias in structural brain lesions. \u003cem\u003eInt J Cardiol\u003c/em\u003e. 2013;167:328-34.\u003c/li\u003e\n\u003cli\u003eTakeuchi S, Nagatani K, Otani N, Wada K and Mori K. Electrocardiograph abnormalities in intracerebral hemorrhage. \u003cem\u003eJ Clin Neurosci\u003c/em\u003e. 2015;22:1959-62.\u003c/li\u003e\n\u003cli\u003eTayal B, Graff C, Selmer C, Kragholm KH, Kihlstrom M, Nielsen JB, Olsen AS, Pietersen AH, Holst AG, Sogaard P, Christiansen CB, Faber J, Gislason GH, Torp-Pedersen C and Hansen SM. Thyroid dysfunction and electrocardiographic changes in subjects without arrhythmias: a cross-sectional study of primary healthcare subjects from Copenhagen. \u003cem\u003eBMJ Open\u003c/em\u003e. 2019;9:e023854.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eTable 1. List of ECG parameters used in this study.\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 424.4pt;border: 1pt solid windowtext;padding: 0in 5.4pt;height: 17.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eParameters available in MUSE database system: 639 parameters\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 424.4pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eParameters used for analysis: 438 parameters\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 424.4pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(1) Not lead-specific parameters: 6 parameters\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eP-R Interval, P axis, QRS Duration, QTc Calculation (QTc Bazett), R axis, T axis\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(2) Lead-specific parameters: 432 [36 \u0026times; 12 leads] parameters\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eST at J Point, P Area, P\u0026#39; Area, P Area (Full), P Peak Time, P\u0026#39; Peak Time, P Peak Amplitude, P\u0026#39; Peak Amplitude, P Duration, P\u0026#39; Duration, QRS Area, Q Area, Q Peak Amplitude, Q Duration, R Area, R\u0026#39; Area, R Peak Time, R Duration, R\u0026#39; Duration, S Area, S\u0026#39; Area, S Peak Time, S Duration, S\u0026#39; Duration, T Area, T\u0026#39; Area, T Area (Full), T Peak Time, T Peak Amplitude, T\u0026#39; Peak Amplitude, T Duration, T\u0026#39; Duration, Minimum ST level, Max R Amplitude, Maximum ST level, Max S Amplitude\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 424.4pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eParameters excluded: 201 parameters\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 424.4pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(1) Not lead-specific parameters: 9 parameters\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eP Onset, P Offset, QRS Count, QTc Framingham, QTc Fridercia, Q-T Interval, Q Onset, Q Offset, T Offset\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(2) Lead-specific parameters: 192 [16 \u0026times; 12 leads] parameters\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eP Onset Amplitude, QRS Balance, QRS Deflection, QRS Intrinsicoid, Q Peak Time, R\u0026#39; Peak Time, R Peak Amplitude, R\u0026#39; Peak Amplitude, S\u0026#39; Peak Time, S Peak Amplitude, S\u0026#39; Peak Amplitude, T\u0026#39; Peak Time, T End, ST at End ST, ST at Mid ST, Special T\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eP\u0026#39;, R\u0026#39;, S\u0026#39;, and T\u0026#39; indicated the second components of P, R, S and T wave, respectively, which could be positive or negative polarity.\u003c/span\u003e\u003c/p\u003e\n\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eTable 2. Patient characteristics\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width:637.1pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:81.95pt;border:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Yu Gothic\",sans-serif;color:black;'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:84.45pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:81.95pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Yu Gothic\",sans-serif;color:black;'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003en = 12837\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003en = 6897\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAlive\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003en = 6863\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:84.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eDeceased\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003en = 34\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003en =5940\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAlive\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003en = 5919\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eDeceased\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003en = 21\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:81.95pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAge\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e55.5 \u0026plusmn; 15.0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e54.2 \u0026plusmn; 14.4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e54.1 \u0026plusmn; 14.4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:84.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e70.9 \u0026nbsp;\u0026plusmn; 12.1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e57.0 \u0026plusmn; 15.6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e56.9 \u0026plusmn; 15.6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e70.1 \u0026plusmn; 14.1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:81.95pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e6897 (53.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e6897 (53.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e6863 (53.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:84.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e34 (0.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.0 (0.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.0 (0.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.0 (0.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:81.95pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eBMI\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e23.4 \u0026plusmn; 27.0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e24.2 \u0026plusmn; 4.5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e24.2 \u0026plusmn; 4.5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:84.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e23.3 \u0026plusmn; 4.1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e22.5 \u0026plusmn; 39.3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e22.5 \u0026plusmn; 39.4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp 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Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1362 (10.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1160 (9.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1149 (9.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:84.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e11 (0.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e202 (1.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e199 (1.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e3 (0.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:81.95pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCKD\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1100 (8.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e617 (4.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e603 (4.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:84.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e14 (0.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e483 (3.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e475 (3.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e8 (0.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:81.95pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAnemia (Hb \u0026lt;11 g/dL)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e186 (1.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e55 (0.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e46 (0.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:84.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e9 (0.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e131 (1.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e127 (1.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e4 (0.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#404040;'\u003eAbbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, systolic blood pressure;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;LVEF, left ventricular ejection fraction; CKD, chronic kidney disease\u003cspan style=\"color:#404040;\"\u003e; Hb, hemoglobin;.\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\n\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eTable 3. The number of deceased subjects and their AgeDiff with respect to individual CA\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width:637.65pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:78.55pt;border:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Yu Gothic\",sans-serif;color:black;'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCA\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:83.65pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:78.55pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Yu Gothic\",sans-serif;color:black;'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Yu Gothic\",sans-serif;color:black;'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eN\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAgeDiff\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eN\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAgeDiff\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eN\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:83.65pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAgeDiff\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:78.55pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAlive\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e12782\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 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style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e51-60 years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2828\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e-0.08 \u0026plusmn; 4.75\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1656\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.21 \u0026plusmn; 4.85\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1172\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:83.65pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e-0.48 \u0026plusmn; 4.57\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:78.55pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e61-70 years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2928\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2.26 \u0026plusmn; 4.99\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd 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style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e4.78 \u0026plusmn; 4.56\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e4.13 \u0026plusmn; 3.88\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd 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style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e19\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e4.67 \u0026plusmn; 4.35\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:83.65pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.10 \u0026plusmn; 6.58\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:78.55pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026le;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e40 years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:83.65pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e-5.25 \u0026plusmn; 4.34\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e-2.19\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:83.65pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e-8.32\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:78.55pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e51-60 years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.31 \u0026plusmn; 5.13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1.80 \u0026plusmn; 6.27\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:83.65pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e-2.67\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:78.55pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e61-70 years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.40 \u0026plusmn; 6.22\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2.99 \u0026plusmn; 4.48\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:83.65pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e-2.70 \u0026plusmn; 7.04\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:78.55pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e71-80 years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e6.57 \u0026plusmn; 3.38\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e7.65 \u0026plusmn; 2.73\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:83.65pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2.26\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:78.55pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Yu Gothic\",sans-serif;color:black;'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026ge;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e81\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eyears\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e5.66 \u0026plusmn; 3.80\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:78.45pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e6.45 \u0026plusmn; 2.97\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:83.65pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e4.72 \u0026plusmn; 4.80\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eTable 4. Distribution of deceased or alive subjects according to gender and subgroups of AgeDiff\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width:375.0pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Yu Gothic\",sans-serif;color:black;'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAgeDiff (years)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAlive\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eDeceased\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003ep-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026le;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e6435(99.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e17(0.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.004\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid 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4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e9\u0026lt;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e331(99.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e3(0.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026le;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e3167(99.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e9(0.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.384\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Yu Gothic\",sans-serif;color:black;'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0\u0026lt;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2752(99.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e12(0.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:75.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eTable 5. Hazard ratio for mortality in total subjects according to individual CA for subjects with AgeDiff \u0026gt;0 compared for those with AgeDiff \u003cspan style=\"color:black;\"\u003e\u0026le;0\u003c/span\u003e\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width:472.05pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Yu Gothic\",sans-serif;color:black;'\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:1.75in;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAll cause death\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:132.0pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eCV death\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:139.05pt;border:solid windowtext 1.0pt;border-left:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eNon-CV death\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:1.75in;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1.78 (1.00\u0026minus;3.16)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:132.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1.32 (0.57\u0026minus;3.05)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:139.05pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2.28 (1.03\u0026minus;5.09)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026le;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e40 years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:1.75in;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:132.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:139.05pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e41\u0026minus;50 years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:1.75in;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.03 (0.00\u0026minus;227.84)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:132.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.03 (0.00\u0026minus;9961.22)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:139.05pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.03 (0.00\u0026minus;8998.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e51\u0026minus;60 years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:1.75in;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.49 (0.12\u0026minus;1.95)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:132.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.50 (0.09\u0026minus;2.70)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:139.05pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.47 (0.04\u0026minus;5.23)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e61\u0026minus;70 years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:1.75in;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1.18 (0.37\u0026minus;3.75)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd 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1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1.38 (0.17\u0026minus;11.46)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:139.05pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:20.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e27.69 (0.00\u0026minus;448543.09)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:75.0pt;border:solid windowtext 1.0pt;border-top:none;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026ge;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e81\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eyears\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:1.75in;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1.08 (0.25\u0026minus;4.75)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:132.0pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e0.60 (0.07\u0026minus;5.39)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:139.05pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 4.95pt 0in 4.95pt;height:21.0pt;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e1.56 (0.20\u0026minus;12.19)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:16px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:#404040;'\u003eAbbreviations: CI, confidence interval;\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"electrocardiogram, biological age, mortality","lastPublishedDoi":"10.21203/rs.3.rs-27441/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-27441/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eThe 12-lead electrocardiogram (ECG) is affected by not only the cardiovascular but also the non-cardiovascular status. Whether ECG can be the determinant of biological age (BA) and the gap between chronological age (CA) and ECG-predicted BA reflect differences in prognosis are unclear.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eIn the Shinken Database 2010 \u0026ndash; 2017 (\u003cem\u003en\u003c/em\u003e = 19170), 12-lead ECG was analyzed in 13005 patients excluding those with structural heart disease or having pacing beats, atrial or ventricular tachyarrhythmia, and indeterminate axis (R axis\u0026thinsp;\u0026gt;\u0026thinsp;180˚) on index ECG. The prediction model of BA was developed by principal component analysis with 438 ECG parameters. The gap between ECG-predicted BA and CA was calculated (AgeDiff = ECG-predicted BA \u0026minus; CA).\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eThe ECG-predicted BA was significantly correlated with CA (r = 0.967). Patients with a positively wide AgeDiff had a higher incidence of all-cause mortality compared to those with a narrow AgeDiff or those with negative AgeDiff. The risk of AgeDiff\u0026thinsp;\u0026gt;\u0026thinsp;0 for all-cause mortality compared with AgeDiff\u0026thinsp;\u0026le;\u0026thinsp;0 was 1.78 (95%CI: 1.00\u0026thinsp;\u0026minus;\u0026thinsp;3.16), which increased according to the aging and became the highest in patients with CA of 71\u0026thinsp;\u0026minus;\u0026thinsp;80\u0026nbsp;years.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eOur data suggested that 12-lead ECG can be a tool to estimate BA. The gap between ECG-predicted BA and CA allowed estimation of increased risk of all-cause mortality in patients without structural heart disease.\u003c/p\u003e","manuscriptTitle":"Prediction of biological age and all-cause mortality by 12-lead electrocardiogram in patients without structural heart disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-06-05 20:19:16","doi":"10.21203/rs.3.rs-27441/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2020-05-31T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-05-30T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-05-30T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"208be9ba-16a1-4855-beb5-d4eb739e780d","owner":[],"postedDate":"June 5th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":114537,"name":"Geriatrics \u0026 Gerontology"}],"tags":[],"updatedAt":"2021-08-11T15:22:30+00:00","versionOfRecord":{"articleIdentity":"rs-27441","link":"https://doi.org/10.1186/s12877-021-02391-8","journal":{"identity":"bmc-geriatrics","isVorOnly":false,"title":"BMC Geriatrics"},"publishedOn":"2021-08-11 15:22:30","publishedOnDateReadable":"August 11th, 2021"},"versionCreatedAt":"2020-06-05 20:19:16","video":"","vorDoi":"10.1186/s12877-021-02391-8","vorDoiUrl":"https://doi.org/10.1186/s12877-021-02391-8","workflowStages":[]},"version":"v1","identity":"rs-27441","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-27441","identity":"rs-27441","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}